Golding E M, Steenberg M L, Cherian L, Marrelli S P, Robertson C S, Bryan R M
Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurotrauma. 1998 Aug;15(8):635-44. doi: 10.1089/neu.1998.15.635.
The mechanisms associated with dysfunction of the cerebral vasculature following head trauma have not yet been fully elucidated. In an attempt to shed more light on the matter, we investigated the endothelial-mediated dilations in the rat middle cerebral artery (MCA) following severe traumatic brain injury (TBI). Rats were subjected to severe controlled cortical impact injury (CCI; 5 m/s, 130 ms duration, 3 mm deformation) over the right parietal cortex. At 24 h postinjury, ipsilateral segments of MCA and corresponding contralateral segments were isolated, mounted in a vessel chamber, and pressurized. The responses to 2 methylthio-ATP (2MeSATP), a selective agonist for the P2Y1 purinoceptors, N(omega)-nitro-L-arginine (L-NAME), an NO synthase inhibitor, and S-nitroso-N-acetylpenicillamine (SNAP), an exogenous NO donor, were determined. 2MeSATP elicited concentration dependent dilations in all MCAs studied. Ipsilateral MCAs harvested following TBI or sham-TBI, showed similar maximum dilations to 2MeSATP [70 +/- 4% (n = 17) and 72 +/- 6% (n = 13), respectively]. However, TBI reduced the concentration of 2MeSATP necessary to elicit one-half of the maximum dilation (EC50) from 15 to 9 nM (p < 0.05). Inhibition of NO synthase with 10(-5) M L-NAME abolished the dilation to 2MeSATP in both TBI and sham-TBI MCAs. The constriction to L-NAME was significantly reduced in TBI MCAs compared to sham vessels. Dilations to SNAP, an NO donor, were not altered by TBI indicating that the mechanisms of dilation involving NO in the vascular smooth muscle were not affected. Unlike other pathological conditions which often diminish endothelial-mediated responses, severe TBI enhanced the sensitivity to 2MeSATP without altering the maximum response.
头部创伤后脑血管功能障碍的相关机制尚未完全阐明。为了更深入地了解这一问题，我们研究了严重创伤性脑损伤（TBI）后大鼠大脑中动脉（MCA）的内皮介导舒张反应。对大鼠右侧顶叶皮层施加严重的可控皮质撞击伤（CCI；5 m/s，持续130 ms，3 mm变形）。伤后24小时，分离同侧MCA节段和相应的对侧节段，安装在血管腔室中并加压。测定对2-甲基硫代三磷酸腺苷（2MeSATP，P2Y1嘌呤受体的选择性激动剂）、N（ω）-硝基-L-精氨酸（L-NAME，一种一氧化氮合酶抑制剂）和S-亚硝基-N-乙酰青霉胺（SNAP，一种外源性一氧化氮供体）的反应。2MeSATP在所有研究的MCA中引起浓度依赖性舒张。TBI或假手术-TBI后收获的同侧MCA对2MeSATP的最大舒张反应相似[分别为70±4%（n = 17）和72±6%（n = 13）]。然而，TBI使引起最大舒张一半（EC50）所需的2MeSATP浓度从15 nM降至9 nM（p < 0.05）。用10^(-5) M L-NAME抑制一氧化氮合酶消除了TBI和假手术-TBI MCA中对2MeSATP的舒张反应。与假手术血管相比，TBI MCA中对L-NAME的收缩反应明显降低。对一氧化氮供体SNAP的舒张反应未因TBI而改变，表明血管平滑肌中涉及一氧化氮的舒张机制未受影响。与其他常常减弱内皮介导反应的病理状况不同，严重TBI增强了对2MeSATP的敏感性，而未改变最大反应。
