Local uncoupling of the cerebrovascular and metabolic responses to somatosensory stimulation after neuronal nitric oxide synthase inhibition
Local uncoupling of the cerebrovascular and metabolic responses to somatosensory stimulation after neuronal nitric oxide synthase inhibition
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DOI：
10.1097/00004647-199711000-00008
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发表时间：
1997-11-01
影响因子：
6.3
通讯作者：
Bonvento, G
中科院分区：
文献类型：
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作者：
Cholet, N;Seylaz, J;Bonvento, G
最近已经显示，使用基因工程突变小鼠（一氧化氮合酶[NOS]敲除）或特定的药理学工具，I型NOS（NOS的神经元同种型，[nNOS]）参与将脑血流与功能激活偶联。然而，尚未明确确定相关的代谢反应是否在nNOS抑制下保留，以及这种作用是否在脑内均匀发挥。为了解决这些问题，我们分析了在静息和功能激活期间抑制nNOS在α-氯醛糖麻醉的大鼠中的组合循环和代谢后果。在溶剂和7-硝基吲唑处理的大鼠中，在单侧胡须刺激诱导的三叉神经激活期间，使用[C-14]碘安替比林和[C-14]2-脱氧葡萄糖通过放射自显影测量脑血流量和脑葡萄糖使用（CGU）。我们的数据表明，抑制nNOS在不改变CGU的情况下降低了CBF，表明NO释放神经元在维持整个大脑的静息脑血管紧张度方面起着重要作用。在胡须刺激，nNOS抑制完全取消脑血管反应，只有在第二阶中继站（丘脑和体感皮层）的三叉神经中继不改变代谢反应。这些研究结果提供的证据表明，参与神经源性的NO在耦合流的体感激活是区域依赖性的，和nNOS抑制下，CBF和CGU可能会独立地在神经元激活过程中变化。
It has recently been shown, using either genetically engineered mutant mice (nitric oxide synthase [NOS] knockout) or specific pharmacological tools, that type I NOS (neuronal isoform of NOS, [nNOS]) participates in coupling cerebral blood flow to functional activation. However, it has not been clearly established whether the associated metabolic response was preserved under nNOS inhibition and whether this action was exerted homogeneously within the brain. To address these issues, we analyzed the combined circulatory and metabolic consequences of inhibiting the nNOS both at rest and during functional activation in the rat anesthetized with alpha-chloralose. Cerebral blood flow and cerebral glucose use (CGU) were measured autoradiographically using [C-14]iodoantipyrine and [C-14]2-deoxyglucose during trigeminal activation induced by unilateral whiskers stimulation in vehicle- and 7-nitroindazole-treated rats. Our data show that inhibition of nNOS globally decreased CBF without altering CGU, indicating that NO-releasing neurons play a significant role in maintaining a resting cerebrovascular tone in the whole brain. During whisker stimulation, nNOS inhibition totally abolished the cerebrovascular response only in the second order relay stations (thalamus and somatosensory cortex) of the trigeminal relay without altering the metabolic response. These findings provide evidence that the involvement of neurally-derived NO in coupling flow to somatosensory activation is region-dependent, and that under nNOS inhibition, CBF and CGU may vary independently during neuronal activation.