Effects of mild hypothermia on the expression of glial fibrillary acidic protein and ultrastructural changes in astrocytes in the hippocampal CA1 subfield following global cerebral ischemia and reperfusion

Objective To observe the expression of glial fibrillary acidic protein ( GFAP), and the pathological and ultrastructnral changes of astrocytes in the CA1 subfield of the hippocampus following global cerebral ischemia and reperfusion, and to explore the neuroprotective mechanism of mild hypothermia. Methods Global cerebral ischemia was established in rats by a modified version of Pulsinelli's method. Ninety-six rats were divided into three groups including a sham-operated group, a normothermic ischemic reperfusion (IR) group and a hypothermic ischemic reperfusion (HIR) group. Each group had four subgroups which were sacrificed for 6, 12 or 24 hours, or 4 days after reperfusion (for each subgroup n = 8 ). Hematoxylin-eosin (HE) staining was used to observe morphological changes in neurons in the CA1 subfield of the hippocampus. TUNEL methods were used to detect apoptosis among those neurons. Immunohistochemical staining was used to detect the expression of GFAP in the CA1 subfield and the mechanism of astrocyte pathology. GFAP TUNEL double-labeled immunohistochemistry was used with both the shamoperated and experimental groups. Electron microscopy was also used to evaluate morphological changes in astrocytes 24 hours and 4 days after ischemia and reperfusion. Results Compared with the sham-operated group, expression of GFAP immunoreactive positive cells increased gradually in the CA1 subfield of the IR group rats. Compared with the IR group, expression of GFAP immunoreactive positive cells was significantly lower in the HIR group at all time points. Microscopic observation at the 4th day showed that some astrocytes in the CA1 subfield had died through oncosis. Conclusions Mild hypothermia can significantly decrease the expression of GFAP immunoreactive positive cells and the number of apoptotic neurons in the CA1 subfield of the hippocampus, minimize cell oedema and provide protection for neurons. Oncosis kills astrocytes following global cerebral ischemia and reperfusion. Key words: Global cerebral ischemia and reperfusion; Mild hypothermia;  Astrocytes; Glial fibrillary acidic protein; Oncosis