Alagarsamy S, DeWitt D S, Johnson K M
Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, USA.
J Neurotrauma. 1998 Aug;15(8):627-33. doi: 10.1089/neu.1998.15.627.
Experimental traumatic brain injury (TBI) damages cerebral vascular endothelium and reduces cerebral blood flow (CBF). The nitric oxide synthase (NOS) substrate, L-arginine, prevents CBF reductions after TBI, but the mechanism is not known. This study examined the possibility that post-traumatic hypoperfusion is due to reductions in the substrate sensitivity of NOS which are overcome by L-arginine. Isoflurane-anesthetized rats were prepared for TBI (midline fluid-percussion, 2.2 atm), sham-TBI, or no surgery (control), and were decapitated 30 min after injury or sham injury. The brains were removed and homogenized or minced for measurements of crude soluble or cell-dependent stimulated NOS activity, respectively. Baseline arterial oxygen, carbon dioxide, pH, or hemoglobin levels did not differ among control, sham, or TBI groups. Total cortical soluble NOS activity in TBI-treated rats was not significantly different from either untreated or sham groups when 0.45 microM or 1.5 microM L-arginine was added. Also, there were no differences in cell-dependent NOS activity among the three groups stimulated by 300 microM N-methyl-D-aspartate, 50 mM K+, or 10 microM ionomycin. These data suggest that TBI reduces CBF by a mechanism other than altering the substrate specificity or activation of nNOS.
实验性创伤性脑损伤（TBI）会损害脑血管内皮并减少脑血流量（CBF）。一氧化氮合酶（NOS）的底物L-精氨酸可防止TBI后CBF降低，但其机制尚不清楚。本研究探讨了创伤后灌注不足是否是由于NOS底物敏感性降低所致，而L-精氨酸可克服这种降低。将异氟烷麻醉的大鼠制备成TBI（中线液体冲击，2.2个大气压）、假TBI或不进行手术（对照）模型，并在损伤或假损伤后30分钟断头。取出大脑并分别进行匀浆或切碎处理，以测量粗可溶性或细胞依赖性刺激的NOS活性。对照、假手术或TBI组之间的基线动脉血氧、二氧化碳、pH或血红蛋白水平无差异。当添加0.45微摩尔或1.5微摩尔L-精氨酸时，TBI处理大鼠的总皮质可溶性NOS活性与未处理或假手术组相比无显著差异。此外，在由300微摩尔N-甲基-D-天冬氨酸、50毫摩尔钾离子或10微摩尔离子霉素刺激的三组中，细胞依赖性NOS活性也无差异。这些数据表明，TBI通过改变nNOS的底物特异性或激活以外的机制降低CBF。
