AZD0328 To Treat Traumatic Brain Injury

AZD0328 治疗创伤性脑损伤

• 批准号: 9917859
• 负责人: Charles S Cox
• 金额: $ 31.06万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-17 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9917859
• 关键词: Acetylcholine; Acute; Agonist; American; Antiinflammatory Effect; Attention; Blood - brain barrier anatomy; Brain; Brain Injuries; Brain Pathology; Cause of Death; Cells; Cerebral Edema; Chemicals; Clinical Research; Clinical Trials; Cognitive; Common Data Element; Communication; Data; Data Analyses; Dextrans; Diffusion Magnetic Resonance Imaging; Dose; Drug Kinetics; Elements; Extravasation; Female; Functional disorder; Funding; Hippocampus (Brain); Image; Immune; Immune system; Impaired cognition; Inflammation; Inflammatory; Informatics; Informed Consent; Injections; Injury; Interleukin-1 beta; Interleukin-6; Intervention; Intervention Studies; Ipsilateral; Label; Lead; Learning; Life; Logistics; Measures; Memory; Methods; Modeling; Neurotransmitters; Neutrophil Infiltration; Neutrophilic Infiltrate; Outcome; Outcome Measure; Parietal Lobe; Pathologic Processes; Pathway interactions; Patients; Performance; Peripheral; Pharmacologic Substance; Phase; Positron-Emission Tomography; Process; Protocols documentation; Public Health; Rattus; Receptor Activation; Regimen; Research; Rodent; Rodent Model; Role; Safety; Secondary to; Sex Differences; Signal Pathway; Spleen; Splenocyte; System; TNF gene; Testing; Therapeutic; Time; Tissues; Traumatic Brain Injury; United States; Vagus nerve structure; Vulnerable Populations; alpha-bungarotoxin receptor; axon injury; base; blood-brain barrier permeabilization; clinically relevant; cognitive function; cognitive testing; cytokine; data management; data sharing; disability; efficacy study; experience; experimental study; genotyped patients; improved; improved outcome; indexing; injured; injury-related death; macrophage; male; member; memory recognition; neuroinflammation; neuronal survival; nonhuman primate; novel; object recognition; patient population; preclinical study; primary outcome; programs; radioligand; regenerative; response; screening; survival outcome; treatment response; uptake; vagus nerve stimulation; water maze

Project Summary/Abstract Traumatic brain injury (TBI) is a leading cause of death and disability with approximately 1.7 million incidents occurring each year. There is an urgent need to develop new treatments that would limit brain pathology and improve overall outcome. Recently, a signaling pathway has been described that by which the brain regulates systemic inflammation. Specifically, this pathway acts on α7 nicotinic acetylcholine receptors (α7nAChR) present on peripheral immune cells to decrease inflammation. Activation of these receptors using chemical agonists decreases TBI-triggered inflammation, reduces blood-brain barrier permeability and improves cognitive outcome. The α7nAChR agonist AZD0328, developed by AstraZeneca, has been shown to improve cognitive function in normal rodents and non-human primates. However, it has not been tested if AZD0328 can reduce TBI-triggered inflammation, reduce brain pathology, or improve outcome. We propose to test the overall hypothesis that AZD0328 will reduce inflammation in rats following TBI (primary outcome). Further, it is anticipated that AZD0328 will reduce BBB permeability, brain pathology and improve cognitive outcome. If beneficial effects are observed, we will proceed to the planning of a Phase II efficacy study. We propose two aims to test our hypothesis: Aim 1 (UG3): To examine if AZD0328 reduces peripheral and central inflammation and improves outcome in traumatically brain injured rats. Aim 2 (UH3): Clinical Trial Planning.

项目总结/文摘