PATHOPHYSIOLOGY OF CHRONIC CEREBRAL VASOSPASMS
慢性脑血管痉挛的病理生理学
基本信息
- 批准号:3411518
- 负责人:
- 金额:$ 19.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1988
- 资助国家:美国
- 起止时间:1988-04-01 至 1994-08-31
- 项目状态:已结题
- 来源:
- 关键词:Macaca fascicularis calcium calcium channel cardiovascular disorder prevention catalase cerebral aneurysm cerebral artery cerebral hemorrhage cerebral ischemia /hypoxia cerebroangiography cytoskeleton disease /disorder model electron microscopy fluorescence microscopy fluorescent dye /probe free radical oxygen immunocytochemistry laboratory rabbit laboratory rat membrane lipids monoclonal antibody oxyhemoglobin pathologic process protein kinase C statistics /biometry urokinase vascular smooth muscle vasospasm voltage /patch clamp
项目摘要
About 30,000 North Americans have rupture of an intracranial aneurysm
each year. Because aneurysmal rupture, among all forms of intracranial
bleeding, almost uniquely deposits a large volume of blood clot on the
adventitial side of the basal conducting arteries, it is frequently the
cause of a delayed onset, long-lasting arterial constriction known as
vasospasm. Vasospasm can be so severe that the vessels may actually be
occluded and distal ischemia can result with attendant delayed infarction
- the second stroke. About two-thirds of ruptured aneurysm patients will
show moderate to severe degrees of angiographic vasospasm if subjected to
angiography a week or so after the initial hemorrhage. About half of
these patients will develop clinical signs of delayed ischemia. The
death rate from this phenomenon has fallen steadily in recent years with
the widespread avoidance of dehydration and antifibrinolytic agents. In
addition, calcium antagonists, hypertension and hypervolemia may have
exerted a beneficial effect. Currently, however, about 15% of patients
will still die or be severely damaged by vasospasm. Evidence of ischemic
cerebral infarction is noted in about 30% of the fatal cases of
aneurysmal ruptures if they survive past the initial few days.
Our long-term objectives are:
(1) prevention of vasospasm after subarachnoid hemorrhage;
(2) the successful treatment of established vasospasm.
The specific aims of the project are to determine:
(1) time course of cytoskeletal changes in arterial walls of cerebral
arteries after subarachnoid hemorrhage in monkeys; (2) pathogenesis and
prevention of oxyhemoglobin-induced cerebral vasospasm in monkeys; (3)
biochemical changes in arterial vessel wall as vasospasm develops and
abates; (4) time course of intracellular free calcium concentration
changes in cultured vascular smooth muscle cells following prolonged
exposure to oxyhemoglobin and if the mechanism of calcium entry is
sensitive to normal antagonists of calcium channels; (5) role of
activation of protein kinase C in production of cerebrovascular spasm;
(6) the source of increased intracellular calcium correlated with damage
by oxyhemoglobin; (7) if free radicals damage isolated cerebrovascular
smooth muscle cells primarily from the inside or outside; (8) whether
free radicals damage lipid components of surface membrane or ion
channels; (9) if transluminal balloon dilatation of spastic primate
cerebral arteries results in immediate and enduring improvement in vessel
caliber and whether there is any adverse structural change in the
arterial wall; (10) if intrathecal urokinase can prevent chronic cerebral
vasospasm in a primate model.
大约30,000名北美人患有颅内动脉瘤破裂
每年。因为在所有形式的颅内动脉瘤中,
出血,几乎是独一无二的,在血管上沉积了大量的血块
在基底传导动脉的外膜一侧,常为
延迟性、持续性动脉收缩的原因称为
血管痉挛。血管痉挛可能非常严重,以至于血管实际上可能
闭塞和远端缺血可导致延迟性脑梗塞
--第二杆。大约三分之二的破裂动脉瘤患者会
如果出现中度到重度的血管造影血管痉挛
血管造影术在最初出血后一周左右。大约一半的人
这些患者会出现延迟性缺血的临床症状。这个
近年来,这种现象的死亡率稳步下降,
广泛避免脱水和抗纤溶药物。在……里面
此外,钙拮抗剂、高血压和高容量血症可能有
起到了有益的作用。然而,目前约有15%的患者
仍然会因血管痉挛而死亡或严重受损。脑缺血的证据
脑梗塞在大约30%的死亡病例中被发现
如果动脉瘤在最初几天内存活下来,就会破裂。
我们的长远目标是:
(1)预防蛛网膜下腔出血后血管痉挛;
(2)已建立的血管痉挛的成功治疗。
该项目的具体目标是确定:
(1)脑动脉壁细胞骨架变化的时程
猕猴蛛网膜下腔出血后的动脉;(2)发病机制和
预防氧合血红蛋白诱发的猴脑血管痉挛;
血管痉挛发生和发展过程中动脉壁的生化变化
(4)细胞内游离钙浓度的时间进程
长时间培养的血管平滑肌细胞的变化
暴露于氧合血红蛋白以及钙进入的机制是否
对正常钙通道拮抗剂敏感;(5)
蛋白激酶C在脑血管痉挛发生中的激活;
(6)细胞内钙升高的来源与损伤有关。
通过氧合血红蛋白;(7)如果自由基损伤分离的脑血管
平滑肌细胞主要来自内或外;(8)
自由基破坏表面膜或离子的脂类成分
经络;(9)痉挛灵长类动物腔内气囊扩张
脑动脉导致血管即刻和持久的改善
是否有任何不利的结构性变化
动脉壁;(10)鞘内尿激酶是否能预防慢性脑血管疾病
灵长类动物模型中的血管痉挛。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
BRYCE K WEIR其他文献
BRYCE K WEIR的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('BRYCE K WEIR', 18)}}的其他基金
相似国自然基金
Calcium/NFAT/GLUT3通路调控糖酵解代谢在CAR-T细胞耗竭中的作用和机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
miR-30调控Calcium/Calcineurin通路在慢性肾脏病心肌保护中的作用
- 批准号:81670699
- 批准年份:2016
- 资助金额:58.0 万元
- 项目类别:面上项目
水稻OsCAS(Calcium-sensing Receptor)基因的功能分析
- 批准号:30900771
- 批准年份:2009
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
相似海外基金
L-type Calcium Channel SNP rs1006737: characterizing the genetic risks in MUD (Methamphetamine Use Disorder)
L 型钙通道 SNP rs1006737:表征 MUD(甲基苯丙胺使用障碍)的遗传风险
- 批准号:
10668210 - 财政年份:2023
- 资助金额:
$ 19.54万 - 项目类别:
Development of a Novel Calcium Channel Therapeutic for the Treatment of Asthma
开发治疗哮喘的新型钙通道疗法
- 批准号:
10603554 - 财政年份:2023
- 资助金额:
$ 19.54万 - 项目类别:
Development of a Novel Calcium Channel Therapeutic for Opioid Use Disorder
开发一种治疗阿片类药物使用障碍的新型钙通道疗法
- 批准号:
10684558 - 财政年份:2023
- 资助金额:
$ 19.54万 - 项目类别:
Development of a Novel Medication for Alcohol Use Disorder with an Active IND Dual Inhibitor of T-Type Calcium Channel and Soluble Epoxide Hydrolase
使用 T 型钙通道和可溶性环氧化物水解酶的活性 IND 双重抑制剂开发治疗酒精使用障碍的新型药物
- 批准号:
10815882 - 财政年份:2023
- 资助金额:
$ 19.54万 - 项目类别:
Novel Tools to Probe Trafficking and Function of Calcium Channel Signaling Complexes in Heart
探测心脏钙通道信号复合物的运输和功能的新工具
- 批准号:
10628914 - 财政年份:2023
- 资助金额:
$ 19.54万 - 项目类别:
Mechanisms of L-type Calcium Channel Regulation in Heart Health and Disease
L 型钙通道在心脏健康和疾病中的调节机制
- 批准号:
10734121 - 财政年份:2023
- 资助金额:
$ 19.54万 - 项目类别:
Structure-Function of Calcium Channel Complexes in Cardiac Physiology and Disease
钙通道复合物在心脏生理和疾病中的结构-功能
- 批准号:
10628911 - 财政年份:2023
- 资助金额:
$ 19.54万 - 项目类别:
Research Initiation Award: Defining the role of DJ-1 in regulating L-type voltage-dependent calcium channel expression in neuronal plasticity
研究启动奖:定义 DJ-1 在调节神经元可塑性中 L 型电压依赖性钙通道表达中的作用
- 批准号:
2200474 - 财政年份:2022
- 资助金额:
$ 19.54万 - 项目类别:
Standard Grant
Design and Preclinical Development of First-in-Class Selective T-type Calcium Channel Blockers for Chronic Pain
用于治疗慢性疼痛的一流选择性 T 型钙通道阻滞剂的设计和临床前开发
- 批准号:
452107 - 财政年份:2021
- 资助金额:
$ 19.54万 - 项目类别:
Operating Grants
Preventing the Calcium Channel Blocker – Lower Extremity Edema – Loop Diuretic Prescribing Cascade in Older Adults
预防钙通道阻滞剂 – 下肢水肿 – 老年人袢利尿剂处方级联
- 批准号:
10399417 - 财政年份:2021
- 资助金额:
$ 19.54万 - 项目类别: