Abstracts

Rationale: There is a growing interest to the mechanisms of seizure- induced neuronal injury in the human brain. Several studies report markers of neuronal death found in temporal lobes specimens removed surgically for intractable temporal lobe epilepsy (TLE). (Henshall et al., Neurology 2000; 55: 250-257; Yamamoto et al., J Neuropathol Exp Neurol 2006; 65: 217-225). The presence of the high nuclear expression of cyclin B (an enzyme specific for the G2 phase of the cell cycle) accompanied by neuronal cytoplasmic expression of the death-related Bax protein in the hippocampus of patients with epilepsy has been demonstrated (Nagy, Esiri, Exp Neurol 1998; 150:240-247) and interpreted as evidence of cell cycle disturbances associated with hippocampal neuronal cell death in TLE. However, further evidence of cell cycle disturbances is needed and the mechanisms still remain obscure. Methods: We evaluated neuronal expression of cell cycle proteins in 20 adult patients with chronic TLE undergoing temporal lobe surgery for seizure control. Surgically resected hippocampal specimens were fixed for pathomorphological/immunohistochemical analysis or frozen for biochemical analysis. Fixed samples were then stained for Nissl or cell cycle components. In frozen samples, cell cycle proteins were assayed using Western blots. Results: In hippocampal specimens we found neuronal expression of G2 cell cycle phase proteins (cyclin B1 and Cdc2), as well as PCNA. Western blots also revealed the expression of cell cycle proteins, including those of late phases. Most interesting, an appearance of binucleated neurons was revealed in many Nissl stained samples. Binucleated neurons looked degenerating or otherwise normal, some of them were PCNA-positive Conclusions: These results are the first evidence for neuronal binucleation in hippocampus of patients with chronic pharmacoresistant TLE and confirm the involvement of aberrant cell cycle in neuronal cell death in epilepsy.