权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

CENTRAL ADRENERGIC SYSTEM AND BLOOD BRAIN BARRIER

中枢肾上腺素能系统和血脑屏障

基本信息

批准号：
3407400
负责人：
SHELDON H PRESKORN
金额：
$ 10.15万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-01 至 1988-08-31
项目状态：
已结题

项目摘要

The principal investigator (P.I.), together with Dr. Boyd Hartman, discovered that tricyclic antidepressants increase blood: brain barrier permeability to diffusion-limited substances. In the previous grant, this effect was found to be dependent upon an intact central adregenergic system (CAS). Mianserin, a novel antidepressant which binds to both alpha-one and alpha-two adrenergic receptors, was also found to alter barrier permeability; whereas, antipsychotic drugs (dopamine receptor blockers) had no effect. Moreover, CO2 administration which increases the firing rate of the CAS was found to increase barrier permeability. This phenomenon was attenuated by pretreatment with the amine depletor, tetrabenazine (TBZ). To pursue this work, the P.I. and colleagues developed several small animal techniques to simultaneously measure barrier permeability and cerebral blood flow (CBF). In this grant, the P.I. will further examine neural modulation of barrier permeability and CBF and its relationship to cerebral energy utilization. Pursuing the anatomy underlying the CO2 effect and the mianserin and TBZ effect, the P.I. will assess the consequences of each of the following on CO2-induced changes in barrier permeability: (a) specific deletion of each biogenic amine system separately, (b) unilateral and bilateral lesions of the locus coeruleus, and (c) intracerebroventricular administration of selective adrenergic and serotonin receptor active drugs. We will determine the role of vasopressin in mediating CO2-induced changes in barrier permeability. To determine whether the ability to alter barrier permeability is a characteristic of antidepressant medications or is a more general pheomenon, we will assess effects of novel antidepressants and other drug classes. To further understand the biological import of these barrier changes, we will use ion-sensitive electrodes to examine concomitant changes in the extracellular space and will examine barrier changes to highly diffusion-limited substances. We will simultaneously use in vivo electrophysiological and electrochemical techniques together with barrier permeability and CBF measurements to study the CAS from cell body firing, neurotransmitter release, and end-organ response in the same animal to physiological stimuli.

主要研究者（PI），和博伊德·哈特曼博士一起发现三环类抗抑郁药增加血脑屏障对扩散受限物质的渗透性。在上一次拨款中，结果发现，这种作用依赖于一个完整的中枢肾上腺素能系统（CAS）。米安色林，一种新型抗抑郁药， α 2肾上腺素能受体，也被发现改变屏障渗透性;而抗精神病药物（多巴胺受体阻滞剂）没有效果。此外，增加燃烧率的CO2施用发现CAS增加了屏障渗透性。这种现象通过用胺消耗剂丁苯那嗪（TBZ）预处理来减弱。为了完成这项工作，PI。和同事们培育了几种小动物同时测量屏障渗透性和脑屏障通透性的技术血流量（CBF）。在这份补助金中，P.I.将进一步研究屏障的神经调节脑血流量与脑能量利用的关系。探索CO2效应、米安色林和TBZ的解剖学基础影响，P.I.将评估以下各项的后果 CO2诱导的屏障渗透性变化：（a）每种细胞的特异性缺失生物胺系统分别，（B）单侧和双侧病变蓝斑，和（c）脑室内施用选择性肾上腺素能和5-羟色胺受体活性药物。我们将确定加压素在介导CO2诱导的变化中的作用，屏障渗透性为了确定改变屏障的能力渗透性是抗抑郁药物的一个特征，一般现象，我们将评估新的抗抑郁药的影响，其他毒品种类为了进一步了解这些生物学意义，屏障的变化，我们将使用离子敏感电极来检查细胞外空间的伴随变化，并将检查屏障高度扩散限制物质的变化。我们将同时使用体内电生理学和电化学技术，屏障渗透性和CBF测量以研究来自细胞体的CAS 同一动物的放电、神经递质释放和终末器官反应对生理刺激的反应