Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious...Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.展开更多
BACKGROUND Nonfunctional pituitary adenoma is a common type of pituitary adenoma, which can lead to headache, visual field disturbance, and cranial nerve damage due to increased tumor volume. Neuroendoscopic and micro...BACKGROUND Nonfunctional pituitary adenoma is a common type of pituitary adenoma, which can lead to headache, visual field disturbance, and cranial nerve damage due to increased tumor volume. Neuroendoscopic and microscopic transsphenoidal approaches have been widely used in the resection of nonfunctional pituitary adenomas. However, the clinical efficacy in neuroendoscopic and microscopic surgery is still controversial. AIM To explore the clinical efficacy of neuroendoscopic and microscopic transsphenoidal approach for resection of nonfunctional pituitary adenomas. METHODS We retrospectively analyzed 251 patients with nonfunctional pituitary adenomas;138 underwent neuroendoscopic surgery via transsphenoidal approach, and 113 underwent microscopic surgery via transsphenoidal approach between July 2010 and September 2015. All patients were followed up for > 6 mo. Gender, age, course of disease, tumor diameter, tumor location, and percentage of patients with headache, visual impairment, sexual dysfunction, and menstrual disorders were contrasted between the two groups to compare the difference of preoperative data. Cure rate, symptom improvement rate, recurrence rate, the postoperative hospital stay, operating time, intraoperative blood loss, and the incidence of postoperative complications were compared in order to evaluate the advantages and disadvantages of neuroendoscopic and microscopic surgery.RESULTS There was no significant difference in cure rate, symptom improvement rate, and recurrence rate between neuroendoscopy group and microscopy group (82.6% vs 85.8%, P > 0.05;90.6% vs 93.8%, P > 0.05;5.1% vs 9.7%, P > 0.05). In the neuroendoscopy group, the postoperative hospital stay was 8.4 ± 0.6 d;operating time was 167.2 ± 9.6 min;intraoperative blood loss was 83.4 ± 9.3 mL, and the rates of diabetes insipidus and electrolyte imbalance were 4.3% and 8.0%, respectively. The corresponding results in the microscopic group were 11.2 ± 0.6 d, 199.7 ± 9.3 min, 138.8 ± 13.6 mL, and 32.7% and 20.4%, respectively. There were significant differences in postoperative hospital stay, operating time, intraoperative blood loss, and the rates of diabetes insipidus and electrolyte imbalance between the two groups (P < 0.05). CONCLUSION Neuroendoscopic and microscopic transsphenoidal approaches have similar clinical efficacy for the resection of nonfunctional pituitary adenomas. Neuroendoscopic surgery reduces operating time, intraoperative bleeding, postoperative recovery, and complications.展开更多
Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have...Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.展开更多
The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurre...The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurrence and development of Parkinson’s disease.However,it remains unclear whether oxidative stress induces Parkinson’s disease through the MHC-I pathway.In the present study,polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium(MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease mouse model.The findings revealed that MHC-I was expressed in both models.To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells,immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8(CD8)+T cell infiltration in the substantia nigra of MPTP-treated mice.The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+T cells.Moreover,in MPTP-induced Parkinson’s disease model mice,the genetic knockdown of endogenous MHC-I,which was caused by injecting specific adenovirus into the substantia nigra,led to a significant reduction in CD8+T cell infiltration and alleviated dopaminergic neuronal death.To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation,the expression of PTEN-induced kinase 1(PINK1)was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA(siRNA),and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells.Taken together,MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation,thus rendering dopaminergic neurons susceptible to immune cells and degeneration.This may be one of the mechanisms of oxidative stress-induced Parkinson’s disease,and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation.All animal experiments were approved by the Southern Medical University Ethics Committee(No.81802040,approved on February 25,2018).展开更多
BACKGROUND Resection of deep intracranial tumors requires significant brain retraction,which frequently causes brain damage.In particular,tumor in the trigone of the lateral ventricular presents a surgical challenge d...BACKGROUND Resection of deep intracranial tumors requires significant brain retraction,which frequently causes brain damage.In particular,tumor in the trigone of the lateral ventricular presents a surgical challenge due to its inaccessible location and intricate adjacent relationships with essential structures such as the optic radiation(OR)fibers.New brain retraction systems have been developed to minimize retraction-associated injury.To date,there is little evidence supporting the superiority of any retraction system in preserving the white matter tract integrity.This report illustrates the initial surgical excision in two patients using a new retraction system termed the cerebral corridor creator(CCC)and demonstrates its advantage in protecting OR fibers.CASE SUMMARY We report two patients with nonspecific symptoms,who had trigone ventricular lesions that involved the neighboring OR identified on preoperative diffusion tensor imaging(DTI).Both patients underwent successful surgical excision using the CCC.Total tumor removal was achieved without additional neurological deficit.DTI showed that the OR fibers were preserved along the surgical field.Preoperative symptoms were alleviated immediately after surgery.Clinical outcomes were improved according to the Glasgow-Outcome-Scale and Activity-of-Daily-Living Scale assessments.CONCLUSION In the two cases,the CCC was a safe and useful tool for creating access to the deep trigonal area while preserving the white matter tract integrity.The CCC is thus a promising alternative brain retractor.展开更多
Excessive theta(θ)frequency oscillation and synchronization in the basal ganglia(BG)has been reported in elderly parkinsonian patients and animal models of levodopa(L-dopa)-induced dyskinesia(LID),particularly theθo...Excessive theta(θ)frequency oscillation and synchronization in the basal ganglia(BG)has been reported in elderly parkinsonian patients and animal models of levodopa(L-dopa)-induced dyskinesia(LID),particularly theθoscillation recorded during periods when L-dopa is withdrawn(the off L-dopa state).To gain insight into processes underlying this activity,we explored the relationship between primary motor cortex(M1)oscillatory activity and BG output in LID.We recorded local field potentials in the substantia nigra pars reticulata(SNr)and M1 of awake,inattentive resting rats before and after L-dopa priming in Sham control,Parkinson disease model,and LID model groups.We found that chronic L-dopa increasedθsynchronization and information flow between the SNr and M1 in off L-dopa state LID rats,with a SNr-to-M1 flow directionality.Compared with the on state,θoscillational activity(θsynchronization and informationflow)during the off state were more closely associated with abnormal involuntary movements.Our findings indicate thatθoscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1θoscillation may participate in the induction of dyskinesia.展开更多
基金supported by the National Natural Science Foundation of China,No.81671125the Natural Science Foundation of Guangdong Province,No.2021A1515011115Guangzhou Science and Technology Project,No.202102010346(all to YZC)。
文摘Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.
文摘BACKGROUND Nonfunctional pituitary adenoma is a common type of pituitary adenoma, which can lead to headache, visual field disturbance, and cranial nerve damage due to increased tumor volume. Neuroendoscopic and microscopic transsphenoidal approaches have been widely used in the resection of nonfunctional pituitary adenomas. However, the clinical efficacy in neuroendoscopic and microscopic surgery is still controversial. AIM To explore the clinical efficacy of neuroendoscopic and microscopic transsphenoidal approach for resection of nonfunctional pituitary adenomas. METHODS We retrospectively analyzed 251 patients with nonfunctional pituitary adenomas;138 underwent neuroendoscopic surgery via transsphenoidal approach, and 113 underwent microscopic surgery via transsphenoidal approach between July 2010 and September 2015. All patients were followed up for > 6 mo. Gender, age, course of disease, tumor diameter, tumor location, and percentage of patients with headache, visual impairment, sexual dysfunction, and menstrual disorders were contrasted between the two groups to compare the difference of preoperative data. Cure rate, symptom improvement rate, recurrence rate, the postoperative hospital stay, operating time, intraoperative blood loss, and the incidence of postoperative complications were compared in order to evaluate the advantages and disadvantages of neuroendoscopic and microscopic surgery.RESULTS There was no significant difference in cure rate, symptom improvement rate, and recurrence rate between neuroendoscopy group and microscopy group (82.6% vs 85.8%, P > 0.05;90.6% vs 93.8%, P > 0.05;5.1% vs 9.7%, P > 0.05). In the neuroendoscopy group, the postoperative hospital stay was 8.4 ± 0.6 d;operating time was 167.2 ± 9.6 min;intraoperative blood loss was 83.4 ± 9.3 mL, and the rates of diabetes insipidus and electrolyte imbalance were 4.3% and 8.0%, respectively. The corresponding results in the microscopic group were 11.2 ± 0.6 d, 199.7 ± 9.3 min, 138.8 ± 13.6 mL, and 32.7% and 20.4%, respectively. There were significant differences in postoperative hospital stay, operating time, intraoperative blood loss, and the rates of diabetes insipidus and electrolyte imbalance between the two groups (P < 0.05). CONCLUSION Neuroendoscopic and microscopic transsphenoidal approaches have similar clinical efficacy for the resection of nonfunctional pituitary adenomas. Neuroendoscopic surgery reduces operating time, intraoperative bleeding, postoperative recovery, and complications.
基金supported the National Natural Science Foundation of China,No.81974178(to CD).
文摘Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.
基金This work was supported by the National Natural Science Foundation of China,Nos.81671240(to SZZ),81560220(to GHL)the Youth Science Foundation of Jiangxi Province of China,No.20151BAB215014(to GHL)Health and Family Planning Commission of Jiangxi Province of China,No.20195109(to GHL)。
文摘The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurrence and development of Parkinson’s disease.However,it remains unclear whether oxidative stress induces Parkinson’s disease through the MHC-I pathway.In the present study,polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium(MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease mouse model.The findings revealed that MHC-I was expressed in both models.To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells,immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8(CD8)+T cell infiltration in the substantia nigra of MPTP-treated mice.The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+T cells.Moreover,in MPTP-induced Parkinson’s disease model mice,the genetic knockdown of endogenous MHC-I,which was caused by injecting specific adenovirus into the substantia nigra,led to a significant reduction in CD8+T cell infiltration and alleviated dopaminergic neuronal death.To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation,the expression of PTEN-induced kinase 1(PINK1)was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA(siRNA),and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells.Taken together,MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation,thus rendering dopaminergic neurons susceptible to immune cells and degeneration.This may be one of the mechanisms of oxidative stress-induced Parkinson’s disease,and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation.All animal experiments were approved by the Southern Medical University Ethics Committee(No.81802040,approved on February 25,2018).
文摘BACKGROUND Resection of deep intracranial tumors requires significant brain retraction,which frequently causes brain damage.In particular,tumor in the trigone of the lateral ventricular presents a surgical challenge due to its inaccessible location and intricate adjacent relationships with essential structures such as the optic radiation(OR)fibers.New brain retraction systems have been developed to minimize retraction-associated injury.To date,there is little evidence supporting the superiority of any retraction system in preserving the white matter tract integrity.This report illustrates the initial surgical excision in two patients using a new retraction system termed the cerebral corridor creator(CCC)and demonstrates its advantage in protecting OR fibers.CASE SUMMARY We report two patients with nonspecific symptoms,who had trigone ventricular lesions that involved the neighboring OR identified on preoperative diffusion tensor imaging(DTI).Both patients underwent successful surgical excision using the CCC.Total tumor removal was achieved without additional neurological deficit.DTI showed that the OR fibers were preserved along the surgical field.Preoperative symptoms were alleviated immediately after surgery.Clinical outcomes were improved according to the Glasgow-Outcome-Scale and Activity-of-Daily-Living Scale assessments.CONCLUSION In the two cases,the CCC was a safe and useful tool for creating access to the deep trigonal area while preserving the white matter tract integrity.The CCC is thus a promising alternative brain retractor.
基金supported by the National Natural Science Foundation of China(81771210)the Natural Science Foundation of Guangdong Province,China(2015A030313288)。
文摘Excessive theta(θ)frequency oscillation and synchronization in the basal ganglia(BG)has been reported in elderly parkinsonian patients and animal models of levodopa(L-dopa)-induced dyskinesia(LID),particularly theθoscillation recorded during periods when L-dopa is withdrawn(the off L-dopa state).To gain insight into processes underlying this activity,we explored the relationship between primary motor cortex(M1)oscillatory activity and BG output in LID.We recorded local field potentials in the substantia nigra pars reticulata(SNr)and M1 of awake,inattentive resting rats before and after L-dopa priming in Sham control,Parkinson disease model,and LID model groups.We found that chronic L-dopa increasedθsynchronization and information flow between the SNr and M1 in off L-dopa state LID rats,with a SNr-to-M1 flow directionality.Compared with the on state,θoscillational activity(θsynchronization and informationflow)during the off state were more closely associated with abnormal involuntary movements.Our findings indicate thatθoscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1θoscillation may participate in the induction of dyskinesia.
