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| 1 | Neuronal tolerance to hypoxia-ischemia through recombinant adeno-associated viral vectors expressing neuronal and inducible nitric oxide synthase An in vivo study显示文摘BACKGROUND: Studies have confirmed that neuronal nitric oxide synthase (nNOS) mediates neurotoxic effects during the early stages of hypoxia-ischemia,while inducible nitric oxide synthase (iNOS) mediates delayed neurotoxicity during advanced stages of hypoxia-ischemia. OBJECTIVE: This study was designed to observe neuronal apoptosis and the expressions of nNOS,iNOS,p38 mitogen-activated protein kinase (MAPK),and caspase-3 mRNA following transfection of recombinant adeno-associated viral vectors separately expressing nNOS and iNOS antisense (rAAV-AsnNOS and rAVV-AsiNOS,respectively) into rat brains subjected to cerebral ischemia; to analyze mechanisms underlying elevated neuronal tolerance to hypoxia-ischemia. DESIGN: A randomized controlled in vivo experiment. SETTING: Fujian Institute of Neurosurgery & Department of Neurosurgery,Union Hospital,Fujian Medical University. MATERIALS: Eighty healthy adult male Sprague Dawley rats of clean grade were provided by the Zhejiang Laboratory Animal Center,China. The protocol was performed in accordance with ethical guidelines for the use and care of animals. The following vectors,rAAV-AsnNOS,rAAV-AsiNOS,and rAAV expressing the β-galactosidase gene (rAAV-LacZ),were successfully constructed by Fujian Institute of Neurosurgery. Rabbit anti-mouse nitrotyrosine (NT) monoclonal antibody (Zhongshan Jinqiao Biotechnology Co.,Ltd.,Beijing,China) and reverse transcription-polymerase chain reaction (RT-PCR) kit (two-step method) (Promega Company,USA) were used in this study. METHODS: This study was performed at the Fujian Institute of Neurosurgery in December 2003. Sixty rats were randomly divided into 3 groups,with 20 rats in each group: rAAV-AsnNOS group,rAAV-AsiNOS group,and rAAV-LacZ group. The remaining 20 rats served as controls. Pre-treated viral vectors (rAAV-AsnNOS,rAAV-AsiNOS,and rAAV-LacZ,respectively; each 50 μL,virus titer of 2×109 viral particles/mL) were transfected into the cerebral cortex of the targeted. Phosphate buffer saline (50 μL) was perfused identically into the rat cerebral cortex of the control group. All rats were subjected to cerebral ischemia by occluding the right middle cerebral artery with suture. Five time points (0,1,6,24,72 hours of ischemia,4 rats for each time point) were allotted to each group. Ischemic brain tissue specimens were prepared for index measurement. MAIN OUTCOME MEASURES: The percentage of NT-positive cells and apoptotic cells in the rat ischemic brain tissue specimens were measured by flow cytometry. The expressions of nNOS,iNOS,p38MAPK,and caspase-3 mRNA were measured by RT-PCR. RESULTS: During the early stages of ischemia (at 1 and 6 hours) with rAAV-AsnNOS transfection,the percentage of NT-positive cells,apoptotic cells,and the expressions of nNOS,p38MAPK and caspase-3 mRNA in the brain nerve cells were remarkably reduced compared to the control,rAAV-LacZ,and rAAV-AsiNOS groups. During the advanced stages of ischemia (at 24 and 72 hours) with rAAV-AsiNOS transfection,the above-mentioned indices were significantly reduced compared to control,rAAV-LacZ,and rAAV-AsnNOS groups. CONCLUSION: Following rAAV transfection,neuronal cells resisted ischemic injury in the MCAO ischemic rat model. Neurons transfected with rAAV-AsnNOS inhibited expression of nNOS,p38MAPK,and caspase-3 during the early stages of ischemia,and those transfected by rAAV-AsiNOS inhibited above-mentioned index expression during the advanced stages of ischemia. These results clearly demonstrate that neuronal apoptosis can be inhibited through the use of nNOS antisense. | Chunmei Chen Weizhong Yang Chunhua Wang Songsheng Shi Jianping Chen Yong Huang Dongsheng Cai | 2008 | Neural Regeneration Research2008，3，2： | 3 |
| 2 | Molecular diagnosis and treatment of meningiomas:an expert consensus(2022)显示文摘Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations.The fifth edition of the WHO Classification of Tumors of the Central Nervous System(WHO CNS5),published in 2021,introduces major changes that advance the role of molecular diagnostics in meningiomas.To follow the revision of WHO CNS5,this expert consensus statement was formed jointly by the Group of Neuro-Oncology,Society of Neurosurgery,Chinese Medical Association together with neuropathologists and evidence-based experts.The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. | Jiaojao Deng Lingyang Hua Liuguan Bian Hong Chen Ligang Chen Hongwei Cheng Changwu Dou Dangmurenjiapu Geng Tao Hong Hongming Ji Yugang Jiang Qing Lan Gang Li Zhixiong Liu Songtao Qi Yan Qu Songsheng Shi Xiaochuan Sun Hajun Wang Yongping You Hualin Yu Shuyuan Yue Jianming Zhang Xiaohua Zhang Shuo Wang Ying Mao Ping Zhong Ye Gong Group of Neuro-Oncology Society of Neurosurgery Chinese Medical Association | 2022 | Chinese Medical Journal2022，135，16： | 1 |
| 3 | Over-expression of nitric oxide and nitric oxide synthase in the rat brain following focal ischemia显示文摘BACKGROUND: In cerebral ischemia,over-expression of nitric oxide (NO) exerts neurotoxic effects. OBJECTIVE: This study was designed to measure NO and nitric oxide synthase (NOS) expression in rat brain tissue during cerebral ischemia,and to correlate expression levels of NO and NOS with ischemic time. DESIGN: A complete randomized grouping design,controlled animal experiment. SETTING: Fujian Institute of Neurosurgery & Department of Neurosurgery,Union Hospital Affiliated Fujian Medical University. MATERIALS: This study was performed at the Fujian Institute of Neurosurgery in December 2003. Eighty healthy adult male Sprague Dawley (SD) rats of clean grade were provided by the Zhejiang Laboratory Animal Center. The protocol was performed in accordance with ethical guidelines for the use and care of animals. Kits for measuring NO expression by method of nitrate reductase (Boster Company,Wuhan,China) and NOS activity (Jiancheng Bioengineering Co.,Ltd.,Nanjing,China),as well as a kit for reverse transcription-PCR (RT-PCR,Promega,USA) were used in the present study. METHODS: Sixty-eight rats underwent cerebral ischemia by occluding the middle cerebral artery by suture method. Forty-eight successfully lesioned rats were included in the study. Six rats were used for each length of ischemic event (30 minutes,1,3,6,12,24,and 72 hours,and 5 days of ischemia). Additionally,a normal control group (n = 6,normally raised) and a sham-operated group (n = 6,corresponding cerebral vessels exposed,without occlusion of middle cerebral artery) were included in the analysis. MAIN OUTCOME MEASURES: Neurological function deficits were scored according to methods of Longa,Bederson,and colleagues. NO levels and NOS activity in the brain tissue were measured via nitrate reductase and chemical colorimetry,respectively. The expression of nitrotyrosine (NT),an in vivo specific metabolite of NO,was quantitatively measured by flow cytometry. Expression of endothelial,neuronal,and inducible NOS mRNA (eNOS,nNOS,and iNOS mRNA,respectively) in the cerebral ischemic region were semi-quantitatively analyzed by RT-PCR. RESULTS: Forty-eight ischemic rats and six sham-operated rats were analyzed. Neurological functional deficits increased with ischemic times (r = 0.765,P < 0.05). There were no significant differences in NO levels,NOS activity,and the percentage of NT-positive cells between the sham-operated and the normal control groups (P > 0.05). NO levels,NOS activity,and the percentage of NT-positive cells in brain tissue positively correlated to ischemia times (r = 0.932,0.914,0.924,respectively,P < 0.05). The percentage of NT-positive cells began to noticeably increase within 0.5 hour of after ischemia (9.50 %). NOS activity began to increase within 0.5 hour of ischemia and reached its peak level 3 days after ischemia. RT-PCR semi-quantitative analysis demonstrated that in the early stages of ischemia (0.5-6 hours),the expression of both eNOS and nNOS mRNA increased with ischemic time (t = 28.482-100.459,P < 0.01),while iNOS mRNA levels were almost undetectable. In the middle and advanced stages of ischemia (6 hours-5 days),iNOS mRNA levels were significantly increased compared to the control group (t = 36.742-82.058,P < 0.01); however,eNOS and nNOS mRNA levels were markedly reduced. CONCLUSION: With the prolongation of ischemic time,NO levels increased in cerebral tissue due to activation of various NOS. These measurements correlated with an increase in NT-positive cells and behavioral deficits. In the early stages of ischemia,eNOS and nNOS activities were increased,while in the later stage of ischemia,iNOS activity was increased and eNOS and nNOS activities were reduced. | Weizhong Yang Chunmei Chen Chunhua Wang Songsheng Shi Junrong Lei Yongliang Zhang | 2008 | Neural Regeneration Research2008，3，2： | 1 |
| 4 | Ischemic preconditioning reduces ischemic brain injury by suppressing nuclear factor kappa B expression and neuronal apoptosis显示文摘Ischemic stroke induces a series of complex pathophysiological events including blood-brain barrier disruption, inflammatory response and neuronal apoptosis. Previous studies demonstrate that ischemic preconditioning attenuates ischemic brain damage via inhibiting blood-brain barrier disruption and the inflammatory response. Rats underwent transient (15 minutes) occlusion of the bilateral common carotid artery with 48 hours of reperfusion, and were subjected to permanent middle cerebral artery occlusion. This study explored whether ischemic preconditioning could reduce ischemic brain injury and relevant molecular mechanisms by inhibiting neuronal apoptosis. Results found that at 72 hours following cerebral ischemia, myeloperoxidase activity was enhanced, malondialdehyde levels increased, and neurological function was obviously damaged. Simultaneously, neuronal apoptosis increased, and nuclear factor-κB and cleaved caspase-3 expression was significantly increased in ischemic brain tissues. Ischemic preconditioning reduced the cerebral ischemia-induced inflammatory response, lipid peroxidation, and neurological function injury. In addition, ischemic preconditioning decreased nuclear factor-κB p65 and cleaved caspase-3 expression. These results suggested that ischemic preconditioning plays a protective effect against ischemic brain injury by suppressing the inflammatory response, reducing lipid peroxidation, and neuronal apoptosis via inhibition of nuclear factor-κB and cleaved caspase-3 expression. | Songsheng Shi Weizhong Yang Xiankun Tu Chunmei Chen Chunhua Wang | 2013 | Neural Regeneration Research2013，8，7： | 0 |
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