Hypoxia inducible factor-1α expression is associated with hippocampal apoptosis during epileptogenesis

Cell apoptosis can cause hippocampal neuronal loss after epileptic seizures. Hypoxia inducible factor (HIF)-1 alpha is an important factor mediating apoptosis after brain injuries, such as cerebral ischemia and traumatic brain injures, but little research has been done on its role in the lithium chloride-pilocarpine induced epileptic model. Here, we used a rat model of pilocarpine-induced status epilepticus (SE) to investigate HIF-1 alpha expression and apoptosis in the hippocampus, and to explore their relationship during epileptogenesis. 120 male Sprague Dawley (SD) rats were treated with lithium chloride-pilocarpine injections and divided into an experimental group (administered by MK-801) and a positive control group (administered by saline). Then the HIF-1 alpha expression and hippocampal apoptosis were investigated by histological confirmation and western blotting at 24 h, 3 d, 7 d and 14 d, respectively. The results showed that the administration of MK-801 significantly reduced (P<0.05) HIF-1 alpha expression and hippocampal apoptosis during epileptogenesis in comparison with the positive control. Moreover, the expression of HIP-1 alpha and hippocampal apoptosis presented significant time-dependent changes (P<0.01) within 2 weeks, and their positive correlation (P<0.05) analyzed by Pearson's correlation analysis. Meanwhile, the HIF-1 alpha immunostained cells were distributed in accord with TUNEL immunostained cells and Caspase-3 immunopositive cells in the hippocampus. These results indicate that the HIP-1 alpha expression is associated with hippocampal apoptosis, and suggest that HIF-1 alpha is an important factor during epileptogenesis. (C) 2014 Elsevier B.V. All rights reserved.