NEUROCHEMICAL MECHANISMS OF EXPERIMENTAL CONCUSSION

我们的目标是开发一种药物治疗方案， 头部受伤。 具体地说，我们将研究胆碱能神经的作用， 液体后神经功能缺损中特定脑区的神经元 大鼠撞击伤。 据推测， 脑内某些区域的胆碱能活动 损伤可能导致急性和更长时间的神经功能缺损。 的 急性和持久的神经功能缺损的机制可能非常 不同;一些更慢性的赤字可能反映减少 胆碱能活动在一些大脑区域在稍后的时间。 变化 胆碱能神经化学将与所选的神经学 在头部受伤后的不同时间出现缺陷。 根据以往的经验， 东莨菪碱预处理可减少神经功能缺损 在头部受伤后，东莨菪碱的作用将在 在受伤后的几天里。 将进行实验， 确定是否有一个限制的时间段，其中东莨菪碱必须 以减少持续的神经功能缺损。 具体 操纵中枢胆碱能神经元将被用来确认 东莨菪碱对神经功能影响的作用机制 中央 脑内注射可增强或减弱胆碱能神经张力 二异丙基氟磷酸盐（DFP）或半钬-3。 急性 神经学测试将包括测量简单反射（耳廓、角膜 和惊吓反射）以及姿势和伤害性躯体运动功能 （翻正和逃避反应，肌肉张力，运动活动，和爪 和尾部屈曲反射）。 将评估慢性神经功能缺损 通过测量在横梁上保持平衡的能力和学习回避任务， 需要协调的运动（梁行走）。 中枢胆碱能 活性将通过定量组织中的乙酰胆碱周转来评估 通过质谱碎片技术对特定大脑区域进行打孔， 测量来自输注的氘标记的相对掺入 磷酸胆碱前体转化为胆碱和乙酰胆碱。 乙酰胆碱 将在以下区域测量周转：背内侧脑桥 被盖/臂旁乳头核 和下丘脑后核，室管膜间核， 杏仁核、丘脑前腹侧核、海马、体 纹状体、前额叶皮质和顶叶皮质。

Our goal is to develop a pharmacological treatment regimen for conclusive head injury. Specifically, we will investigate the role of cholinergic neurons in specific brain areas in neurological deficits following fluid percussion injury in the rat. It is postulated that increases in cholinergic activity in certain brain areas immediately following head injury may lead to acute and longer lasting neurologic deficits. The mechanisms of acute and longer lasting neurological deficits may be very different; some of the more chronic deficits may reflect decreased cholinergic activity in some brain regions at the later times. Changes in cholinergic neurochemistry will be correlated with selected neurological deficits at various times following head injury. As previous experience has shown that scopolamine pretreatment reduces the neurological deficits following head injury, the actions of scopolamine will be measured at selected times following injury. Experiments will be performed to determine if there is a restricted time period in which scopolamine must be administered to reduce persistent neurological deficits. Specific manipulations of central cholinergic neurons will be used to confirm the mechanism of action of scopolamine on neurological outcome. Central cholinergic tone will be enhanced or decreased by intracerebral injection of diisopropylfluorophosphate (DFP) or hemicholium-3, respectively. Acute neurological testing will include measuring simple reflexes (pinna, corneal and startle reflexes) and postural and nociceptive somatomotor function (righting and escape responses, muscle tone, locomotor activity, and paw and tail flexion reflexes). Chronic neurological deficits will be assessed by measuring ability to to balance on a beam and a learned avoidance task requiring coordinated movement (beam-walking). Central cholinergic activity will be assessed by quantitating acetylcholine turnover in tissue punches of specific brain regions by a mass fragmentographic technique that measures the relative incorporation of deuterium label from infused phosphorylcholine precursor into choline and acetylcholine. Acetylcholine turnover will be measured in the following areas: dorsomedial pontine tegmentum, laterodorsal pontine tegmentum/parabrachial nucleus, mammillary and posterior nuclei of the hypothalamus, interpenducular nucleus, amygdala, anteroventral nucleus of the thalamus, hippocampus, corpus striatum, prefrontal cortex and parietal cortex.