Role of Vasopressin V1a and V2 Receptors for the Development of Secondary Brain Damage after Traumatic Brain Injury in Mice
Role of Vasopressin V1a and V2 Receptors for the Development of Secondary Brain Damage after Traumatic Brain Injury in Mice
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DOI：
10.1089/neu.2008.0597
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发表时间：
2008-12-01
影响因子：
4.2
通讯作者：
Plesnila, Nikolaus
中科院分区：
文献类型：
--
作者：
Trabold, Raimund;Krieg, Sandro;Plesnila, Nikolaus
脑水肿仍然是创伤性脑损伤（TBI）最有害的后遗症之一，其病理生理机制尚未充分了解。本研究的目的是探讨精氨酸加压素（AVP），也称为抗利尿激素（ADH），组织水稳态的重要调节剂，在脑外伤后脑水肿，颅内压（ICP），脑损伤和功能缺陷的形成中的作用。使C57/B16小鼠（n = 112）经受受控皮质撞击（CCI; 8 m/s，1 mm）。在创伤后3分钟，动物通过侧脑室注射500 ng AVP V-1 a受体拮抗剂（脱氨基-Pen（1），O-Me-Tyr（2），Arg（8）]-加压素）或500 ng AVP V-2受体拮抗剂（金刚烷乙酰基（1），O-Et-D-Tyr（2），瓦尔（4），Abu（6），Arg（8，9）]-加压素）。创伤后，评估脑含水量（24小时）、ICP（24小时）、挫伤体积（24小时和7天）和功能结果（1-7天）（每个实验组n = 8）。创伤后抑制AVP V-1a受体可使颅内压降低29%（p < 0.05），脑含水量降低45%（p < 0.05），继发性脑挫裂伤扩大降低37%（p < 0.05），并显著改善创伤后6、7天的运动功能（p < 0.05）。AVP V-2受体的抑制没有显著效果。目前的研究结果表明，加压素V-1a受体参与脑水肿形成的发病机制和继发性脑损伤后创伤性脑损伤的后续发展。因此，我们的研究表明，加压素V-1a受体可能是治疗创伤后脑水肿和继发性脑损伤的一个新的治疗靶点。
Brain edema is still one of the most deleterious sequels of traumatic brain injury (TBI), and its pathophysiology is not sufficiently understood. The goal of the Current study was to investigate the role of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), an important regulator of tissue water homeostasis, for the formation of post-traumatic brain edema, intracranial pressure (ICP), brain damage, and functional deficits following brain trauma. C57/B16 mice (n = 112) were subjected to controlled cortical impact (CCI; 8 m/s, 1 mm). At 3 min after trauma, animals received 500 ng of the AVP V-1a-receptor antogonist (deamino-Pen(1), O-Me-Tyr(2), Arg(8)]Vasopressin) or 500ng of the AVP V-2-receptor antagonist (adamantaneacetyl(1), O-Et-D-Tyr(2),Val(4), Abu(6),Arg(8,9)]-Vasopressin) by intracerebroventricular injection. After trauma, cerebral water content (24 h), ICP (24 h), contusion volume (24 h and 7 days), and functional outcome (1-7 days) were assessed (n = 8 per experimental group). Post-traumatic inhibition of AVP V-1a receptors reduced ICP by 29% (p < 0.05), brain water content by 45% (p < 0.05), and secondary contusion expansion by 37% (p < 0.05), and it significantly improved motor function 6 and 7 days after trauma (p < 0.05). Inhibition of AVP V-2 receptors had no significant effect. The current results demonstrate that vasopressin V-1a receptors are involved in the pathogenesis of brain edema formation and the subsequent development of secondary brain damage after traumatic brain injury. Accordingly, our Study suggests that vasopressin V-1a receptors may represent a novel therapeutic target for the treatment of post-traumatic brain edema and secondary brain damage.