Roland P E, Friberg L
Department of Clinical Physiology and Neurology, Bispebjerg Hospital, Copenhagen, Denmark.
J Cereb Blood Flow Metab. 1988 Jun;8(3):314-23. doi: 10.1038/jcbfm.1988.66.
We studied the effect of a gamma-aminobutyric acid (GABA)-A receptor-induced postsynaptic inhibition on regional CBF (rCBF) in awake humans. For this purpose we used a new specific GABA-A agonist, 4,5,6,7-tetrahydroisoxazolo(5,4)-pyridin-3-ol (THIP). As part of a new diagnostic procedure for the determination of which hemisphere subserved language, THIP was infused into the internal carotid artery 20 s before measurement of the rCBF. Administered by this route the THIP is distributed to the neocortex and neostriatum. THIP induced a dosage-dependent decrease of the rCBF. The rCBF decrease was not due to any direct effect on the cerebral vessels. The efficiency of the THIP-induced postsynaptic inhibition was tested by having the subjects voluntarily activate the inhibited cortex. During submaximal inhibition the subjects were able voluntarily to counteract decreases of rCBF in superior frontal cortex and motor cortex. Larger doses of THIP abolished this response and depressed the rCBF to baseline levels (20 ml/100 g/min). This was associated with 10-min total depression of function of the anterior two-thirds of the injected hemisphere. An analysis of the changes of rCBF in activated and nonactivated cortex--with and without THIP-induced inhibition--showed that it would be very unlikely that average increases in synaptic inhibition would increase rCBF in neocortical areas. Intracarotid injection of the water-soluble, nonirritative THIP is a very useful alternative to sodium amytal injection for determination of hemispheric dominance.
我们研究了γ-氨基丁酸（GABA）-A受体诱导的突触后抑制对清醒人类局部脑血流量（rCBF）的影响。为此，我们使用了一种新的特异性GABA-A激动剂，4,5,6,7-四氢异恶唑并[5,4]-吡啶-3-醇（THIP）。作为确定哪个半球负责语言功能的新诊断程序的一部分，在测量rCBF前20秒将THIP注入颈内动脉。通过这种途径给药，THIP分布到新皮质和新纹状体。THIP诱导rCBF剂量依赖性降低。rCBF降低并非由于对脑血管有任何直接影响。通过让受试者自愿激活受抑制的皮质来测试THIP诱导的突触后抑制的效果。在次最大抑制期间，受试者能够自愿抵消额上回皮质和运动皮质中rCBF的降低。更大剂量的THIP消除了这种反应，并将rCBF压低至基线水平（20毫升/100克/分钟）。这与注射半球前三分之二功能的10分钟完全抑制有关。对有THIP诱导抑制和无THIP诱导抑制情况下激活和未激活皮质中rCBF变化的分析表明，突触抑制平均增加极不可能增加新皮质区域的rCBF。颈内注射水溶性、无刺激性的THIP是用于确定半球优势的一种非常有用的替代硫喷妥钠注射的方法。
