Abstracts

Rationale: The current clinical treatments for temporal lobe epilepsy (TLE) are largely symptomatic and are usually accompanied with serious adverse effects. Recent study revealed that seizures may induce neurogenesis in rats. Therefore, in the present study, the possible neurogenesis in a model of kainic acid (KA)-induced seizures was investigated. Methods: Administration of KA, an analogue of the excitatory amino acid glutamate, can induce seizures in rats, leading to hippocampal lesions closely resembling human TLE. In the current study, we used KA to induce seizures in rats, and investigated the neurogenesis after KA treatment using BrdU incorperation. Results: We found that such treatment resulted in hippocampal lesions, especially in CA3 region, and also behavioral change mimicking those in human with TLE. Histopathological study showed that GFAP positive cells, representive for glial cells, were also increased in CA3 as well as CA1 areas at one week after KA injection. Additionally, KA-induced seizures were followed by the increase of BrdU-positive cells in both hippocampus and cerebral cortex, and the neurogenesis persisted for 3 days in both hippocampal CA1 and CA3 regions post KA administration. However, only very few BrdU-positive cells differentiated into GFAP-positive cells, indicating that only few proliferating cells were differentiated into glial cells. Passive avoidance test was used to evaluate the memory function of brain, and it revealed impaired memory in KA-treated rats. When growth factor was administered to the rats, the number of stem cells in hippocampal area was relatively increased and their behavior and memory was improved compared with those without growth factor treatment. Conclusions: In rats, KA-induced seizures are able to induce cell death in hippocampal region and behavioral change with subsequent neurogenesis. Growth factor therapeutical approach, which is able to induce proliferation and differentiation of neurons within hippocampus, is of great potential for future treatment in temporal lobe epilepsy.