Abstract
The neurosteroid 17b-Estradiol (E2) has been reported to be against global ischemia-induced neuronal cell death by preventing apoptotic processes in the hippocampal CA1. It remains unknown, however, whether E2 treatment can also protect CA1 neurons from functional deficit caused by moderate ischemia. To address this issue, animals were subjected to a transient cerebral ischemia, which will lead to impairment in LTP induction, and the effect of E2 against this deficit was examined. Adult male Wistar rats were subjected to a transient four-vessel occlusion (4VO) by clamping the bilateral common carotid arteries. It was found that 10 min but 20 min clamping induced no observable cell death in CA1. We employed the 10 min ischemic animals and examined the electrophysological properties of their Shaffer collateral-CA1 synapses 7 days after the 4VO. Brains were cut into slices, stained with the voltage sensitive dye RH482 and subjected to real-time optical recordings. The ischemic brain showed a decreased synaptic transmission and an impairment of LTP induction but no alteration in paired-pulse facilitation (PPF), indicating that these dysfunctions occurred in postsynaptic neurons but not in presynaptic terminals. Administration of E2 (1-4 mg/kg) 3h before 4VO was found to be able to protect CA1 neurons from these ischemia-induced synaptic dysfunctions. Above results suggest that E2 can protect neurons not only from cell death but also from functional damages caused by cerebral ischemia. [Jpn J Physiol 55 Suppl:S154 (2005)]
