Graduate Program in Neuroscience, F.E. Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, USA.
Pharmacol Biochem Behav. 2013 Jul;108:66-73. doi: 10.1016/j.pbb.2013.04.001. Epub 2013 Apr 11.
Traumatic brain injury (TBI) is a worldwide phenomenon that affects all ages and socioeconomic classes and results in varying degrees of immediate and delayed motor, cognitive, and emotional deficiencies. A plethora of pharmacologic interventions that target recognized initiators and propagators of pathology are being investigated in an attempt to ameliorate secondary injury processes that follow primary injury. Diazoxide (DZ), a K(ATP) channel activator, has been shown to provide short- and long-term protective effects in a variety of in vitro and in vivo cerebral ischemia models. However, the effects of DZ on behavioral outcome following TBI have not been investigated. TBI was induced in male C57BL/6J mice by controlled cortical impact (CCI) and followed by intraperitoneal administration of either normal saline, dimethyl sulfoxide (DMSO), or 2.5 mg/kg DZ in DMSO, 30 min post-injury and daily for three days. Open field and beam walk performances were used to assess motor and behavioral function 1, 7, and 14 days following injury. Spatial learning and memory were assessed three weeks following injury using the Morris water maze. Injured mice were significantly impaired on the beam-walk and Morris water maze tasks, and were hyperactive and anxious in an open field environment. On post-injury days 1 and 14, mice treated with DMSO exhibited an increase in the amount of time required to perform the beam walk task. In addition, animals exposed to DMSO or DZ+DMSO exhibited slower swimming speed in the Morris water maze on the final day of testing. There was no therapeutic effect, however, of the treatment or vehicle on open field behavior or learning and memory function in the Morris water maze. In summary, CCI produced significant long-term impairment of motor, memory, and behavioral performance measures, and DZ administration, under the conditions used, provided no functional benefits following injury.
创伤性脑损伤（TBI）是一种全球性现象，影响所有年龄和社会经济阶层，导致不同程度的即时和延迟运动、认知和情感缺陷。大量针对病理公认启动子和传播子的药物干预措施正在被研究，试图改善原发性损伤后继发的损伤过程。二氮嗪（DZ），一种 KATP 通道激活剂，已被证明在各种体外和体内脑缺血模型中提供短期和长期的保护作用。然而，DZ 对 TBI 后行为结果的影响尚未被研究。雄性 C57BL/6J 小鼠通过皮质控制冲击（CCI）诱导 TBI，并在损伤后 30 分钟内通过腹腔内给予生理盐水、二甲亚砜（DMSO）或 2.5mg/kg DZ 在 DMSO 中，每天一次，持续三天。在损伤后 1、7 和 14 天，使用旷场和平衡木行走测试评估运动和行为功能。在损伤后 3 周，使用 Morris 水迷宫评估空间学习和记忆。损伤小鼠在平衡木行走和 Morris 水迷宫任务中明显受损，在旷场环境中表现出过度活跃和焦虑。在损伤后第 1 天和第 14 天，用 DMSO 治疗的小鼠在完成平衡木行走任务时所需的时间增加。此外，暴露于 DMSO 或 DZ+DMSO 的动物在测试的最后一天在 Morris 水迷宫中表现出较慢的游泳速度。然而，在旷场行为或 Morris 水迷宫中的学习和记忆功能方面，治疗或载体没有治疗效果。总之，CCI 导致运动、记忆和行为表现测量的长期显著损害，并且在使用的条件下，DZ 给药在损伤后没有提供功能益处。
