Abstract:

Abstract:Objective
To investigate the effect of isoflurane on the synaptic long-term potentiation (LTP) in the CA1 area of the aged rat hippocampal slices，and elucidate the mechanisms of the effect of isoflurane on cognitive function in the aged rats. Methods Hippocampal slices (400  μm thick) were obtained from the brains of 70 male Sprague-Dawley rats that were decapitated. The slices were incubated in artificial cerebrospinal fluid (ACSF) at room temperature for at least 120 min before use. Thirty-five slices were randomly divided into 5 groups (n=7):control group,isoflurane groups(0.062 5,0.125 0,0.250 0 and 0.500 0 mmol/L). All the slices in each group were perfused with ACSF,isoflurane 0.062 5,0.125 0,0.250 0 or 0.500 0 mmol/L,respectively. The slices in each group were performed to record evoked population spikes (PS) using a extracellular microelectrode recording technique. Another thirty-five slices were randomly divided into 5 groups (n=7):LTP group,isoflurane-LTP groups (0.062 5,0.125 0,0.250 0 and 0.500 0 mmol?L-1). All the slices in each group were perfused with ACSF,isoflurane (0.062 5,0.125 0,0.250 0 and 0.500 0 mmol?L-1),respectively. PSs were recorded for at least 30 min before LTP in each group. For LTP induction,high-frequency stimulation (HFS) conditioning pulses (100 Hz/s) were applied to the Schaffer collateral-commissural pathway of hippocampus using a bipolar stimulating electrode. The changes in PS amplitude after HFS were analyzed in each group. Results  The PS amplitude of the rat hippocampal slices in isoflurane 0.062 5 mmol/Lgroup had no significant difference compared with control group(P>0.05). The PS amplitudes in isoflurane groups (0.125 0,0.250 0 and 0.500 0 mmol/L) were significantly decreased compared with control group (P<0.01). The PS amplitude in LTP group after HFS was significantly increased by (34±11)% compared with that of pre-HFS indicating the successful induction of LTP. Compared with LTP group,the amplitudes of the PS in isoflurane-LTP groups(0.062 5,0.125 0,0.250 0 and 0.500 0 mmol/L) after HFS were decreased significantly (P<0.01). Conclusion The inhibition of LTP induction in hippocampus of the aged rats may contribute to isoflurane-induced deficits in cognitive function of the aged rats.

Key words:  isoflurane;hippocampus;synapses;long-term potentiation;cognition disorders；aged