臺灣博碩士論文加值系統

神經細胞興奮性的改變與腦血流量的變化間有著密切的關連。本實驗之主要目的乃在探討興奮性胺基酸 N-methyl-D-aspartate (NMDA) 引起腦血流量改變的現象，是否與神經細胞所釋出的一氧化氮有關。Sprague-Dawley大白鼠經 pentobarbital sodium (65mg/kg ip) 麻醉後，於其右側顱頂部進行顱窗開鑿以暴露局部大腦皮質表面；局部腦血流量之變化則以雷射杜卜勒血流計進行連續性之監測。顱窗內連續施加五分鐘之 NMDA (10-5 M 及 10-6 M)所引起的局部腦血流增加現象，具有 NMDA 的濃度梯度反應，而預先處理的 MK-801 (0.5mg/kg iv) 及 Tetrodotoxin (TTX; 10-6M; topicalapplication) 能抑制由 NMDA 所引起的腦血流的增加現象，但經由Acetylcholine (ACh, 10-7M 及 10-6M) 所引起的腦血流量增加現象，則不受 MK-801 及 TTX 的影響。給與具選擇性抑制神經細胞一氧化氮合成 酉每的 7-nitroindazole (7-NI; 50mg/kg ip)，則會顯著抑制由 NMDA 所引起的局部腦血流量增加現象，而 ACh 的反應，並不受 7-NI 的影響。另外，由 ACh 所引起的局部腦血流量增加現象，可經由局部施加的非選擇性一氧化氮合成酉每抑制劑 NG-nitro L-arginine (L-NNA, 10-4M) 所顯著抑制，但經由 nitroglycerin 所引起的腦血流量增加現象，並不受到影響。以上結果顯示，興奮性胺基酸 NMDA 所引起之局部腦血流增加現象與神經細胞興奮性之改變及一氧化氮合成的作用有關。

Neurons release nitric oxide (NO) in response to activation of recptors for the excitatory amino acid N-methyl-D-aspartate (NMDA) . The goal of the present study was to examine whether NO is involved in the response of cerebral blood flow (CBF) to NMDA. Anesthetized male Sprague-Dawley rats were equipped with a cranial window. Regional CBF of the parietal cortex was monitored by laser-Doppler flowmetry. Topical application of NMDA (10-6 M and 10-5 M) for 5 minutes produced dose-dependent increases in CBF. Responses of CBF to NMDA were inhibited after the pretreatment with MK-801 (0.5 mg/kg iv) or tetrodotoxin (10-6 M; topical application) . MK-801 or tetrodotoxin, however, had no effect on acetylcholine (ACh; 10-7 M and 10-6 M)-induced increases in CBF. The selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole (7-NI; 50 mg/kg ip) also significantly inhibited the increases in CBF produced by NMDA, but not by ACh. In addition, responses of CBF to ACh, but not nitroglycerin, were inhibited by the nonspecific inhibitor of nitric oxide synthase NG-nitro-L-arginine (L-NNA, 10-4 M; topical application) . These findings suggest that increases in CBF produced by NMDA is mediated by neuronally derived NO and dependent on neuronal activation.