Objective: This study was aimed at identifying predictive factors of complications during vaginal delivery on scarred uterus. Methodology: During 9 months, from October 1st, 2015 to June 30th, 2016, a case control stu...Objective: This study was aimed at identifying predictive factors of complications during vaginal delivery on scarred uterus. Methodology: During 9 months, from October 1st, 2015 to June 30th, 2016, a case control study was carried out at the Yaoundé Gynaeco-Obstetric and Pediatric Hospital. Eighty nine women each with a single scarred uterus who presented with complications during delivery (cases) were compared to eighty nine others who had a successfully trial of scar (control) during the study period. Data were analyzed using the CSPro version 6.0 and SPSS version 20.0 softwares with statistical significance set at P Results: We recruited 2 groups of 89 women, aged 17 to 40 years, with an average age of 29.05 years. The majority of women with complications were married (50.6%) and unemployed (42.8%). Following univariate analysis, predictive factors of complications were: prematurity (OR = 7.4), post-term (OR = 13.7), no history of vaginal delivery on scarred uterus (OR = 4.3), inter-pregnancy spacing period greater than 60 months (five years) (OR = 2.9), History of caesarian delivery indicated for cephalo-pelvic disproportion (OR = 6.6), less than four ante-natal consultations (OR = 3.6), antenatal consultations done in a Health Centre (OR = 2.7), ante-natal follow up conducted by a nurse (OR = 2.4;IC = [1.2 - 4.7]), referral from a different health unit (OR = 4.4, IC = 2.0 - 9.4), a Bishop score less than 7 on admission (OR = 12.4, IC = 5.6 - 27.4), a meconium stained amniotic fluid (OR = 9.9;CI = [3.6 - 26.8]). After logistic regression, the retained factors associated with complications were post-term (aOR = 34.5), absence of vaginal birth after caesarian delivery, (aOR = 11.7), previous caesarean section indicated for cephalo-pelvic disproportion (aOR = 6.1), a bishop score less than 7 (aOR = 12.0), meconium stained amniotic fluid (aOR = 13.6). Conclusion: Predictive factors of complications can help anticipate negative obstetric outcomes.展开更多
Placenta percreta causing second trimester, spontaneous uterine rupture in non high risk women is less frequent and fewer cases have been reported in the literature. We report a case of uterine rupture in second trime...Placenta percreta causing second trimester, spontaneous uterine rupture in non high risk women is less frequent and fewer cases have been reported in the literature. We report a case of uterine rupture in second trimester of pregnancy due to placenta percreta with non specific symptoms in otherwise uncomplicated pregnancy without any high risk factors. This case report describes the case of young woman presenting second gravid with 21 weeks pregnancy with complaints of whole abdomen pain and dysuria. Ultrasonography shows single intrauterine dead fetus;placenta was fundoposterior in upper segment, a hypoechoic area seen below the placenta suggestive of abruption placentae or placenta accreta. Suddenly patient deteriorated in two hours of hospital stay, frank hemoperitoneum detected, emergency laparotomy done, per operatively whole fundal area of uterus became papery thin and cystic on touch, a small rent seen on fundal surface of uterus. The placenta was densely adhered to the fundoposterior aspect of the uterus. Patient had emergency subtotal hysterectomy. This case highlights that placenta percreta is a rare but serious complication of pregnancy which may present in early pregnancy without any associated high risk factors for placenta percreta with unusual symptoms.展开更多
Introduction: Therapeutic conduct for delivery via a scarred uterus is controversial in modern obstetrics. Some authors recommend a ceasarean section. The purpose of this study was to analyse the conduct and prognosis...Introduction: Therapeutic conduct for delivery via a scarred uterus is controversial in modern obstetrics. Some authors recommend a ceasarean section. The purpose of this study was to analyse the conduct and prognosis of delivery via scarred uterus at Souro Sanou Teaching Hospital in Bobo-Dioulasso. Methods: We conducted a descriptive cross-sectional study from January 1 to December 31, 2017. Data were collected from medical, birth, and operating room records. Result: In total, 531 scared uterus deliveries and 5293 deliveries have been recorded in our study;the frequency of deliveries via a scarred uterus was 9.96%. The average age of the patients was 28.02 years old, with extremes of 17 and 44 years. The average parity was 2.34, with extremes of 1 and 8. Patients with a spacing interval between births of at least 24 months accounted for 86.6% of observed patients. Patients with a single scar uterus made up 70.6% of the population. There were 349 (65.73%) patients who had an emergency caesarean section during a previous delivery. The trial of vaginal delivery via a scarred uterus was conducted on 182 patients with a success rate of 89.56%. There was no maternal death. However, we noted 23 foetal deaths (4.33%). Conclusion: More than 50% of parturient women with a single caesarean uterine scar who underwent the uterine test gave birth vaginally in our department. However, like most previous studies on the subject, we recommend vaginal delivery in the presence of a prior caesarean-scarred uterus whenever possible.展开更多
Endoscopic resection(ER)of colorectal polyps has become a daily practice in most endoscopic units providing a colorectal cancer screening program and requires the availability of local experts and high-end endoscopic ...Endoscopic resection(ER)of colorectal polyps has become a daily practice in most endoscopic units providing a colorectal cancer screening program and requires the availability of local experts and high-end endoscopic devices.ER procedures have evolved over the past few years from endoscopic mucosal resection(EMR)to more advanced techniques,such as endoscopic submucosal dissection and endo-scopic full-thickness resection.Complete resection and disease eradication are the ultimate goals of ER-based techniques,and novel devices have been developed to achieve these goals.The EndoRotor®Endoscopic Powered Resection System(Interscope Medical,Inc.,Northbridge,Massachusetts,United States)is one such device.The EndoRotor is a powered resection tool for the removal of alimentary tract mucosa,including post-EMR persistent lesions with scarring,and has both CE Mark and FDA clearance.This review covers available published evidence documenting the usefulness of EndoRotor for the management of recurrent colorectal polyps.展开更多
Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogr...Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.展开更多
We are pleased to announce that“The 11th SCAR Open Science Conference”will take place in Pucón,Chile from 19-23 August 2024,hosted by the Chilean Antarctic Institute.Detailed information at https://www.scar2024...We are pleased to announce that“The 11th SCAR Open Science Conference”will take place in Pucón,Chile from 19-23 August 2024,hosted by the Chilean Antarctic Institute.Detailed information at https://www.scar2024.org/.The 11th SCAR Open Science Conference theme“Antarctic Science:Crossroads for a New Hope”,recognizes the importance of Antarctica as a unique and fragile ecosystem.With increasing concerns about climate change and its impact on the polar regions,this theme aims to highlight the significance of Antarctic research in shaping our understanding of global environmental challenges.By fostering collaboration and knowledge exchange,the SCAR Open Science conference hopes to inspire new solutions and a renewed sense of hope for the future of our planet.展开更多
Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of f...Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.展开更多
Intrauterine adhesion(IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked ang...Intrauterine adhesion(IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2(b FGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of b FGF100 μg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients(2–4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved.Histological study showed blood vessel density increased obviously. Three patients(3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the b FGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.展开更多
Endoscopic full-thickness resection(EFTR)has emerged as a viable technique in the management of mucosal and subepithelial lesions of the gastrointestinal tract(GIT)not amenable to conventional therapeutic approaches.W...Endoscopic full-thickness resection(EFTR)has emerged as a viable technique in the management of mucosal and subepithelial lesions of the gastrointestinal tract(GIT)not amenable to conventional therapeutic approaches.While various devices and techniques have been described for EFTR,a single,combined fullthickness resection and closure device(full-thickness resection device,FTRD system,Ovesco Endoscopy AG,Tuebingen,Germany)has become commercially available in recent years.Initially,the FTRD system was limited to use in the colorectum only.Recently,a modified version of the FTRD has been released for EFTR in the upper GIT as well.This review provides a broad summary of the FTRD,highlighting recent advances and current challenges.展开更多
Background: Delivery in a scarred uterus is nowadays a real problem in Obstetrics practice, due to the inflation in the number of caesarean sections and the non-unanimous attitude of Obstetrics’ teams towards uterine...Background: Delivery in a scarred uterus is nowadays a real problem in Obstetrics practice, due to the inflation in the number of caesarean sections and the non-unanimous attitude of Obstetrics’ teams towards uterine scars. The factors associated with failed vaginal birth attempts after caesarean section (VBAC) are crucial information that would contribute effectively to deciding on the most appropriate mode of delivery for the mother and her fetus. Their identification would enable us to detect pregnant women at high risk of failure to attempt vaginal birth after caesarean section, and thus contribute to reducing the complications associated with this failure. Objective: We will study the factors associated with failure to vaginal delivery trial after caesarean section at the University Clinics of Kinshasa (UCK). Methods: This study will be a cross-sectional descriptive study with analytical aims. The minimum sample size will be 239. Our study population will consist of records of pregnant women with unicatricial uterus who underwent attempted vaginal delivery after caesarean section at UCK from January 2014 to June 2023. Results will be reported as percentage proportion and mean plus or minus standard deviation. Comparison of means between groups will be made using Student’s t-test, and of proportions using Pearson’s Chi-square test. Logistic regression will be used to generate Odds Ratios to measure the strength of association between variables. The test will be statistically significant for a p value 0.05. Data will be collected and processed confidentially and anonymously. Conclusion: This study will identify the factors associated with the failure of attempted vaginal delivery after caesarean section in order to contribute to the reduction of complications related to its failure in our setting. .展开更多
Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein...Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein,microglia were pharmacologically depleted and the effects on the astrocytic response were examined.We further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)pathway.For in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 mice.To deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were sacrificed.Cell proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent Kit.Locomotor function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were determined.For in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia.PLX3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord injury.Microglial depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord injury.RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397.Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes.Importantly,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration.These findings suggest that microglial depletion impaired astrocyte proliferation and astrocytic scar formation,and induced inflammatory diffusion partly by inhibiting STAT3 phosphorylation in astrocytes following spinal cord injury.展开更多
The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have benefi...The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects.In this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic inflammation.This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area.We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia.Moreover,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal sprouting.However,this treatment decreased the formation of neuronal progenitor cells.This study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.展开更多
Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord ...Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury. In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3 K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3 K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3 K/AKT/mTOR pathway.展开更多
Spinal cord injury is one of the leading causes of morbidity and mortality among young adults in many countries including the United States.Difficulty in the regeneration of neurons is one of the main obstacles that l...Spinal cord injury is one of the leading causes of morbidity and mortality among young adults in many countries including the United States.Difficulty in the regeneration of neurons is one of the main obstacles that leave spinal cord injury patients with permanent paralysis in most instances.Recent research has found that preventing acute and subacute secondary cellular damages to the neurons and supporting glial cells can help slow the progression of spinal cord injury pathogenesis,in part by reactivating endogenous regenerative proteins including Noggin that are normally present during spinal cord development.Noggin is a complex protein and natural inhibitor of the multifunctional bone morphogenetic proteins,and its expression is high during spinal cord development and after induction of spinal cord injury.In this review article,we first discuss the change in expression of Noggin during pathogenesis in spinal cord injury.Second,we discuss the current research knowledge about the neuroprotective role of Noggin in preclinical models of spinal cord injury.Lastly,we explain the gap in the knowledge for the use of Noggin in the treatment of spinal cord injury.The results from extensive in vitro and in vivo research have revealed that the therapeutic efficacy of Noggin treatment remains debatable due to its neuroprotective effects observed only in early phases of spinal cord injury but little to no effect on altering pathogenesis and functional recovery observed in the chronic phase of spinal cord injury.Furthermore,clinical information regarding the role of Noggin in the alleviation of progression of pathogenesis,its therapeutic efficacy,bioavailability,and safety in human spinal cord injury is still lacking and therefore needs further investigation.展开更多
In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly unders...In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.展开更多
Traumatic brain injuries are serious clinical incidents associated with some of the poorest outcomes in neurological practice.Coupled with the limited regenerative capacity of the brain,this has significant implicatio...Traumatic brain injuries are serious clinical incidents associated with some of the poorest outcomes in neurological practice.Coupled with the limited regenerative capacity of the brain,this has significant implications for patients,carers,and healthcare systems,and the requirement for life-long care in some cases.Clinical treatment currently focuses on limiting the initial neural damage with longterm care/support from multidisciplinary teams.Therapies targeting neuroprotection and neural regeneration are not currently available but are the focus of intensive research.Biomaterial-based interventions are gaining popularity for a range of applications including biomolecule and drug delive ry,and to function as cellular scaffolds.Experimental investigations into the development of such novel therapeutics for traumatic brain injury will be critically underpinned by the availability of appropriate high thro ughput,facile,ethically viable,and pathomimetic biological model systems.This represents a significant challenge for researchers given the pathological complexity of traumatic brain injury.Specifically,there is a concerted post-injury response mounted by multiple neural cell types which includes microglial activation and astroglial scarring with the expression of a range of growth inhibito ry molecules and cytokines in the lesion environment.Here,we review common models used for the study of traumatic brain injury(ranging from live animal models to in vitro systems),focusing on penetrating traumatic brain injury models.We discuss their relative advantages and drawbacks for the developmental testing of biomaterial-based therapies.展开更多
Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protei...Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout(GFAPVIM) mice. However, attenuated glial scar formation in post-stroke in GFAP–/– VIM–/– mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIMmice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.展开更多
After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astr...After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.展开更多
文摘Objective: This study was aimed at identifying predictive factors of complications during vaginal delivery on scarred uterus. Methodology: During 9 months, from October 1st, 2015 to June 30th, 2016, a case control study was carried out at the Yaoundé Gynaeco-Obstetric and Pediatric Hospital. Eighty nine women each with a single scarred uterus who presented with complications during delivery (cases) were compared to eighty nine others who had a successfully trial of scar (control) during the study period. Data were analyzed using the CSPro version 6.0 and SPSS version 20.0 softwares with statistical significance set at P Results: We recruited 2 groups of 89 women, aged 17 to 40 years, with an average age of 29.05 years. The majority of women with complications were married (50.6%) and unemployed (42.8%). Following univariate analysis, predictive factors of complications were: prematurity (OR = 7.4), post-term (OR = 13.7), no history of vaginal delivery on scarred uterus (OR = 4.3), inter-pregnancy spacing period greater than 60 months (five years) (OR = 2.9), History of caesarian delivery indicated for cephalo-pelvic disproportion (OR = 6.6), less than four ante-natal consultations (OR = 3.6), antenatal consultations done in a Health Centre (OR = 2.7), ante-natal follow up conducted by a nurse (OR = 2.4;IC = [1.2 - 4.7]), referral from a different health unit (OR = 4.4, IC = 2.0 - 9.4), a Bishop score less than 7 on admission (OR = 12.4, IC = 5.6 - 27.4), a meconium stained amniotic fluid (OR = 9.9;CI = [3.6 - 26.8]). After logistic regression, the retained factors associated with complications were post-term (aOR = 34.5), absence of vaginal birth after caesarian delivery, (aOR = 11.7), previous caesarean section indicated for cephalo-pelvic disproportion (aOR = 6.1), a bishop score less than 7 (aOR = 12.0), meconium stained amniotic fluid (aOR = 13.6). Conclusion: Predictive factors of complications can help anticipate negative obstetric outcomes.
文摘Placenta percreta causing second trimester, spontaneous uterine rupture in non high risk women is less frequent and fewer cases have been reported in the literature. We report a case of uterine rupture in second trimester of pregnancy due to placenta percreta with non specific symptoms in otherwise uncomplicated pregnancy without any high risk factors. This case report describes the case of young woman presenting second gravid with 21 weeks pregnancy with complaints of whole abdomen pain and dysuria. Ultrasonography shows single intrauterine dead fetus;placenta was fundoposterior in upper segment, a hypoechoic area seen below the placenta suggestive of abruption placentae or placenta accreta. Suddenly patient deteriorated in two hours of hospital stay, frank hemoperitoneum detected, emergency laparotomy done, per operatively whole fundal area of uterus became papery thin and cystic on touch, a small rent seen on fundal surface of uterus. The placenta was densely adhered to the fundoposterior aspect of the uterus. Patient had emergency subtotal hysterectomy. This case highlights that placenta percreta is a rare but serious complication of pregnancy which may present in early pregnancy without any associated high risk factors for placenta percreta with unusual symptoms.
文摘Introduction: Therapeutic conduct for delivery via a scarred uterus is controversial in modern obstetrics. Some authors recommend a ceasarean section. The purpose of this study was to analyse the conduct and prognosis of delivery via scarred uterus at Souro Sanou Teaching Hospital in Bobo-Dioulasso. Methods: We conducted a descriptive cross-sectional study from January 1 to December 31, 2017. Data were collected from medical, birth, and operating room records. Result: In total, 531 scared uterus deliveries and 5293 deliveries have been recorded in our study;the frequency of deliveries via a scarred uterus was 9.96%. The average age of the patients was 28.02 years old, with extremes of 17 and 44 years. The average parity was 2.34, with extremes of 1 and 8. Patients with a spacing interval between births of at least 24 months accounted for 86.6% of observed patients. Patients with a single scar uterus made up 70.6% of the population. There were 349 (65.73%) patients who had an emergency caesarean section during a previous delivery. The trial of vaginal delivery via a scarred uterus was conducted on 182 patients with a success rate of 89.56%. There was no maternal death. However, we noted 23 foetal deaths (4.33%). Conclusion: More than 50% of parturient women with a single caesarean uterine scar who underwent the uterine test gave birth vaginally in our department. However, like most previous studies on the subject, we recommend vaginal delivery in the presence of a prior caesarean-scarred uterus whenever possible.
文摘Endoscopic resection(ER)of colorectal polyps has become a daily practice in most endoscopic units providing a colorectal cancer screening program and requires the availability of local experts and high-end endoscopic devices.ER procedures have evolved over the past few years from endoscopic mucosal resection(EMR)to more advanced techniques,such as endoscopic submucosal dissection and endo-scopic full-thickness resection.Complete resection and disease eradication are the ultimate goals of ER-based techniques,and novel devices have been developed to achieve these goals.The EndoRotor®Endoscopic Powered Resection System(Interscope Medical,Inc.,Northbridge,Massachusetts,United States)is one such device.The EndoRotor is a powered resection tool for the removal of alimentary tract mucosa,including post-EMR persistent lesions with scarring,and has both CE Mark and FDA clearance.This review covers available published evidence documenting the usefulness of EndoRotor for the management of recurrent colorectal polyps.
基金supported by the National Natural Science Foundation of China,No.82073783(to YY)the Natural Science Foundation of Beijing,No.7212160(to YY).
文摘Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.
文摘We are pleased to announce that“The 11th SCAR Open Science Conference”will take place in Pucón,Chile from 19-23 August 2024,hosted by the Chilean Antarctic Institute.Detailed information at https://www.scar2024.org/.The 11th SCAR Open Science Conference theme“Antarctic Science:Crossroads for a New Hope”,recognizes the importance of Antarctica as a unique and fragile ecosystem.With increasing concerns about climate change and its impact on the polar regions,this theme aims to highlight the significance of Antarctic research in shaping our understanding of global environmental challenges.By fostering collaboration and knowledge exchange,the SCAR Open Science conference hopes to inspire new solutions and a renewed sense of hope for the future of our planet.
文摘Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.
基金supported by The Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030505)Jiangsu Provincial Key Medical Center (YXZXB2016004)+3 种基金Key Research and Development Program of Jiangsu Province (BE2016612)National Natural Science Foundation of China (81771526)Excellent Youth Natural Science Foundation of Jiangsu Province (BK20170051)Six Talent Peaks Projects in Jiangsu Province (WSW-074)
文摘Intrauterine adhesion(IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2(b FGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of b FGF100 μg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients(2–4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved.Histological study showed blood vessel density increased obviously. Three patients(3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the b FGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.
文摘Endoscopic full-thickness resection(EFTR)has emerged as a viable technique in the management of mucosal and subepithelial lesions of the gastrointestinal tract(GIT)not amenable to conventional therapeutic approaches.While various devices and techniques have been described for EFTR,a single,combined fullthickness resection and closure device(full-thickness resection device,FTRD system,Ovesco Endoscopy AG,Tuebingen,Germany)has become commercially available in recent years.Initially,the FTRD system was limited to use in the colorectum only.Recently,a modified version of the FTRD has been released for EFTR in the upper GIT as well.This review provides a broad summary of the FTRD,highlighting recent advances and current challenges.
文摘Background: Delivery in a scarred uterus is nowadays a real problem in Obstetrics practice, due to the inflation in the number of caesarean sections and the non-unanimous attitude of Obstetrics’ teams towards uterine scars. The factors associated with failed vaginal birth attempts after caesarean section (VBAC) are crucial information that would contribute effectively to deciding on the most appropriate mode of delivery for the mother and her fetus. Their identification would enable us to detect pregnant women at high risk of failure to attempt vaginal birth after caesarean section, and thus contribute to reducing the complications associated with this failure. Objective: We will study the factors associated with failure to vaginal delivery trial after caesarean section at the University Clinics of Kinshasa (UCK). Methods: This study will be a cross-sectional descriptive study with analytical aims. The minimum sample size will be 239. Our study population will consist of records of pregnant women with unicatricial uterus who underwent attempted vaginal delivery after caesarean section at UCK from January 2014 to June 2023. Results will be reported as percentage proportion and mean plus or minus standard deviation. Comparison of means between groups will be made using Student’s t-test, and of proportions using Pearson’s Chi-square test. Logistic regression will be used to generate Odds Ratios to measure the strength of association between variables. The test will be statistically significant for a p value 0.05. Data will be collected and processed confidentially and anonymously. Conclusion: This study will identify the factors associated with the failure of attempted vaginal delivery after caesarean section in order to contribute to the reduction of complications related to its failure in our setting. .
基金supported by the Natural Science Foundation of Guangdong Province,No.2020A1515010090(to ZLZ)the Science and Technology Project Foundation of Guangzhou City,No.202002030004(to HZ).
文摘Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein,microglia were pharmacologically depleted and the effects on the astrocytic response were examined.We further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)pathway.For in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 mice.To deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were sacrificed.Cell proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent Kit.Locomotor function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were determined.For in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia.PLX3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord injury.Microglial depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord injury.RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397.Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes.Importantly,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration.These findings suggest that microglial depletion impaired astrocyte proliferation and astrocytic scar formation,and induced inflammatory diffusion partly by inhibiting STAT3 phosphorylation in astrocytes following spinal cord injury.
基金supported by MINECO and FEDER funds:ref CPP2021-008855 and RTC-2015-4094-1,Junta de Castilla y León ref.LE025P1 7Neural Therapies SLref.NTDev-01 (all to AFL and JMGO)。
文摘The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects.In this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic inflammation.This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area.We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia.Moreover,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal sprouting.However,this treatment decreased the formation of neuronal progenitor cells.This study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.
基金supported by the National Key R&D Program of China,No.2020YFC2008502 (to QW)the National Natural Science Foundation of China,No. 82172534 (to QW)。
文摘Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury. In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3 K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3 K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3 K/AKT/mTOR pathway.
基金supported by SCIRF-2020 PD-01 from the South Carolina Spinal Cord Injury Research Fund(Columbia,SC,USA)(to SKR).
文摘Spinal cord injury is one of the leading causes of morbidity and mortality among young adults in many countries including the United States.Difficulty in the regeneration of neurons is one of the main obstacles that leave spinal cord injury patients with permanent paralysis in most instances.Recent research has found that preventing acute and subacute secondary cellular damages to the neurons and supporting glial cells can help slow the progression of spinal cord injury pathogenesis,in part by reactivating endogenous regenerative proteins including Noggin that are normally present during spinal cord development.Noggin is a complex protein and natural inhibitor of the multifunctional bone morphogenetic proteins,and its expression is high during spinal cord development and after induction of spinal cord injury.In this review article,we first discuss the change in expression of Noggin during pathogenesis in spinal cord injury.Second,we discuss the current research knowledge about the neuroprotective role of Noggin in preclinical models of spinal cord injury.Lastly,we explain the gap in the knowledge for the use of Noggin in the treatment of spinal cord injury.The results from extensive in vitro and in vivo research have revealed that the therapeutic efficacy of Noggin treatment remains debatable due to its neuroprotective effects observed only in early phases of spinal cord injury but little to no effect on altering pathogenesis and functional recovery observed in the chronic phase of spinal cord injury.Furthermore,clinical information regarding the role of Noggin in the alleviation of progression of pathogenesis,its therapeutic efficacy,bioavailability,and safety in human spinal cord injury is still lacking and therefore needs further investigation.
基金supported by the National Natural Science Foundation of China,Nos.82171456 (to QY),81971229 (to QY)the Natural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0263 (to QY)the Postgraduate Research and Innovation Project of Chongqing,Nos.CYB20151 (to QY),CYS19182 (to YC)。
文摘In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.
基金funded by awards from the EPSRC Doctoral Training Centre in Regenerative Medicine and an NHS bursary。
文摘Traumatic brain injuries are serious clinical incidents associated with some of the poorest outcomes in neurological practice.Coupled with the limited regenerative capacity of the brain,this has significant implications for patients,carers,and healthcare systems,and the requirement for life-long care in some cases.Clinical treatment currently focuses on limiting the initial neural damage with longterm care/support from multidisciplinary teams.Therapies targeting neuroprotection and neural regeneration are not currently available but are the focus of intensive research.Biomaterial-based interventions are gaining popularity for a range of applications including biomolecule and drug delive ry,and to function as cellular scaffolds.Experimental investigations into the development of such novel therapeutics for traumatic brain injury will be critically underpinned by the availability of appropriate high thro ughput,facile,ethically viable,and pathomimetic biological model systems.This represents a significant challenge for researchers given the pathological complexity of traumatic brain injury.Specifically,there is a concerted post-injury response mounted by multiple neural cell types which includes microglial activation and astroglial scarring with the expression of a range of growth inhibito ry molecules and cytokines in the lesion environment.Here,we review common models used for the study of traumatic brain injury(ranging from live animal models to in vitro systems),focusing on penetrating traumatic brain injury models.We discuss their relative advantages and drawbacks for the developmental testing of biomaterial-based therapies.
基金supported by the National Natural Science Foundation of China,No. 82071374Discipline Construction Project of Guangdong Medical University,Nos. 1.13 and 4.1.19+1 种基金College Students Innovative Experimental Project in Guangdong Medical University,Nos. FYDB015, ZCDS001, ZYDB004, ZYDB016, and ZZDI001College Students’ Science and Technology Innovation Training Project,Nos. GDMU2020194, GDMU2020195, GDMU2021021, GDMU2021023, GDMU2021091, GDMU2021111 (all to HFW)。
文摘Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout(GFAPVIM) mice. However, attenuated glial scar formation in post-stroke in GFAP–/– VIM–/– mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIMmice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.
基金supported by the National Natural Science Foundation of China,Nos.82101455(to RYY),31872773(to GC),82001168(to JYP)the Key Research and Development Program(Social Development)of Jiangsu Province,No.BE2020667(to GC)+3 种基金the Foundation of Jiangsu Province,333 Project High-level Talents",No.BRA2020076(to GC)the Nantong Civic Science and Technology Project of China,No.JC2020028(to RYY)the Natural Science Research of Jiangsu Higher Education Institutions of China,No.19KJB310012(to RYY)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.
