Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of tr...Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1-3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Ibal) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1-3 region 2 days later and granule cell death in hippocampal de匚tate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5- minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No. KW-180124-1) on May 22, 2018.展开更多
Intracellular Ca2+ overload and the following Ca2+-toxicity are an important mechanism underlying ischemic brain injury.However,recent clinical trials using antagonists of the N-methyl-daspartate(NMDA) to prevent isch...Intracellular Ca2+ overload and the following Ca2+-toxicity are an important mechanism underlying ischemic brain injury.However,recent clinical trials using antagonists of the N-methyl-daspartate(NMDA) to prevent ischemic brain injury in humans have been largely disappointing.Activation of glutamate receptors resulting in intracellular Ca2+ overload and excitotoxicity couldn’t explain the whole process of ischemic brain injury,and emerging new studies have suggested that activation of several glutamate receptor-independent Ca2+-toxicity pathways also contribute to ischemic brain injury.This review focus on the roles of acid sensing ion channels(ASICs),Na+-Ca2+ exchanger(NCX) and transient receptor potential(TRP) channels in the ischemic brain injury.展开更多
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2016R1D1A1B01011790 to JHC)+3 种基金Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2017R1A2B4009079 to MHW)Cooperative Research Program for Agriculture Science and Technology Development(Project No.PJ01329401to MHW) Rural Development Administration,Republic of Korea
文摘Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1-3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Ibal) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1-3 region 2 days later and granule cell death in hippocampal de匚tate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5- minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No. KW-180124-1) on May 22, 2018.
文摘Intracellular Ca2+ overload and the following Ca2+-toxicity are an important mechanism underlying ischemic brain injury.However,recent clinical trials using antagonists of the N-methyl-daspartate(NMDA) to prevent ischemic brain injury in humans have been largely disappointing.Activation of glutamate receptors resulting in intracellular Ca2+ overload and excitotoxicity couldn’t explain the whole process of ischemic brain injury,and emerging new studies have suggested that activation of several glutamate receptor-independent Ca2+-toxicity pathways also contribute to ischemic brain injury.This review focus on the roles of acid sensing ion channels(ASICs),Na+-Ca2+ exchanger(NCX) and transient receptor potential(TRP) channels in the ischemic brain injury.
