Time-course pattern of neuronal loss and gliosis in gerbil hippocampi following mild, severe, or lethal transient global cerebral ischemia

Abstract

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 (Iba1) 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 dentate 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.

Experimental pretreatment with YES‑10®, a plant extract rich in scutellarin and chlorogenic acid, protects hippocampal neurons from ischemia/reperfusion injury via antioxidant role

“…Interestingly, it has been reported that scutellarin and/or chlorogenic acid display neuroprotective effects against brain ischemic insults in rodents ( 27 , 28 ). Therefore, the objective of this research was to analyze scutellarin and chlorogenic acid in YES-10 ® and examine the antioxidant efficacy of YES-10 ® in neuroprotection against ischemic injury induced by 5-min transient forebrain ischemia in gerbils, which have been used as a model of transient ischemia (TI) in the forebrain ( 19 , 29 ).…”

Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects

“…For instance, we have reported that ischemia-mediated neuronal loss/death in the caudate–putamen is different in the pattern of neuronal death according to the subregions of the caudate–putamen and ischemic duration (15 and 30 min) in a rat model of transient focal brain ischemia induced by middle cerebral artery occlusion (MCAO) [ 3 ]. In addition, it has been reported that a severer aspect of neuronal loss/death in the hippocampus is shown following 15 min of TFI than that in 5 min TFI in gerbils [ 2 ]. Furthermore, a rat model of focal brain ischemia induced by MCAO for over 1 h develops infarct lesion (necrotic tissue) which is easily visualized by 2, 3, 5-triphenyltetrazolium chloride (TTC) assay, but infarction does not occur in the brain induced by TFI for 5–15 min in gerbils when the TTC assay is applied, in which selective neuronal death only occurs [ 1 , 15 , 30 , 31 , 32 , 33 ].…”

“…As previously described [ 2 , 10 , 35 ], corresponding immunoreactive structures were analyzed in the CA1 region. Seven sections/gerbil were selected.…”

“…A brief period of ischemic condition in the brain causes ischemia-reperfusion injury, and it leads to selective neuronal loss/death in brain regions vulnerable to ischemia-reperfusion injury, such as the neocortex, hippocampus and striatum [ 1 , 2 , 3 , 4 ]. Transient forebrain ischemia (TFI) for 5 min causes death of pyramidal neurons in the hippocampal Cornu Ammonis 1 (CA1) region.…”

“…Transient forebrain ischemia (TFI) for 5 min causes death of pyramidal neurons in the hippocampal Cornu Ammonis 1 (CA1) region. The neuronal loss/death following 5 min TFI occurs from 4 or 5 days after TFI; thus, this phenomenon is termed as the “delayed neuronal death” [ 2 , 5 ].…”