虚血性神経細胞死に対する迷走神経刺激の効果とその機序

Electrical stimulation of the vagus nerve (VNS) has shown efficacy in neuropathological conditions such as seizures and ischemia. However, its protective mechanism has been poorly examined to date. The present study was designed to clarify the mode of action of VNS in cerebral ischemia. Left VNS (0.4 mA, 40 Hz) was performed during 5-min ischemia in gerbils. The number of normal neurons in the bilateral CA1 subfield was counted 1 week after ischemia. In addition, extracellular glutamate and cerebral blood flow (CBF) in the dorsal hippocampus were measured using a dialysis electrode and a laser Doppler probe, respectively. Almost all neurons were killed by the 5-min ischemia in the Isch group. About 50% of the hippocampal neurons were rescued from ischemic insult by VNS, and this effect was prevented by transection of the vagus nerve centrally to the site of cervical stimulation. VNS significantly attenuated both ischemia-induced glutamate release and transient increase of hippocampal blood flow during reperfusion. Hyperemia as well as excessive glutamtate release after iscehmia is regarded as important factor in ischemic brain damage as it leads to generate considerble reactive oxygen spieces. Thus, VNS might protect neurons from ischemia-induced glutamate excitotoxicity and reperfusion injury via the afferent pathway of the vagus. [Jpn J Physiol 54 Suppl:S246 (2004)]