Mossy fiber sprouting in rats hippocampus of subclinical seizures following hypoxic brain injury

Abstract

Objective ：To investigate the abnormality of mossy fiber sprouting (MFS) and glial fibrillary acidic protein (GFAP) as well as neuronal loss in rats hippocampus during subclinical seizures following hypoxic cerebral insult. Methods ：Rats were assigned randomly into the control (n=12) and hypoxia group (n=91). Hypoxia was induced by treating the mice with 8% oxygen-nitrogen mixture gas, while control rats were treated with room air followed by the same procedures. According to the EEG records of epileptic discharges, hypoxia group rats were further divided into subclinical seizures group and non-subclinical seizures group. The changes in neuropathology, MFS in hippocampus and the expression of GFAP in cortex and hippocampus were examined by Nissl staining, Timm staining, immunohistochemistry staining and western-blot analysis, respectively. Results : 23.08% (21/91) rats exposed to hypoxia present subclinical seizures. Compared with non-subclinical seizures and control group, these mice showed significant neuronal loss of hippocampal CA1 and CA3 region as well as temporal cortex(P＜0.05) Also, as MFS scores in the hippocampal CA3 region increased (P<0.05), a higher expression of GFAP was detected, especially in hippocampal area (P＜0.05). However, the MFS score within inner molecular layer (IML) of the dentate gyrus (DG) was not significantly different among three groups mentioned above (P＞0.05). Conclusion ：In this study, we found the onset of subclinical seizures occurred following hypoxic brain injury in rats. Also, rats with epileptic discharges showed distinct neuronal loss, MFS in hippocampal CA3 subfield, and up-regulation of GFAP expression, which we proposed to be attributed to subclinical seizures following hypoxic cerebral damage.