Differences between Mild and Severe Ischemia-reperfusion Injury in Neuronal Death, Reactive Astrogliosis, and BBB Leakage in Gerbil Striata

Abstract

Background: Brain ischemia-reperfusion (IR) injury leads to reactive astrogliosis (the reaction of astrocytes) and the disruption of the blood-brain barrier (BBB) integrity, which are closely related to IR-induced neuronal damage or death (loss) in vulnerable brain regions. The aim of this study was to investigate and compare differences between mild and severe IR injury in neuronal death, reactive astrogliosis, and BBB leakage in the striatum using a gerbil model of transient forebrain ischemia. Methods: To examine mild and severe IR-induced neuronal death and reactive astrogliosis, seven gerbils at each time point in each group were allocated. The gerbils received 5-min (for mild IR) and 15-min (for severe IR) ischemia by bilateral common carotid artery occlusion. IR-induced modifications in motor behavior were examined through tests conducted for spontaneous motor activity and motor coordination. Histopathological changes in striatal cells were examined through histochemical staining. Additionally, immunohistochemistry and double immunofluorescence were performed to study reactive astrogliosis and BBB leakage following IR. Results: IR-induced neuronal death (loss) was observed in the striatum. Neuronal loss was more severe in gerbils with 15-min ischemia than in gerbils with 5-min ischemia. More abundant neurons died in the lateral field than in the medial field of the striatum. Reactive astrogliosis was more apparent in the lateral field than in the medial field, and the reaction was considerably more severe in the gerbils with 15-min ischemia than in those with 5-min ischemia. In particular, astrocyte endfeet around the blood vessels were more damaged (destroyed) and immunoglobulin G leakage in the parenchyma was more severe in the gerbils with severe IR than in those with mild IR. Conclusions: IR-induced neuronal death in the gerbil striatum was more apparent in the lateral field than in the medial field of gerbils with severe IR than in those with mild IR, which might be closely related to the degree of reactive astrogliosis and BBB disruption and dependent on ischemic duration and the vulnerable region.