It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a ...It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a variety of secondary complications, including memory loss, cognitive decline, depression, and Alzheimer's disease. The largescale longitudinal population-based studies indicate that post-trauma depression is highly prevalent in spinal cord injury patients. Yet, few basic studies have been conducted to address the potential molecular mechanisms. One of possible factors underlying the depression is the reduction of adult hippocampal neurogenesis which may come from less physical activity, social isolation, chronic pain, and elevated neuroinflammation after spinal cord injury. However, there is no clear consensus yet. In this review, we will first summarize the alteration of hippocampal neurogenesis post-spinal cord injury. Then, we will discuss possible mechanisms underlie this important spinal cord injury consequence. Finally, we will outline the potential therapeutic options aimed at enhancing hippocampal neurogenesis to ameliorate depression.展开更多
Cost effectiveness has been demonstrated for traditional lumbar discectomy, lumbar laminectomy as well as for instrumented and noninstrumented arthrodesis. While emerging evidence suggests that minimally invasive spin...Cost effectiveness has been demonstrated for traditional lumbar discectomy, lumbar laminectomy as well as for instrumented and noninstrumented arthrodesis. While emerging evidence suggests that minimally invasive spine surgery reduces morbidity, duration of hospitalization, and accelerates return to activites of daily living, data regarding cost effectiveness of these novel techniques is limited. The current study analyzes all available data on minimally invasive techniques for lumbar discectomy, decompression, short-segment fusion and deformity surgery. In general, minimallyinvasive spine procedures appear to hold promise in quicker patient recovery times and earlier return to work. Thus, minimally invasive lumbar spine surgery appears to have the potential to be a cost-effective intervention. Moreover, novel less invasive procedures are less destabilizing and may therefore be utilized in certain indications that traditionally required arthrodesis procedures. However, there is a lack of studies analyzing the economic impact of minimally invasive spine surgery. Future studies are necessary to confirm the durability and further define indications for minimally invasive lumbar spine procedures.展开更多
Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management ...Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.展开更多
As a research paradigAs a research paradigm(1)evaluated measures of animal performance correlated with markers of microglia activation and inflammation as they sought to see the effects of more focused radiation in tw...As a research paradigAs a research paradigm(1)evaluated measures of animal performance correlated with markers of microglia activation and inflammation as they sought to see the effects of more focused radiation in two-month-old male athymic nude rats.The authors used intensity modulated radiation therapy(IMRT)and volumetric modulated展开更多
Cell-based models are a promising tool in deciphering the molecular mechanisms underlying the pathogenesis of neurological disorders as well as aiding in the discovery and development of future drug therapies.The grea...Cell-based models are a promising tool in deciphering the molecular mechanisms underlying the pathogenesis of neurological disorders as well as aiding in the discovery and development of future drug therapies.The greatest challenge is creating cell-based models that encapsulate the vast phenotypic presentations as well as the underlying genotypic etiology of these conditions.In this article,we discuss the recent advancements in cell-based models for understanding the pathophysiology of neurological disorders.We reviewed studies discussing the progression of cell-based models to the advancement of three-dimensional models and organoids that provide a more accurate model of the pathophysiology of neurological disorders in vivo.The better we understand how to create more precise models of the neurological system,the sooner we will be able to create patient-specific models and large libraries of these neurological disorders.While three-dimensional models can be used to discover the linking factors to connect the varying phenotypes,such models will also help to understand the early pathophysiology of these neurological disorders and how they are affected by their environment.The three-dimensional cell models will allow us to create more specific treatments and uncover potentially preventative measures in neurological disorders such as autism spectrum disorder,Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis.展开更多
Evidence-based medicine(EBM) is a common concept among medical practitioners, yet unique challenges arise when EBM is applied to spinal surgery. Due to the relative rarity of certain spinal disorders, and a lack of ma...Evidence-based medicine(EBM) is a common concept among medical practitioners, yet unique challenges arise when EBM is applied to spinal surgery. Due to the relative rarity of certain spinal disorders, and a lack of management equipoise, randomized controlled trials may be difficult to execute. Despite this, responsibility rests with spinal surgeons to design high quality studies in order to justify certain treatment modalities. The authors therefore review the tenets of implementing evidencebased research, through the lens of spinal disorders. The process of EBM begins with asking the correct question.An appropriate study is then designed based on the research question. Understanding study designs allows the spinal surgeon to assess the level of evidence provided.Validated outcome measurements allow clinicians to communicate the success of treatment strategies, and will increase the quality of a given study design. Importantly,one must recognize that the randomized controlled trial is not always the optimal study design for a given research question. Rather, prospective observational cohort studies may be more appropriate in certain circumstances, and would provide superior generalizability. Despite the challenges involved with EBM, it is the future of medicine. These issues surrounding EBM are important for spinal surgeons, as well as health policy makers and editorial boards, to have familiarity.展开更多
Objective:Epidermal growth factor receptor variant III(EGFRvIII)is a constitutively-activated mutation of EGFR that contributes to the malignant progression of glioblastoma multiforme(GBM).Temozolomide(TMZ)is a standa...Objective:Epidermal growth factor receptor variant III(EGFRvIII)is a constitutively-activated mutation of EGFR that contributes to the malignant progression of glioblastoma multiforme(GBM).Temozolomide(TMZ)is a standard chemotherapeutic for GBM,but TMZ treatment benefits are compromised by chemoresistance.This study aimed to elucidate the crucial mechanisms leading to EGFRvIII and TMZ resistance.Methods:CRISPR-Cas13a single-cell RNA-seq was performed to thoroughly mine EGFRvIII function in GBM.Western blot,realtime PCR,flow cytometry,and immunofluorescence were used to determine the chemoresistance role of E2F1 and RAD51-associated protein 1(RAD51AP1).Results:Bioinformatic analysis identified E2F1 as the key transcription factor in EGFRvIII-positive living cells.Bulk RNA-seq analysis revealed that E2F1 is a crucial transcription factor under TMZ treatment.Western blot suggested enhanced expression of E2F1 in EGFRvIII-positive and TMZ-treated glioma cells.Knockdown of E2F1 increased sensitivity to TMZ.Venn diagram profiling showed that RAD51AP1 is positively correlated with E2F1,mediates TMZ resistance,and has a potential E2F1 binding site on the promoter.Knockdown of RAD51AP1 enhanced the sensitivity of TMZ;however,overexpression of RAD51AP1 was not sufficient to cause chemotherapy resistance in glioma cells.Furthermore,RAD51AP1 did not impact TMZ sensitivity in GBM cells with high O6-methylguanine-DNA methyltransferase(MGMT)expression.The level of RAD51AP1 expression correlated with the survival rate in MGMT-methylated,but not MGMT-unmethylated TMZ-treated GBM patients.Conclusions:Our results suggest that E2F1 is a key transcription factor in EGFRvIII-positive glioma cells and quickly responds to TMZ treatment.RAD51AP1 was shown to be upregulated by E2F1 for DNA double strand break repair.Targeting RAD51AP1 could facilitate achieving an ideal therapeutic effect in MGMT-methylated GBM cells.展开更多
Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery...Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.展开更多
For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein th...For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.展开更多
Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cell...Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cells(SCs),interact with various cells in and around the injury site and are important for debris elimination,repair,and nerve regeneration.Following PNI,Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages.Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair.The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve.In particular,SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers.This mobility increases SC interactions with other cells in the nerve and the exogenous environment,which influence SC behavior post-injury.Following PNI,SCs directly and indirectly interact with other SCs,fibroblasts,and macrophages.In addition,the inter-and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve.This review provides a basic assessment of SC function post-PNI,as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and,ultimately,repair of the injured nerve.展开更多
Objective To retrospectively study clinical features and diagnostic imaging of vasculogeneic pulsatile tinnitus, and the feasibility and efficacy of transvascular interventional treatment for this condition. Methods D...Objective To retrospectively study clinical features and diagnostic imaging of vasculogeneic pulsatile tinnitus, and the feasibility and efficacy of transvascular interventional treatment for this condition. Methods Data from 82 cases of arterial or venous pulsatile tinnitus were reviewed. DSA characteristics and possible pathophysiological mechanisms of pulsatile tinnitus in these cases were studied. Diagnoses in this group included intracranial arterovenous fistula(AVF)(n=3), spontaneous skull base dural AVF(n=16), traumatic carotid-cavernous sinus fistula(n=5), subclavian artery stenosis(n=2), internal carotid artery stenosis(n=3), intracranial arterial stenosis(n=1), kinked and/or elongated vertebrobasilar artery(n=2), venous sinus diverticulum(n=2), venous sinus stenosis on the dominant drainage side(n=46) and occipital sinus stenosis(n=2).Treatments included embolization and stenting using coils, NBCA glue, Balt balloons, self-expansion stents and intracranial micro-stents via either the femoral artery or femoral vein. Results Procedures were successful in all cases with no surgery-related complications. Tinnitus disappeared within 2 days after the procedure in all cases. Follow up duration was 5-36 months. Recurrence occurred in 4 cases of arterial tinnitus within 3 months following the initial procedure, which improved after revision embolization or symptom management. There was no recurrence in venous tinnitus cases following stent plastic or stent-coiling embolization treatments. Conclusions Endovascular intervention provides a new approach to the diagnosis and treatment of intractable pulsatile tinnitus. It is also effective in differentiating and studying other types of tinnitus.展开更多
Intracranial atherosclerotic disease (ICAD) contributes to a significant number of ischemic strokes. There is debate in the recent literature concerning the impact of the location of stenosis in ICAD on outcome. Some ...Intracranial atherosclerotic disease (ICAD) contributes to a significant number of ischemic strokes. There is debate in the recent literature concerning the impact of the location of stenosis in ICAD on outcome. Some reports have suggested that disease processes and outcomes vary by vessel location, potentially altering the natural history and indications for intervention. Here we have performed a comprehensive, critical review of the natural history of ICAD by vessel in an attempt to assess the differences in disease specific to each of the vascular territories. Our assessment concludes that only minor differences exist between patients with different vessels affected in vessel-specific ICAD. We have found that middle cerebral artery disease confers a lower mortality than vessel-specific ICAD in other intracranial vessels, asymptomatic disease follows a more benign course than symptomatic disease, andthat plaque progression or the detection of microemboli on transcranial Doppler may predict poor outcome. Given the expanding indications for treatment of ICAD and rapidly developing endovascular techniques to confront this disease, a thorough understanding of the natural history of ICAD aids the interventional neuroradiologist in determining when to treat and how to predict outcome in this patient population.展开更多
蛋氨酸 adenosyltransferase II (地席 II ) 是在细胞的新陈代谢的关键酶并且从 L 蛋氨酸和 ATP 催化 S-adenosylmethionine (一样) 的形成。正常休息 T 淋巴细胞举办最小的地席 II 活动，而白血病的房间显著地显示出的激活的增殖的 T ...蛋氨酸 adenosyltransferase II (地席 II ) 是在细胞的新陈代谢的关键酶并且从 L 蛋氨酸和 ATP 催化 S-adenosylmethionine (一样) 的形成。正常休息 T 淋巴细胞举办最小的地席 II 活动，而白血病的房间显著地显示出的激活的增殖的 T 淋巴细胞和转变 T 提高了地席 II 活动。这个工作被执行在白血病的 T 房间的幸存检验地席 II 活动和一样的生合成的角色。在一样的层次的地席 II 和结果的减少的抑制提高了 FasL mRNA 和蛋白质的表示，并且导致了圆盘(导致发信号的建筑群的死亡) 有 FADD (联系船边交货的死亡域) 和 procaspase-8 招募的形成，以及 caspase-8 激活的伴随物增加和在 c 扭动的减少铺平。开始船边交货的发信号由地席 II 抑制导致了被观察经由出价劈开连接到 mitochondrial 小径并且最终在这些房间导致增加的 caspase-3 激活和 DNA 破碎。而且，堵住地席 2A mRNA 表示，它编码地席 II 的催化子单元，用一条小介入的 RNA 途径提高了 FasL 表示和房间死亡，验证在 T 白血病的房间的幸存的地席 II 活动的必要性质。展开更多
Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells a...Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18 F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.展开更多
Nafamostat mesylate,an apparent soi-disant panacea of sorts,is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass,mitigate the inflammatory response in patients diagnosed with acut...Nafamostat mesylate,an apparent soi-disant panacea of sorts,is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass,mitigate the inflammatory response in patients diagnosed with acute pancreatitis,and reverse the coagulopathy of patients experiencing the commonly preterminal disseminated intravascular coagulation in the Far East.The serine protease inhibitor nafamostat mesylate exhibits significant neuroprotective effects in the setting of neurovascular ischemia.Nafamostat mesylate generates neuroprotective effects by attenuating the enzymatic activity of serine proteases,neuroinflammatory signaling cascades,and the endoplasmic reticulum stress responses,downregulating excitotoxic transient receptor membrane channel subfamily 7 cationic currents,modulating the activity of intracellular signal transduction pathways,and supporting neuronal survival brain-derived neurotrophic factor/TrkB/ERK1/2/CREB,nuclear factor kappa B.The effects collectively reduce neuronal necrosis and apoptosis and prevent ischemia mediated disruption of blood-brain barrier microarchitecture.Investigational clinical applications of these compounds may mitigate ischemic reperfusion injury in patients undergoing cardiac,hepatic,renal,or intestinal transplant,preventing allograft rejection,and treating solid organ malignancies.Neuroprotective effects mediated by nafamostat mesylate support the wise conduct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.展开更多
Biomaterial bridging provides physical substrates to guide axonal growth across the lesion.To achieve efficient directional guidance,combinatory strategies using permissive matrix,cells and trophic factors are necessa...Biomaterial bridging provides physical substrates to guide axonal growth across the lesion.To achieve efficient directional guidance,combinatory strategies using permissive matrix,cells and trophic factors are necessary.In the present study,we evaluated permissive effect of poly(acrylonitrile-co-vinyl chloride)guidance channels filled by different densities of laminin-precoated unidirectional polypropylene filaments combined with Schwann cells,and glial cell line-derived neurotrophic factor for axonal regeneration through a T10 hemisected spinal cord gap in adult rats.We found that channels with filaments significantly reduced the lesion cavity,astrocytic gliosis,and inflammatory responses at the graft-host boundaries.The laminin coated low density filament provided the most favorable directional guidance for axonal regeneration which was enhanced by co-grafting of Schwann cells and glial cell line-derived neurotrophic factor.These results demonstrate that the combinatorial strategy of filament-filled guiding scaffold,adhesive molecular laminin,Schwann cells,and glial cell line-derived neurotrophic factor,provides optimal topographical cues in stimulating directional axonal regeneration following spinal cord injury.This study was approved by Indiana University Institutional Animal Care and Use Committees(IACUC#:11011)on October 29,2015.展开更多
Background Despite the current availability of flow diverter devices(FDD), problems remains regarding optimal endovascular treatment(EVT) for blood blister-like aneurysms(BBAs) of the internal carotid artery(ICA). Obj...Background Despite the current availability of flow diverter devices(FDD), problems remains regarding optimal endovascular treatment(EVT) for blood blister-like aneurysms(BBAs) of the internal carotid artery(ICA). Objective To evaluate the safety and efficacy of EVT of BBAs in the ICA with a Willis covered stent. Methods 20 consecutive patients(5 men and 15 women) with ruptured BBAs underwent EVT using a Willis covered stent in two institutions from March 2013 to March 2018. Clinical observations, angiographic characteristics, and procedural and follow-up outcomes were retrospectively evaluated. Results 20 consecutive patients(5 men and 15 women) with ruptured BBAs underwent EVT using a Willis covered stent in two institutions from March 2013 to March 2018. Clinical observations, angiographic characteristics, and procedural and follow-up outcomes were retrospectively evaluated. Conclusion Our initial results demonstrate that reconstructive EVT using a Willis covered stent provides a viable approach to treat ICA BBAs. However, an expanded clinical evaluation and larger cohort are needed to confirm the results.展开更多
Spinal cord injury(SCI) results in lesions that destroy tissue and disrupt spinal tracts, producing deficits in locomotor and autonomic function. The majority of treatment strategies after SCI have concentrated on the...Spinal cord injury(SCI) results in lesions that destroy tissue and disrupt spinal tracts, producing deficits in locomotor and autonomic function. The majority of treatment strategies after SCI have concentrated on the damaged spinal cord, for example working to reduce lesion size or spread, or encouraging regrowth of severed descending axonal projections through the lesion, hoping to re-establish synaptic connectivity with caudal targets. In our work, we have focused on a novel target for treatment after SCI, surviving spinal motoneurons and their target musculature, with the hope of developing effective treatments to preserve or restore lost function following SCI. We previously demonstrated that motoneurons, and the muscles they innervate, show pronounced atrophy after SCI. Importantly, SCI-induced atrophy of motoneuron dendrites can be attenuated by treatment with gonadal hormones, testosterone and its active metabolites, estradiol and dihydrotestosterone. Similarly, SCI-induced reductions in muscle fiber cross-sectional areas can be prevented by treatment with androgens. Together, these findings suggest that regressive changes in motoneuron and muscle morphology seen after SCI can be ameliorated by treatment with gonadal hormones, further supporting a role for steroid hormones as neurotherapeutic agents in the injured nervous system.展开更多
While management of appendicular fractures has been well described in the setting of osteopetrosis, there is limited information on managing fractures of the axial spine. Here we present an osteopetrotic patient with ...While management of appendicular fractures has been well described in the setting of osteopetrosis, there is limited information on managing fractures of the axial spine. Here we present an osteopetrotic patient with multiple traumatic multiple, comminuted, unstable cervical spinal fractures managed with non-operative stabilization, and provide a review of the pathophysiology, genetic characteristics, and special considerations that must be explored when determining operative versus non-operative management of spinal injury in osteopetrosis. A PubMed query was performed for English articles in the literature published up to June 2016, and used the following search terms alone and in combination: "osteopetrosis", "spine", "fractures", "osteoclasts", and "operative management". Within four months after initial injury, treatment with halo vest allowed for adequate healing. The patient was asymptomatic with cervical spine dynamic radiographs confirming stability at four months. On four-year follow up examination, the patient remained without neck pain, and CT scan demonstrated partially sclerotic fracture lines with appropriate anatomical alignment. In conclusion, external halo stabilization may be an effective option for treatment of multiple unstable acute traumatic cervical spine fractures in patients with osteopetrosis. Given the challenge of surgical stabilization in osteopetrosis, further research is necessary to elucidate the optimal form of treatment in this select patient population.展开更多
Neuronal injuries such as stroke,traumatic brain injury,and spinal cord injury are leading causes of major disability and death.Chronic therapy for these neuronal injuries requires the promotion of axonal regeneration...Neuronal injuries such as stroke,traumatic brain injury,and spinal cord injury are leading causes of major disability and death.Chronic therapy for these neuronal injuries requires the promotion of axonal regeneration from the remaining neurons(Schwab and Strittmatter,2014).However,the local environment in the central nervous展开更多
基金supported by the Showalter Research Trust Fund (to XG)Indiana Spinal Cord&Brain Injury Research Fund (ISCBIRF) from the Indiana State Departm ent of Health (to XG)。
文摘It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a variety of secondary complications, including memory loss, cognitive decline, depression, and Alzheimer's disease. The largescale longitudinal population-based studies indicate that post-trauma depression is highly prevalent in spinal cord injury patients. Yet, few basic studies have been conducted to address the potential molecular mechanisms. One of possible factors underlying the depression is the reduction of adult hippocampal neurogenesis which may come from less physical activity, social isolation, chronic pain, and elevated neuroinflammation after spinal cord injury. However, there is no clear consensus yet. In this review, we will first summarize the alteration of hippocampal neurogenesis post-spinal cord injury. Then, we will discuss possible mechanisms underlie this important spinal cord injury consequence. Finally, we will outline the potential therapeutic options aimed at enhancing hippocampal neurogenesis to ameliorate depression.
文摘Cost effectiveness has been demonstrated for traditional lumbar discectomy, lumbar laminectomy as well as for instrumented and noninstrumented arthrodesis. While emerging evidence suggests that minimally invasive spine surgery reduces morbidity, duration of hospitalization, and accelerates return to activites of daily living, data regarding cost effectiveness of these novel techniques is limited. The current study analyzes all available data on minimally invasive techniques for lumbar discectomy, decompression, short-segment fusion and deformity surgery. In general, minimallyinvasive spine procedures appear to hold promise in quicker patient recovery times and earlier return to work. Thus, minimally invasive lumbar spine surgery appears to have the potential to be a cost-effective intervention. Moreover, novel less invasive procedures are less destabilizing and may therefore be utilized in certain indications that traditionally required arthrodesis procedures. However, there is a lack of studies analyzing the economic impact of minimally invasive spine surgery. Future studies are necessary to confirm the durability and further define indications for minimally invasive lumbar spine procedures.
基金supported in part by the NIH DA039530(to XJ)a grant from the CURE Epilepsy Foundation(to XJ)
文摘Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.
文摘As a research paradigAs a research paradigm(1)evaluated measures of animal performance correlated with markers of microglia activation and inflammation as they sought to see the effects of more focused radiation in two-month-old male athymic nude rats.The authors used intensity modulated radiation therapy(IMRT)and volumetric modulated
文摘Cell-based models are a promising tool in deciphering the molecular mechanisms underlying the pathogenesis of neurological disorders as well as aiding in the discovery and development of future drug therapies.The greatest challenge is creating cell-based models that encapsulate the vast phenotypic presentations as well as the underlying genotypic etiology of these conditions.In this article,we discuss the recent advancements in cell-based models for understanding the pathophysiology of neurological disorders.We reviewed studies discussing the progression of cell-based models to the advancement of three-dimensional models and organoids that provide a more accurate model of the pathophysiology of neurological disorders in vivo.The better we understand how to create more precise models of the neurological system,the sooner we will be able to create patient-specific models and large libraries of these neurological disorders.While three-dimensional models can be used to discover the linking factors to connect the varying phenotypes,such models will also help to understand the early pathophysiology of these neurological disorders and how they are affected by their environment.The three-dimensional cell models will allow us to create more specific treatments and uncover potentially preventative measures in neurological disorders such as autism spectrum disorder,Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis.
文摘Evidence-based medicine(EBM) is a common concept among medical practitioners, yet unique challenges arise when EBM is applied to spinal surgery. Due to the relative rarity of certain spinal disorders, and a lack of management equipoise, randomized controlled trials may be difficult to execute. Despite this, responsibility rests with spinal surgeons to design high quality studies in order to justify certain treatment modalities. The authors therefore review the tenets of implementing evidencebased research, through the lens of spinal disorders. The process of EBM begins with asking the correct question.An appropriate study is then designed based on the research question. Understanding study designs allows the spinal surgeon to assess the level of evidence provided.Validated outcome measurements allow clinicians to communicate the success of treatment strategies, and will increase the quality of a given study design. Importantly,one must recognize that the randomized controlled trial is not always the optimal study design for a given research question. Rather, prospective observational cohort studies may be more appropriate in certain circumstances, and would provide superior generalizability. Despite the challenges involved with EBM, it is the future of medicine. These issues surrounding EBM are important for spinal surgeons, as well as health policy makers and editorial boards, to have familiarity.
基金supported by the Science and Technology Project of Tianjin Municipal Health Commission(Grant Nos.TJWJ2022MS003 and TJWJ2021ZD008)the Tianjin Science and Technology Plan Project(Grant Nos.21JCYBJC01520 and 20JCYBJC01070)。
文摘Objective:Epidermal growth factor receptor variant III(EGFRvIII)is a constitutively-activated mutation of EGFR that contributes to the malignant progression of glioblastoma multiforme(GBM).Temozolomide(TMZ)is a standard chemotherapeutic for GBM,but TMZ treatment benefits are compromised by chemoresistance.This study aimed to elucidate the crucial mechanisms leading to EGFRvIII and TMZ resistance.Methods:CRISPR-Cas13a single-cell RNA-seq was performed to thoroughly mine EGFRvIII function in GBM.Western blot,realtime PCR,flow cytometry,and immunofluorescence were used to determine the chemoresistance role of E2F1 and RAD51-associated protein 1(RAD51AP1).Results:Bioinformatic analysis identified E2F1 as the key transcription factor in EGFRvIII-positive living cells.Bulk RNA-seq analysis revealed that E2F1 is a crucial transcription factor under TMZ treatment.Western blot suggested enhanced expression of E2F1 in EGFRvIII-positive and TMZ-treated glioma cells.Knockdown of E2F1 increased sensitivity to TMZ.Venn diagram profiling showed that RAD51AP1 is positively correlated with E2F1,mediates TMZ resistance,and has a potential E2F1 binding site on the promoter.Knockdown of RAD51AP1 enhanced the sensitivity of TMZ;however,overexpression of RAD51AP1 was not sufficient to cause chemotherapy resistance in glioma cells.Furthermore,RAD51AP1 did not impact TMZ sensitivity in GBM cells with high O6-methylguanine-DNA methyltransferase(MGMT)expression.The level of RAD51AP1 expression correlated with the survival rate in MGMT-methylated,but not MGMT-unmethylated TMZ-treated GBM patients.Conclusions:Our results suggest that E2F1 is a key transcription factor in EGFRvIII-positive glioma cells and quickly responds to TMZ treatment.RAD51AP1 was shown to be upregulated by E2F1 for DNA double strand break repair.Targeting RAD51AP1 could facilitate achieving an ideal therapeutic effect in MGMT-methylated GBM cells.
基金supported by the Research Foundation of Technology Committee of Tongzhou District,No.KJ2019CX001(to SX).
文摘Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.
基金supported by Hong Kong Spinal Cord Injury Fund (HKSCIF),China (to HZ)。
文摘For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.
基金This work was also supported by the National Natural Science Foundation of China,No.81901365(to WRQ)Jilin Science and Technology Agency Funds in China,Nos.20180101118JC(to RL),20180520115JH(to BPC)and 20190103076JH(to WRQ).
文摘Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cells(SCs),interact with various cells in and around the injury site and are important for debris elimination,repair,and nerve regeneration.Following PNI,Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages.Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair.The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve.In particular,SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers.This mobility increases SC interactions with other cells in the nerve and the exogenous environment,which influence SC behavior post-injury.Following PNI,SCs directly and indirectly interact with other SCs,fibroblasts,and macrophages.In addition,the inter-and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve.This review provides a basic assessment of SC function post-PNI,as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and,ultimately,repair of the injured nerve.
文摘Objective To retrospectively study clinical features and diagnostic imaging of vasculogeneic pulsatile tinnitus, and the feasibility and efficacy of transvascular interventional treatment for this condition. Methods Data from 82 cases of arterial or venous pulsatile tinnitus were reviewed. DSA characteristics and possible pathophysiological mechanisms of pulsatile tinnitus in these cases were studied. Diagnoses in this group included intracranial arterovenous fistula(AVF)(n=3), spontaneous skull base dural AVF(n=16), traumatic carotid-cavernous sinus fistula(n=5), subclavian artery stenosis(n=2), internal carotid artery stenosis(n=3), intracranial arterial stenosis(n=1), kinked and/or elongated vertebrobasilar artery(n=2), venous sinus diverticulum(n=2), venous sinus stenosis on the dominant drainage side(n=46) and occipital sinus stenosis(n=2).Treatments included embolization and stenting using coils, NBCA glue, Balt balloons, self-expansion stents and intracranial micro-stents via either the femoral artery or femoral vein. Results Procedures were successful in all cases with no surgery-related complications. Tinnitus disappeared within 2 days after the procedure in all cases. Follow up duration was 5-36 months. Recurrence occurred in 4 cases of arterial tinnitus within 3 months following the initial procedure, which improved after revision embolization or symptom management. There was no recurrence in venous tinnitus cases following stent plastic or stent-coiling embolization treatments. Conclusions Endovascular intervention provides a new approach to the diagnosis and treatment of intractable pulsatile tinnitus. It is also effective in differentiating and studying other types of tinnitus.
文摘Intracranial atherosclerotic disease (ICAD) contributes to a significant number of ischemic strokes. There is debate in the recent literature concerning the impact of the location of stenosis in ICAD on outcome. Some reports have suggested that disease processes and outcomes vary by vessel location, potentially altering the natural history and indications for intervention. Here we have performed a comprehensive, critical review of the natural history of ICAD by vessel in an attempt to assess the differences in disease specific to each of the vascular territories. Our assessment concludes that only minor differences exist between patients with different vessels affected in vessel-specific ICAD. We have found that middle cerebral artery disease confers a lower mortality than vessel-specific ICAD in other intracranial vessels, asymptomatic disease follows a more benign course than symptomatic disease, andthat plaque progression or the detection of microemboli on transcranial Doppler may predict poor outcome. Given the expanding indications for treatment of ICAD and rapidly developing endovascular techniques to confront this disease, a thorough understanding of the natural history of ICAD aids the interventional neuroradiologist in determining when to treat and how to predict outcome in this patient population.
文摘蛋氨酸 adenosyltransferase II (地席 II ) 是在细胞的新陈代谢的关键酶并且从 L 蛋氨酸和 ATP 催化 S-adenosylmethionine (一样) 的形成。正常休息 T 淋巴细胞举办最小的地席 II 活动，而白血病的房间显著地显示出的激活的增殖的 T 淋巴细胞和转变 T 提高了地席 II 活动。这个工作被执行在白血病的 T 房间的幸存检验地席 II 活动和一样的生合成的角色。在一样的层次的地席 II 和结果的减少的抑制提高了 FasL mRNA 和蛋白质的表示，并且导致了圆盘(导致发信号的建筑群的死亡) 有 FADD (联系船边交货的死亡域) 和 procaspase-8 招募的形成，以及 caspase-8 激活的伴随物增加和在 c 扭动的减少铺平。开始船边交货的发信号由地席 II 抑制导致了被观察经由出价劈开连接到 mitochondrial 小径并且最终在这些房间导致增加的 caspase-3 激活和 DNA 破碎。而且，堵住地席 2A mRNA 表示，它编码地席 II 的催化子单元，用一条小介入的 RNA 途径提高了 FasL 表示和房间死亡，验证在 T 白血病的房间的幸存的地席 II 活动的必要性质。
基金supported by a"KRCF National Agenda Project",by an Asan Life Science Institute Grant(12-241)from the Asan Medical Center,Seoul,Korea
文摘Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18 F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.
文摘Nafamostat mesylate,an apparent soi-disant panacea of sorts,is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass,mitigate the inflammatory response in patients diagnosed with acute pancreatitis,and reverse the coagulopathy of patients experiencing the commonly preterminal disseminated intravascular coagulation in the Far East.The serine protease inhibitor nafamostat mesylate exhibits significant neuroprotective effects in the setting of neurovascular ischemia.Nafamostat mesylate generates neuroprotective effects by attenuating the enzymatic activity of serine proteases,neuroinflammatory signaling cascades,and the endoplasmic reticulum stress responses,downregulating excitotoxic transient receptor membrane channel subfamily 7 cationic currents,modulating the activity of intracellular signal transduction pathways,and supporting neuronal survival brain-derived neurotrophic factor/TrkB/ERK1/2/CREB,nuclear factor kappa B.The effects collectively reduce neuronal necrosis and apoptosis and prevent ischemia mediated disruption of blood-brain barrier microarchitecture.Investigational clinical applications of these compounds may mitigate ischemic reperfusion injury in patients undergoing cardiac,hepatic,renal,or intestinal transplant,preventing allograft rejection,and treating solid organ malignancies.Neuroprotective effects mediated by nafamostat mesylate support the wise conduct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.
基金Research in the Xu laboratory is supported by NIH 1R01100531,1R01 NS103481Merit Review Award I01 BX002356,I01 BX003705,I01 RX002687 from the U.S.Department of Veterans AffairsMari Hulman George Endowment Funds.
文摘Biomaterial bridging provides physical substrates to guide axonal growth across the lesion.To achieve efficient directional guidance,combinatory strategies using permissive matrix,cells and trophic factors are necessary.In the present study,we evaluated permissive effect of poly(acrylonitrile-co-vinyl chloride)guidance channels filled by different densities of laminin-precoated unidirectional polypropylene filaments combined with Schwann cells,and glial cell line-derived neurotrophic factor for axonal regeneration through a T10 hemisected spinal cord gap in adult rats.We found that channels with filaments significantly reduced the lesion cavity,astrocytic gliosis,and inflammatory responses at the graft-host boundaries.The laminin coated low density filament provided the most favorable directional guidance for axonal regeneration which was enhanced by co-grafting of Schwann cells and glial cell line-derived neurotrophic factor.These results demonstrate that the combinatorial strategy of filament-filled guiding scaffold,adhesive molecular laminin,Schwann cells,and glial cell line-derived neurotrophic factor,provides optimal topographical cues in stimulating directional axonal regeneration following spinal cord injury.This study was approved by Indiana University Institutional Animal Care and Use Committees(IACUC#:11011)on October 29,2015.
基金financially supported by the National Natural Scientific Fund of China(grant number 81771951)the Science and Technology Commission of Shanghai(grant number 14DZ1941204)
文摘Background Despite the current availability of flow diverter devices(FDD), problems remains regarding optimal endovascular treatment(EVT) for blood blister-like aneurysms(BBAs) of the internal carotid artery(ICA). Objective To evaluate the safety and efficacy of EVT of BBAs in the ICA with a Willis covered stent. Methods 20 consecutive patients(5 men and 15 women) with ruptured BBAs underwent EVT using a Willis covered stent in two institutions from March 2013 to March 2018. Clinical observations, angiographic characteristics, and procedural and follow-up outcomes were retrospectively evaluated. Results 20 consecutive patients(5 men and 15 women) with ruptured BBAs underwent EVT using a Willis covered stent in two institutions from March 2013 to March 2018. Clinical observations, angiographic characteristics, and procedural and follow-up outcomes were retrospectively evaluated. Conclusion Our initial results demonstrate that reconstructive EVT using a Willis covered stent provides a viable approach to treat ICA BBAs. However, an expanded clinical evaluation and larger cohort are needed to confirm the results.
基金supported by grants from Indiana Spinal Cord and Brain Injury Research Fund(ISCBIRF)by IU’s Office of the Vice Provost for Research through the Faculty Research Support Program to DRS+3 种基金NIH R01 NS103481,R01 NS100531Department of Veterans Affairs I01 RX002356,I01 BX003705Craig H Neilsen Foundation 296749,Indiana Department of Health 019919,ISCBIRFMari Hulman George Endowment Fund to XMX
文摘Spinal cord injury(SCI) results in lesions that destroy tissue and disrupt spinal tracts, producing deficits in locomotor and autonomic function. The majority of treatment strategies after SCI have concentrated on the damaged spinal cord, for example working to reduce lesion size or spread, or encouraging regrowth of severed descending axonal projections through the lesion, hoping to re-establish synaptic connectivity with caudal targets. In our work, we have focused on a novel target for treatment after SCI, surviving spinal motoneurons and their target musculature, with the hope of developing effective treatments to preserve or restore lost function following SCI. We previously demonstrated that motoneurons, and the muscles they innervate, show pronounced atrophy after SCI. Importantly, SCI-induced atrophy of motoneuron dendrites can be attenuated by treatment with gonadal hormones, testosterone and its active metabolites, estradiol and dihydrotestosterone. Similarly, SCI-induced reductions in muscle fiber cross-sectional areas can be prevented by treatment with androgens. Together, these findings suggest that regressive changes in motoneuron and muscle morphology seen after SCI can be ameliorated by treatment with gonadal hormones, further supporting a role for steroid hormones as neurotherapeutic agents in the injured nervous system.
文摘While management of appendicular fractures has been well described in the setting of osteopetrosis, there is limited information on managing fractures of the axial spine. Here we present an osteopetrotic patient with multiple traumatic multiple, comminuted, unstable cervical spinal fractures managed with non-operative stabilization, and provide a review of the pathophysiology, genetic characteristics, and special considerations that must be explored when determining operative versus non-operative management of spinal injury in osteopetrosis. A PubMed query was performed for English articles in the literature published up to June 2016, and used the following search terms alone and in combination: "osteopetrosis", "spine", "fractures", "osteoclasts", and "operative management". Within four months after initial injury, treatment with halo vest allowed for adequate healing. The patient was asymptomatic with cervical spine dynamic radiographs confirming stability at four months. On four-year follow up examination, the patient remained without neck pain, and CT scan demonstrated partially sclerotic fracture lines with appropriate anatomical alignment. In conclusion, external halo stabilization may be an effective option for treatment of multiple unstable acute traumatic cervical spine fractures in patients with osteopetrosis. Given the challenge of surgical stabilization in osteopetrosis, further research is necessary to elucidate the optimal form of treatment in this select patient population.
文摘Neuronal injuries such as stroke,traumatic brain injury,and spinal cord injury are leading causes of major disability and death.Chronic therapy for these neuronal injuries requires the promotion of axonal regeneration from the remaining neurons(Schwab and Strittmatter,2014).However,the local environment in the central nervous
