Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a...Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice （each a 20-minute occlusion of the middle cerebral artery） before inducing focal cerebral infarction （2 hour occlusion-reper- fusion in the same artery）. We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.展开更多
Some in vitro experiments have shown that erythropoietin （EPO） increases resistance to apoptosis and facilitates neuronal survival follow- ing cerebral ischemia. However, results from in vivo studies are rarely repo...Some in vitro experiments have shown that erythropoietin （EPO） increases resistance to apoptosis and facilitates neuronal survival follow- ing cerebral ischemia. However, results from in vivo studies are rarely reported. Perfusion-weighted imaging （PWI） and diffusion-weighted imaging （DWI） have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore, we hypothesized that PWI and DWI could be used to provide imaging evidence in vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion. To validate this hypothesis, we established a rat model of focal cerebral ischemia/ reperfusion injury, and treated with intra-cerebroventricular injection of EPO （5,000 U/kg） 20 minutes before injury. Brain tissue in the ischemic injury zone was sampled using MRI-guided localization. The relative area of abnormal tissue, changes in PWI and DWI in the ischemic injury zone, and the number of apoptotic cells based on TdT-mediated dUTP-biotin nick end-labeling （TUNEL） were assessed. Our findings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI, increases cerebral blood volume, and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion. The experiment pro- vides imaging evidence in vivo for EPO treating cerebral ischemia/reperfusion injury.展开更多
Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase （Mincle/Syk） signaling pat...Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase （Mincle/Syk） signaling pathway is a potential new target for treating cerebral hemorrhage. In this study, we aimed to determine whether acupuncture through Baihui （DU20） to Qubin （GBT） is an effective treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway. An intracerebral hemorrhage rat model was established by autol- ogous blood infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was performed for 30 minutes, once every 12 hours, for a total of three times. Piceatannol （34.62 mg/kg）, a Syk inhibitor, was intraperitoneally injected as a control. Modified neurological severity score was used to assess neurological function. Brain water content was measured. Immunohistochemistry and western blot assay were used to detect immunoreactivity and protein expression levels of Minde, Syk, and CARD9. Real-time polymerase chain reaction was used to determine interleukin-1[~ mRNA levels. Hematoxylin-eosin staining was performed to observe histopathological changes. Our re- suits showed that acupuncture through Baihui to Qubin remarkably improved neurological function and brain water content, and inhibited immunoreactivity and expression of Mincle, Syk, CARDg, and interkeukin-1β Moreover, this effect was similar to piceatannol. These find- ings suggest that acupuncture through Baihui to Qubin can improve neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk signaling pathway.展开更多
Decreased expression of brain-derived neurotrophic factor（BDNF） plays an important role in the pathogenesis of Alzheimer＇s disease, and a typical pathological change in Alzheimer＇s disease is neurofibrillary tangl...Decreased expression of brain-derived neurotrophic factor（BDNF） plays an important role in the pathogenesis of Alzheimer＇s disease, and a typical pathological change in Alzheimer＇s disease is neurofibrillary tangles caused by hyperphosphorylation of tau. An in vivo model of Alzheimer＇s disease was developed by injecting okadaic acid（2 μL） and exogenous BDNF（2 μL） into the hippocampi of adult male Wister rats. Spatial learning and memory abilities were assessed using the Morris water maze. The expression levels of protein phosphatase 2 A（PP2 A）, PP2 Ac-Yp307, p-tau（Thr231）, and p-tau（Ser396/404） were detected by western blot assay. The expression levels of BDNF, TrkB, and synaptophysin mRNA were measured by quantitative real-time polymerase chain reaction. Our results indicated that BDNF expression was suppressed in the hippocampus of OA-treated rats, which resulted in learning and memory deficits. Intra-hippocampal injection of BDNF attenuated this OA-induced cognitive impairment. Finally, our findings indicated an involvement of the PI3 K/GSK-3β/AKT pathway in the mechanism of BDNF in regulating cognitive function. These results indicate that BDNF has beneficial effect on Alzheimer＇s disease, and highlight the potential of BDNF as a drug target for treatment of Alzheimer＇s disease.展开更多
Previous studies have shown that transcranial pulse current stimulation(tPCS) can increase cerebral neural plasticity and improve patients' locomotor function.However, the precise mechanisms underlying this effect...Previous studies have shown that transcranial pulse current stimulation(tPCS) can increase cerebral neural plasticity and improve patients' locomotor function.However, the precise mechanisms underlying this effect remain unclear.In the present study, rat models of stroke established by occlusion of the right cerebral middle artery were subjected to tPCS, 20 minutes per day for 7 successive days.tPCS significantly reduced the Bederson score, increased the foot print area of the affected limbs, and reduced the standing time of affected limbs of rats with stroke compared with that before intervention.Immunofluorescence staining and western blot assay revealed that tPCS significantly increased the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra.This finding suggests that tPCS can improve the locomotor function of rats with stroke by regulating the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra.These findings may provide a new method for the clinical treatment of poststroke motor dysfunction and a theoretical basis for clinical application of tPCS.The study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine of China(approval No.PZSHUTCM190315003) on February 22, 2019.展开更多
The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusi...The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.展开更多
文摘Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice （each a 20-minute occlusion of the middle cerebral artery） before inducing focal cerebral infarction （2 hour occlusion-reper- fusion in the same artery）. We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.
文摘Some in vitro experiments have shown that erythropoietin （EPO） increases resistance to apoptosis and facilitates neuronal survival follow- ing cerebral ischemia. However, results from in vivo studies are rarely reported. Perfusion-weighted imaging （PWI） and diffusion-weighted imaging （DWI） have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore, we hypothesized that PWI and DWI could be used to provide imaging evidence in vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion. To validate this hypothesis, we established a rat model of focal cerebral ischemia/ reperfusion injury, and treated with intra-cerebroventricular injection of EPO （5,000 U/kg） 20 minutes before injury. Brain tissue in the ischemic injury zone was sampled using MRI-guided localization. The relative area of abnormal tissue, changes in PWI and DWI in the ischemic injury zone, and the number of apoptotic cells based on TdT-mediated dUTP-biotin nick end-labeling （TUNEL） were assessed. Our findings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI, increases cerebral blood volume, and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion. The experiment pro- vides imaging evidence in vivo for EPO treating cerebral ischemia/reperfusion injury.
基金supported by the National Natural Science Foundation of China,No.81473764,81273824the Key Project of Natural Science Foundation of Heilongjiang Province of China,No.ZD201204the Doctoral Fund Program of Ministry of Education of China,No.20102327110003
文摘Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase （Mincle/Syk） signaling pathway is a potential new target for treating cerebral hemorrhage. In this study, we aimed to determine whether acupuncture through Baihui （DU20） to Qubin （GBT） is an effective treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway. An intracerebral hemorrhage rat model was established by autol- ogous blood infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was performed for 30 minutes, once every 12 hours, for a total of three times. Piceatannol （34.62 mg/kg）, a Syk inhibitor, was intraperitoneally injected as a control. Modified neurological severity score was used to assess neurological function. Brain water content was measured. Immunohistochemistry and western blot assay were used to detect immunoreactivity and protein expression levels of Minde, Syk, and CARD9. Real-time polymerase chain reaction was used to determine interleukin-1[~ mRNA levels. Hematoxylin-eosin staining was performed to observe histopathological changes. Our re- suits showed that acupuncture through Baihui to Qubin remarkably improved neurological function and brain water content, and inhibited immunoreactivity and expression of Mincle, Syk, CARDg, and interkeukin-1β Moreover, this effect was similar to piceatannol. These find- ings suggest that acupuncture through Baihui to Qubin can improve neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk signaling pathway.
文摘Decreased expression of brain-derived neurotrophic factor（BDNF） plays an important role in the pathogenesis of Alzheimer＇s disease, and a typical pathological change in Alzheimer＇s disease is neurofibrillary tangles caused by hyperphosphorylation of tau. An in vivo model of Alzheimer＇s disease was developed by injecting okadaic acid（2 μL） and exogenous BDNF（2 μL） into the hippocampi of adult male Wister rats. Spatial learning and memory abilities were assessed using the Morris water maze. The expression levels of protein phosphatase 2 A（PP2 A）, PP2 Ac-Yp307, p-tau（Thr231）, and p-tau（Ser396/404） were detected by western blot assay. The expression levels of BDNF, TrkB, and synaptophysin mRNA were measured by quantitative real-time polymerase chain reaction. Our results indicated that BDNF expression was suppressed in the hippocampus of OA-treated rats, which resulted in learning and memory deficits. Intra-hippocampal injection of BDNF attenuated this OA-induced cognitive impairment. Finally, our findings indicated an involvement of the PI3 K/GSK-3β/AKT pathway in the mechanism of BDNF in regulating cognitive function. These results indicate that BDNF has beneficial effect on Alzheimer＇s disease, and highlight the potential of BDNF as a drug target for treatment of Alzheimer＇s disease.
基金supported by the National Key R&D Program of China, No.2018 YFC2001600(to CLS)the Shanghai Health Commission Accelerated the Development of Traditional Chinese Medicine Three-Year Action Plan Project, No.ZY(2018-2020)-CCCX-2001-06/2004-05(to CLS)+1 种基金the Program of Shanghai Academic Research Leader, No.19 XD1403600(to CLS)the National Natural Science Foundation of China for the Youth Project, No.81704163(to JJZ)。
文摘Previous studies have shown that transcranial pulse current stimulation(tPCS) can increase cerebral neural plasticity and improve patients' locomotor function.However, the precise mechanisms underlying this effect remain unclear.In the present study, rat models of stroke established by occlusion of the right cerebral middle artery were subjected to tPCS, 20 minutes per day for 7 successive days.tPCS significantly reduced the Bederson score, increased the foot print area of the affected limbs, and reduced the standing time of affected limbs of rats with stroke compared with that before intervention.Immunofluorescence staining and western blot assay revealed that tPCS significantly increased the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra.This finding suggests that tPCS can improve the locomotor function of rats with stroke by regulating the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra.These findings may provide a new method for the clinical treatment of poststroke motor dysfunction and a theoretical basis for clinical application of tPCS.The study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine of China(approval No.PZSHUTCM190315003) on February 22, 2019.
基金financially supported by grants from the National Natural Science Foundation of China,No.81371346,81271376Outstanding Postgraduate Fund of Xinxiang Medical UniversityScience and Technology Key Research Project of Henan Provincial Education Department of China,No.14A310019
文摘The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.
