General Hospital of the Peoples Liberation Army Chengdu Military Region

China

General Hospital of the Peoples Liberation Army Chengdu Military Region

China

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Gong G.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Hu L.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Liu Y.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Bai S.,General Hospital of the Peoples Liberation Army Chengdu Military Region | And 5 more authors.
International Journal of Molecular Medicine | Year: 2014

Cerebral ischemia/reperfusion (I/R) can induce neuronal death, particularly in the hippocampal formation (HF). Molecular genetic studies have suggested that the activities of the transcription factor, hypoxia-inducible factor-1α (HIF-1α), are closely linked to ischemia-induced neuronal death. However, the mechanisms through which HIF-1α functions remain poorly understood. In this study, primary cortical neurons were subjected to oxygen-glucose deprivation (OGD) to establish a cell model of OGD/reperfusion (RP). HIF-1α mRNA and protein expression was measured by qRT-PCR and western blot analysis. Cell proliferation was detected by MTT assay. Flow cytometric analysis was used to detect cell apoptosis and changes in mitochondrial mass. The expression of LC3-I and LC3-II was examined by western blot analysis. We found that HIF-1α increased cell proliferation and decreased cell apoptosis in our cell model of OGD/RP using cultured neonatal rat cortical neurons. The overexpression of HIF-1α significantly induced changes in mitochondrial mass and mitochondrial autophagy in cortical neurons. Moreover, the inhibition of HIF-1α markedly suppressed cell proliferation and mitochondrial autophagy. We also demonstrated that the HIF-1α-induced mitochondrial autophagy was accompanied by the inhibition of the mTOR pathway. This study provides direct in vitro evidence that HIF-1α overexpression triggers mitochondrial autophagy, thereby increasing neuronal survival. Our results highlight a novel target molecule toward which anti-ischemic neuroprotective effects can be applied.


PubMed | General Hospital of Guangzhou Military Command, General Hospital of the Peoples Liberation Army Chengdu Military Region and PLA Fourth Military Medical University
Type: Journal Article | Journal: International journal of molecular medicine | Year: 2014

Cerebral ischemia/reperfusion (I/R) can induce neuronal death, particularly in the hippocampal formation (HF). Molecular genetic studies have suggested that the activities of the transcription factor, hypoxia-inducible factor-1 (HIF-1), are closely linked to ischemia-induced neuronal death. However, the mechanisms through which HIF-1 functions remain poorly understood. In this study, primary cortical neurons were subjected to oxygenglucose deprivation (OGD) to establish a cell model of OGD/reperfusion (RP). HIF-1 mRNA and protein expression was measured by qRT-PCR and western blot analysis. Cell proliferation was detected by MTT assay. Flow cytometric analysis was used to detect cell apoptosis and changes in mitochondrial mass. The expression of LC3- and LC3- was examined by western blot analysis. We found that HIF-1 increased cell proliferation and decreased cell apoptosis in our cell model of OGD/RP using cultured neonatal rat cortical neurons. The overexpression of HIF-1 significantly induced changes in mitochondrial mass and mitochondrial autophagy in cortical neurons. Moreover, the inhibition of HIF-1 markedly suppressed cell proliferation and mitochondrial autophagy. We also demonstrated that the HIF-1-induced mitochondrial autophagy was accompanied by the inhibition of the mTOR pathway. This study provides direct in vitro evidence that HIF-1 overexpression triggers mitochondrial autophagy, thereby increasing neuronal survival. Our results highlight a novel target molecule toward which anti-ischemic neuroprotective effects can be applied.


Yu S.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Shu H.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Yang T.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Huang H.,General Hospital of the Peoples Liberation Army Chengdu Military Region | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2016

Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5-75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels. Furthermore, the migration of neural precursor cells (NPCs) derived from the subventricular zone (SVZ) toward the sits of injury was perturbed by treatment of NgR antagonist peptide NEP1-40. In vitro analysis showed that the knockdown of NgR by lentivirus-delivered siRNA promoted in axonal regeneration and SVZ-derived neural stem cell/progenitor cell (SVZ-NPCs) adhesion and migration, findings which were similar to the effects of NEP1-40. Taken together, our results indicate an important role for NgR in regulating the physiological processes of SVZ-NPCs. The observation of upregulated Nogo-A/NgR in lesion sites in the NFL model suggest that the effects of the perturbed Nogo-A are a key feature during the development and/or the progression of cortical malformation. © 2016 Elsevier Inc.


Shu H.-F.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Shu H.-F.,Chongqing Medical University | Kuang Y.-Q.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Liu S.-Y.,Chongqing Medical University | And 5 more authors.
Journal of Molecular Neuroscience | Year: 2014

Microgyria is associated with epilepsy and due to developmental disruption of neuronal migration. However, the role of endogenous subventricular zone-derived neural progenitors (SDNPs) in formation and hyperexcitability has not been fully elucidated. Here, we establish a neonatal cortex freeze-lesion (FL) model, which was considered as a model for focal microgyria, and simultaneously label SDNPs by CM-DiI. Morphological investigation showed that SDNPs migrated into FL and differentiated into neuronal and glia cell types, suggesting the involvement of endogenous SDNPs in the formation of FL-induced microgyria. Patch-clamp recordings in CM-DiI positive (CM-DiI+) pyramidal neurons within FL indicated an increase in frequency of spontaneous action potentials, while the resting membrane potential did not differ from the controls. We also found that spontaneous excitatory postsynaptic currents (EPSCs) increased in frequency but not in amplitude compared with controls. The evoked EPSCs showed a significant increase of 10-90 % in rise time and decay time in the CM-DiI+ neurons. Moreover, paired-pulse facilitation was dramatically larger in CM-DiI+ pyramidal neurons. Western blotting data showed that AMPA and NMDA receptors were increased to some extent in the FL cortex compared with controls, and the NMDA/AMPA ratio of eEPSCs at CM-DiI + pyramidal neurons was significantly increased. Taken together, our findings provide novel evidence for the contribution of endogenous SDNPs in the formation and epileptogenicity of FL-induced focal microgyria. © 2013 Springer Science+Business Media.


Shu H.-F.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Yang T.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Yu S.-X.,General Hospital of the Peoples Liberation Army Chengdu Military Region | Huang H.-D.,General Hospital of the Peoples Liberation Army Chengdu Military Region | And 3 more authors.
PLoS ONE | Year: 2014

Background: Although some trials assessed the effectiveness of aerobic exercise for Parkinson's disease (PD), the role of aerobic exercise in the management of PD remained controversial. Objective: The purpose of this systematic review is to evaluate the evidence about whether aerobic exercise is effective for PD. Methods: Seven electronic databases, up to December 2013, were searched to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. Standardised mean difference (SMD) and 95% confidence intervals (CI) of random-effects model were calculated. And heterogeneity was assessed based on the I2 statistic. Results: 18 randomized controlled trials (RCTs) with 901 patients were eligible. The aggregated results suggested that aerobic exercise should show superior effects in improving motor actions (SMD, 20.57; 95% CI 20.94 to 2 0.19; p = 0.003), balance (SMD, 2.02; 95% CI 0.45 to 3.59; p = 0.01), and gait (SMD, 0.33; 95% CI 0.17 to 0.49; p <0.0001) in patients with PD, but not in quality of life (SMD, 0.11; 95% CI 20.23 to 0.46; p = 0.52). And there was no valid evidence on follow-up effects of aerobic exercise for PD. Conclusion: Aerobic exercise showed immediate beneficial effects in improving motor action, balance, and gait in patients with PD. However, given no evidence on follow-up effects, large-scale RCTs with long follow-up are warrant to confirm the current findings. © 2014 Shu et al.


PubMed | General Hospital of the Peoples Liberation Army Chengdu Military Region
Type: Journal Article | Journal: Journal of molecular neuroscience : MN | Year: 2014

Microgyria is associated with epilepsy and due to developmental disruption of neuronal migration. However, the role of endogenous subventricular zone-derived neural progenitors (SDNPs) in formation and hyperexcitability has not been fully elucidated. Here, we establish a neonatal cortex freeze-lesion (FL) model, which was considered as a model for focal microgyria, and simultaneously label SDNPs by CM-DiI. Morphological investigation showed that SDNPs migrated into FL and differentiated into neuronal and glia cell types, suggesting the involvement of endogenous SDNPs in the formation of FL-induced microgyria. Patch-clamp recordings in CM-DiI positive (CM-DiI(+)) pyramidal neurons within FL indicated an increase in frequency of spontaneous action potentials, while the resting membrane potential did not differ from the controls. We also found that spontaneous excitatory postsynaptic currents (EPSCs) increased in frequency but not in amplitude compared with controls. The evoked EPSCs showed a significant increase of 10-90% in rise time and decay time in the CM-DiI(+) neurons. Moreover, paired-pulse facilitation was dramatically larger in CM-DiI(+) pyramidal neurons. Western blotting data showed that AMPA and NMDA receptors were increased to some extent in the FL cortex compared with controls, and the NMDA/AMPA ratio of eEPSCs at CM-DiI(+) pyramidal neurons was significantly increased. Taken together, our findings provide novel evidence for the contribution of endogenous SDNPs in the formation and epileptogenicity of FL-induced focal microgyria.


PubMed | General Hospital of the Peoples Liberation Army Chengdu Military Region, Chongqing Medical University and General Hospital of Lanzhou
Type: | Journal: Oncotarget | Year: 2016

Focal cortical dysplasia (FCD) is a major cause of intractable epilepsy in children however the mechanisms underlying the pathogenesis of FCD and FCD induced epilepsy remain unclear. Increasing evidence suggests that the large-pore ion channels, pannexin 1 (Panx1) and 2 (Panx2), are involved in epilepsy and brain development. In this study, we investigated the expression of Panx1 and Panx2 in surgical samples from patients with FCD type Ia (FCDIa), type IIa (FCDIIa), and type IIb (FCDIIb) and in age-matched autopsy control samples. We found Panx1 mRNA and protein levels were both increased in all these FCD samples. Immunohistochemical analyses revealed that Panx1 was mainly distributed in microcolumn neurons, dysmorphic neurons (DNs), balloon cells (BCs) and reactive astrocytes. Double-labeled staining showed that the Panx1-positive neurons were mostly glutamatergic DNs and occasionally GABAergic normal-appearing neurons. Importantly, the protein levels of Panx1 positively correlated with the frequency of seizures. Intriguingly, the Panx2 mRNA and protein levels were only upregulated in FCDIIb lesions and characteristically expressed on SOX2-positive multipotential BCs. Immunofluorescent experiments identified that Panx2-positive BCs mainly expressed the neuronal differentiation transcription factor MASH1 but not the immature glial marker vimentin. Taken together, our results established a potential role of the specific expression and cellular distribution patterns of Panx1 and Panx2 in FCD-associated epileptogenesis and pathogenesis.


PubMed | General Hospital of the Peoples Liberation Army Chengdu Military Region
Type: Journal Article | Journal: PloS one | Year: 2014

Although some trials assessed the effectiveness of aerobic exercise for Parkinsons disease (PD), the role of aerobic exercise in the management of PD remained controversial.The purpose of this systematic review is to evaluate the evidence about whether aerobic exercise is effective for PD.Seven electronic databases, up to December 2013, were searched to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. Standardised mean difference (SMD) and 95% confidence intervals (CI) of random-effects model were calculated. And heterogeneity was assessed based on the I2 statistic.18 randomized controlled trials (RCTs) with 901 patients were eligible. The aggregated results suggested that aerobic exercise should show superior effects in improving motor actions (SMD, -0.57; 95% CI -0.94 to -0.19; p=0.003), balance (SMD, 2.02; 95% CI 0.45 to 3.59; p=0.01), and gait (SMD, 0.33; 95% CI 0.17 to 0.49; p<0.0001) in patients with PD, but not in quality of life (SMD, 0.11; 95% CI -0.23 to 0.46; p=0.52). And there was no valid evidence on follow-up effects of aerobic exercise for PD.Aerobic exercise showed immediate beneficial effects in improving motor action, balance, and gait in patients with PD. However, given no evidence on follow-up effects, large-scale RCTs with long follow-up are warrant to confirm the current findings.


PubMed | General Hospital of the Peoples Liberation Army Chengdu Military Region and Chongqing Medical University
Type: Journal Article | Journal: Experimental neurology | Year: 2016

Temporal lobe epilepsy (TLE) is a frequent form of focal intractable epilepsy in adults, but the specific mechanism underlying the epileptogenesis of TLE is still unknown. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) (the murine homolog gene called paired immunoglobulin-like receptor B, or PirB), participates in the process of synaptic plasticity and neurite growth in the central nervous system (CNS), suggesting a potential role of LILRB2 in epilepsy. However, the expression pattern of LILRB2 and the downstream molecular signal in intractable TLE remains poorly understood. In the present study, western blotting and immunohistochemistry results showed that LILRB2 expression was upregulated in the temporal neocortex of patients with TLE. Moreover, protein levels of LILRB2 negatively correlated with the frequency of seizures in TLE patients. In the pilocarpine-induced C57BL/6 mouse model, PirB upregulation in the hippocampus began 12h after status epilepticus (SE), reached a peak at 7days and then maintained a significantly high level until day 60. Similarly, we found a remarkable increase in PirB expression at 1day, 7days and30days post-SE in the temporal cortex. Double-labeled immunofluorescence showed that LILRB2/PirB were highly expressed in neurons and astrocytes but not microglia. In addition, protein levels of POSH, SHROOM3, ROCK1 and ROCK2, the important downstream factors of the LILRB2 pathway, were significantly increased in the epileptic foci of TLE patients and located on the NeuN-positive neurons and GFAP-positive astrocytes. Taken together, our results indicate that LILRB2/PirB may be involved in the process of TLE.


PubMed | Chengdu University of Traditional Chinese Medicine, General Hospital of the Peoples Liberation Army Chengdu Military Region and Chongqing Medical University
Type: Journal Article | Journal: Biochemical and biophysical research communications | Year: 2016

Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5-75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels. Furthermore, the migration of neural precursor cells (NPCs) derived from the subventricular zone (SVZ) toward the sits of injury was perturbed by treatment of NgR antagonist peptide NEP1-40. Invitro analysis showed that the knockdown of NgR by lentivirus-delivered siRNA promoted in axonal regeneration and SVZ-derived neural stem cell/progenitor cell (SVZ-NPCs) adhesion and migration, findings which were similar to the effects of NEP1-40. Taken together, our results indicate an important role for NgR in regulating the physiological processes of SVZ-NPCs. The observation of upregulated Nogo-A/NgR in lesion sites in the NFL model suggest that the effects of the perturbed Nogo-A are a key feature during the development and/or the progression of cortical malformation.

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