Scremin O U, Li M G, Jenden D J
Research Department, West Los Angeles VA Medical Center, UCLA School of Medicine, California 90073, USA.
J Neurotrauma. 1997 Aug;14(8):573-86. doi: 10.1089/neu.1997.14.573.
These experiments tested the role of cholinergic mechanisms in the changes of cerebral cortical blood flow (CBF) induced by brain trauma. CBF was measured with Iodo-14C-antipyrine autoradiography, in 128 cerebral cortex regions of both hemispheres, distributed in eight coronal slices. The effects of a 6.3-mm diameter craniotomy over the left motor-sensory cortex with no weight drop, and of trauma (drop weight of 20 g from 30 cm height on left motor-sensory cortex through a 6.3 mm circular craniotomy) on CBF were studied at 2 and 24 h after the interventions. A group of control animals that received no intervention was also set up. Animals were treated with the cholinesterase inhibitor physostigmine salicylate (3.3 microg/kg/min i.v. infusion started 60 min before CBF measurements), the cholinergic blocker scopolamine hydrobromide (1 mg/kg i.v. pulse, 18 min before CBF measurements), or with the drugs vehicle (saline). A focus of decreased CBF at the site of impact was observed 2 h after trauma, extending caudally as far as the occipital cortex. CBF on the contralateral cerebral cortex was also decreased. Both phenomena reversed partially at 24 h. This spontaneous recovery of CBF was blocked by scopolamine. Physostigmine reversed the decrease in CBF of the traumatized cortex, partially around the contused area and completely in more distant regions. The cerebral cortex contralateral to the trauma showed significantly higher CBF 24 h after trauma when compared to intact controls or craniotomy that peaked at the area symmetrical to the center of trauma. This phenomenon was also enhanced by physostigmine and completely blocked by scopolamine. These results suggest a prominent role of cholinergic mechanisms in the vascular adjustments that accompany cerebral trauma.
这些实验测试了胆碱能机制在脑外伤诱导的大脑皮质血流(CBF)变化中的作用。采用碘-14C-安替比林放射自显影术测量CBF,测量部位为双侧大脑半球的128个脑皮质区域,分布于8个冠状切片中。研究了在左运动感觉皮质上进行直径6.3毫米的开颅手术(无重物坠落)以及创伤(通过直径6.3毫米的圆形开颅手术,将20克重物从30厘米高度坠落在左运动感觉皮质上)对干预后2小时和24小时时CBF的影响。还设立了一组未接受干预的对照动物。给动物注射胆碱酯酶抑制剂水杨酸毒扁豆碱(在测量CBF前60分钟开始静脉输注,速率为3.3微克/千克/分钟)、胆碱能阻滞剂氢溴酸东莨菪碱(在测量CBF前18分钟静脉注射1毫克/千克)或药物载体(生理盐水)。创伤后2小时在撞击部位观察到CBF降低的区域,该区域向尾侧延伸至枕叶皮质。对侧大脑皮质的CBF也降低。这两种现象在24小时时部分逆转。东莨菪碱可阻断CBF的这种自发恢复。毒扁豆碱可逆转创伤皮质CBF的降低,在挫伤区域周围部分逆转,在更远区域完全逆转。与完整对照组或开颅手术组相比,创伤后24小时创伤对侧大脑皮质的CBF显著更高,在与创伤中心对称的区域达到峰值。毒扁豆碱可增强这一现象,而东莨菪碱可完全阻断这一现象。这些结果表明胆碱能机制在伴随脑外伤发生的血管调节中起重要作用。