Effects of vitamin B3 on traumatic brain injury

维生素B3对脑外伤的影响

• 批准号: 7073208
• 负责人: MICHAEL R. HOANE
• 金额: $ 21.45万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7073208
• 关键词: apoptosis; behavior test; brain injury; chemotherapy; cognition disorders; disease /disorder model; drug screening /evaluation; edema; frontal lobe /cortex; gliosis; immunocytochemistry; laboratory rat; magnesium; nicotinamide; nonhuman therapy evaluation; pharmacokinetics; sensorimotor system; video microscopy; vitamins

DESCRIPTION (provided by applicant): Annually, approximately 2 million Americans suffer a moderate to severe traumatic brain injury (TBI). These injuries produce enduring disabilities that include cognitive, sensory, motor and emotional impairments. The associated health care costs from these injuries are staggering. One of the most at risk populations are the elderly, who can show twice the mortality of younger patients. Increasing age has also been shown to result in worse behavioral and pathological outcome. Confounding this major public health issue is the fact that currently there are very few pharmacological treatment options for patients who have suffered TBI. In addition, most preclinical therapeutics are never tested in older animals and many newly synthesized drugs fail in various stages of clinical testing. Given the fact that newly synthesized drugs fail in clinical trials it seems reasonable to begin to examine the potential efficacy of more natural substances. It has recently been demonstrated that administration of vitamin B3 (B3) following cortical contusion injury (CCI) resulted in a significant improvement in recovery of sensorimotor and cognitive function, as well as in a reduction of many of the secondary pathophysiological changes that occur following injury (i.e., neurodegeneration, edema formation and reactive gliosis). The proposed research will further investigate the preclinical efficacy of B3 utilizing an animal model of chronic and severe TBI-related behavioral impairments. We will use middle-aged (15 month old) rats in the CCI model to produce the severe deficits in order to test B3's ability to improve these deficits. The specific aims of this study are to: 1) determine if administration of B3 following injury can significantly reduce the sensorimotor and cognitive impairments seen following TBI in middle- aged rats; 2) determine if administration of B3 following injury in middle-aged rats can reduce injury-induced edema following TBI; 3) determine if administration of B3 following injury can reduce neuronal death, apoptosis and reactive gliosis following injury in middle-aged rats; and 4) determine if increased age has a deleterious effect on cerebral edema, neurodegeneration, apoptosis, and GFAP proliferation following TBI. The research proposed here will determine if B3 can overcome the severe behavioral and pathological outcomes associated with TBI in middle-aged subjects. This will be a critical step in determining the parameters for the development of B3 as a clinical treatment for TBI.

描述（由申请人提供）：每年，大约有200万美国人遭受中度至重度创伤性脑损伤（TBI）。这些伤害会造成永久性残疾，包括认知、感觉、运动和情感障碍。与这些伤害相关的医疗费用是惊人的。最危险的人群之一是老年人，他们的死亡率可能是年轻患者的两倍。年龄的增长也会导致更糟糕的行为和病理结果。混淆这一重大公共卫生问题的事实是，目前对创伤性脑损伤患者的药物治疗选择非常少。此外，大多数临床前疗法从未在老年动物身上进行过试验，许多新合成的药物在临床试验的各个阶段都失败了。鉴于新合成药物在临床试验中失败的事实，开始研究更多天然物质的潜在功效似乎是合理的。最近有研究表明，皮质挫伤（CCI）后给予维生素B3 （B3）可显著改善感觉运动和认知功能的恢复，并减少损伤后发生的许多继发性病理生理变化（即神经退行性变性、水肿形成和反应性神经胶质瘤）。该研究将利用慢性和严重tbi相关行为障碍的动物模型进一步研究B3的临床前疗效。我们将在CCI模型中使用中年（15个月大）大鼠产生严重的缺陷，以测试B3改善这些缺陷的能力。本研究的具体目的是：1)确定脑外伤后服用B3是否能显著减轻中年大鼠脑外伤后的感觉运动和认知障碍；2)确定中年大鼠损伤后给予B3是否能减轻TBI后损伤性水肿；3)观察损伤后给药B3是否能减少中年大鼠损伤后神经元死亡、细胞凋亡和反应性胶质细胞形成；4)确定年龄增加是否对脑外伤后脑水肿、神经退行性变、细胞凋亡和GFAP增殖有有害影响。这里提出的研究将确定B3是否可以克服中年受试者与TBI相关的严重行为和病理结果。这将是确定B3作为TBI临床治疗的参数的关键一步。