McIntosh T K, Hayes R L, DeWitt D S, Agura V, Faden A I
Department of Neurology, University of California, San Francisco.
Am J Physiol. 1987 Nov;253(5 Pt 1):E565-74. doi: 10.1152/ajpendo.1987.253.5.E565.
Although endogenous opioids have been implicated in the pathophysiology of spinal cord injury and brain ischemia, the role of specific opioid peptides and opiate receptors in the pathophysiology of traumatic brain injury remains unexplored. This study examined regional changes in brain opioid immunoreactivity and cerebral blood flow (CBF) after fluid-percussion brain injury in the cat and compared the effect of an opiate antagonist (Win 44,441-3 [Win-(-)]) with its dextroisomer Win 44,441-2 [Win-(+)] (which is inactive at opiate receptors) in the treatment of brain injury. Dynorphin A immunoreactivity (Dyn A-IR) but not leucine-enkephalin-like immunoreactivity accumulated in injury regions after traumatic injury; Dyn-IR increases also occurred predominantly in those areas showing significant decreases in regional CBF. Administration of Win-(-) but not Win-(+) or saline at 15 min after injury significantly improved mean arterial pressure, electroencephalographic amplitude, and regional CBF and reduced the severity and incidence of hemorrhage. Win-(-) also significantly improved survival after brain injury. Taken together, these findings suggest that dynorphin, through actions at opiate receptors, may contribute to the pathophysiology of secondary brain injury after head trauma and indicate that selective opiate-receptor antagonists may be useful in treatment of traumatic brain injury.
虽然内源性阿片类物质与脊髓损伤和脑缺血的病理生理学有关，但特定阿片肽和阿片受体在创伤性脑损伤病理生理学中的作用仍未得到探索。本研究检测了猫在流体冲击性脑损伤后脑阿片免疫反应性和脑血流量（CBF）的区域变化，并比较了阿片拮抗剂（Win 44,441-3 [Win-(-)]）与其右旋异构体Win 44,441-2 [Win-(+)]（在阿片受体上无活性）对脑损伤治疗的效果。创伤性损伤后，强啡肽A免疫反应性（Dyn A-IR）而非亮氨酸脑啡肽样免疫反应性在损伤区域积聚；Dyn-IR增加也主要发生在区域CBF显著降低的那些区域。损伤后15分钟给予Win-(-)而非Win-(+)或生理盐水可显著改善平均动脉压、脑电图振幅和区域CBF，并降低出血的严重程度和发生率。Win-(-)还显著提高了脑损伤后的生存率。综上所述，这些发现表明强啡肽通过作用于阿片受体，可能有助于头部创伤后继发性脑损伤的病理生理学过程，并表明选择性阿片受体拮抗剂可能对创伤性脑损伤的治疗有用。
