Hypothermia suppresses the hippocampal neuroinflammation in the mouse model of global cerebral ischemia-reperfusion injury

We previously have found in mice that reducing the body temperature only during cerebral ischemia prevents the development of delayed neuronal death in the hippocampus after global cerebral ischemia (GCI). Inflammatory responses are profoundly involved in the development of neuronal death associated with cerebral ischemia, and the expression of inflammation-related genes and the accumulation and activation of glial cells are upregulated after cerebral ischemia-reperfusion, resulting in neuroinflammation. In this study, the effect of hypothermia (HT) during GCI on the expression of inflammation-related genes and the accumulation and activation of glial cells in the hippocampus after reperfusion was investigated. As a result, we found that increases in mRNA expression levels of TNF-alpha, IL-1 beta, CCL2, and COX-2 after GCI-reperfusion were suppressed by HT during GCI. Immunohistochemical evaluation also showed that HT during GCI suppressed the enhancement of the expression of the ionized calcium-binding adaptor protein 1 (Iba1), a microglial marker, by GCI in the hippocampus, whereas that of the glial fibrillary acidic protein (GFAP), an astrocytic marker, was unaffected by HT. Our findings suggest that HT during GCI suppresses the inflammatory responses after reperfusion in the hippocampus, particularly the accumulation of activated microglia, and elucidating the mechanism may lead to the development of novel neuroprotective drugs.