Prevention of Hemorrhage and Death After Traumatic Blast Injury (TBI)

预防创伤性爆炸伤 (TBI) 后的出血和死亡

• 批准号: 8466813
• 负责人: RANDY H. KARDON
• 金额: --
• 依托单位: IOWA CITY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-10-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466813
• 关键词: Acute; Address; Affect; Afghanistan; Behavior; Blast Cell; Blast Injuries; Blindness; Blood Platelets; Blood Vessels; Brain; Brain hemorrhage; Caring; Cause of Death; Cessation of life; Chronic; Department of Defense; Development; Diffuse; Engineering; Experimental Models; Exposure to; Eye; Hemorrhage; Human; Injury; Iraq; Laboratories; Learning; Military Personnel; Modality; Molecular; Mus; Nervous System Trauma; Neurologic; Neurologic Dysfunctions; Neurons; Optic Nerve; Organ; Outcome; Patient Care; Patients; Pharmaceutical Preparations; Polymers; Prevention; Rehabilitation therapy; Reporting; Research; Retina; Shock; Site; Steroids; Structure; Symptoms; Testing; Traumatic Brain Injury; Treatment Efficacy; United States; United States Department of Veterans Affairs; Veterans; Vision; Visual; Visual Cortex; Visual system structure; abstracting; base; experience; improved; injured; mortality; novel; novel diagnostics; novel therapeutic intervention; prevent; research study

DESCRIPTION (provided by applicant): Abstract Traumatic brain injuries (TBI) and organ polytraumas caused by explosive blast have been identified as the most frequent cause of death and injury in current military engagements in Iraq and Afghanistan, with up to 20% of veterans returning to the United States having experienced some form of TBI. The explosive blast exposure in the battlefield conditions can cause peracute and acute symptoms of severe neurological dysfunction due to the blast induced shear damage to neurons and brain vasculature. Exposure to the blast wave can result in an immediate development of the shock and frequently results in the rapid death or chronic incapacitation, which dictates the need for more aggressive development of novel diagnostic and treatment modalities for TBI. We developed an experimental model of blast-induced TBI in mice and demonstrated that experimental mice exposed to blast wave share many features previously reported in human patients such are decreased visual function, abnormal vestibular function and impaired learning capacity. In this proposal we are planning to further expand on our studies and address following specific aims: we will thoroughly characterize effects of blast injury on the function and structure of brain and visual system (retina, optic nerve, visual cortex) by using battery of functional, structural, molecular and behavior based tests (Specific Aim I). Since we identified high correlation between brain hemorrhage and severe neurological damage and death, in this proposal we will evaluate the therapeutic efficacy of novel polymer-based synthetic platelet aggregators developed in our laboratory and evaluate whether this approach will decrease mortality and neurological and visual deficits associated with TBI (Specific Aim II). Furthermore, we managed to produce polymer-based synthetic platelets capable of targeted steroid release at sites of maximal vascular damage and we will investigate whether this novel therapeutic approach will decrease visual and neurological abnormalities in TBI injured brains and eyes (Specific Aim III). The successful outcome of this proposal may significantly improve our understanding of visual system and brain abnormalities associated with traumatic blast injury. Furthermore, development of synthetic polymer based platelets which can be engineered for targeted release of different drugs at the CNS sites with the most prominent vascular damage may be an effective strategy for preventing death and long term neurological problems associated with exposure to the blast injury. The proposed experiments in this study have a high relevance for the treatment and rehabilitation of wounded warriors and are consistent with current top priorities of the Veterans Administration and Department of Defense in terms of advanced care for patients affected by blast-induced traumatic brain injury.

描述（由申请人提供）： 摘要 爆炸爆炸引起的创伤性脑损伤 (TBI) 和器官多发伤已被确定为当前伊拉克和阿富汗军事行动中最常见的死伤原因，高达 20% 的返回美国退伍军人经历过一些创伤性脑损伤 (TBI) 和多器官损伤。 TBI 的形式。由于爆炸对神经元和脑血管系统造成剪切损伤，战场条件下的爆炸性爆炸可能导致严重神经功能障碍的超急性症状。暴露于爆炸波可能导致休克立即发生，并经常导致快速死亡或慢性失能，这表明需要更积极地开发新的 TBI 诊断和治疗方式。 我们开发了一种爆炸诱发的小鼠 TBI 实验模型，并证明暴露于爆炸波的实验小鼠具有许多先前在人类患者中报道过的特征，例如视觉功能下降、前庭功能异常和学习能力受损。在本提案中，我们计划进一步扩展我们的研究并解决以下具体目标：我们将通过使用一系列功能性神经元来彻底表征爆炸损伤对大脑和视觉系统（视网膜、视神经、视觉皮层）的功能和结构的影响。 、基于结构、分子和行为的测试（具体目标 I）。由于我们发现脑出血与严重神经损伤和死亡之间存在高度相关性，因此在本提案中，我们将评估我们实验室开发的新型聚合物合成血小板聚集剂的治疗效果，并评估这种方法是否会降低死亡率以及相关的神经和视觉缺陷与 TBI（特定目标 II）。此外，我们成功地生产出基于聚合物的合成血小板，能够在最大血管损伤部位靶向释放类固醇，我们将研究这种新的治疗方法是否会减少 TBI 损伤的大脑和眼睛的视觉和神经异常（具体目标 III）。 该提案的成功结果可能会显着提高我们对与创伤性爆炸损伤相关的视觉系统和大脑异常的理解。此外，开发基于合成聚合物的血小板可以在血管损伤最严重的中枢神经系统部位靶向释放不同的药物，这可能是预防死亡和与爆炸损伤相关的长期神经问题的有效策略。 本研究中提出的实验对于受伤战士的治疗和康复具有高度相关性，并且与退伍军人管理局和国防部目前在对爆炸引起的创伤性脑损伤患者进行高级护理方面的首要任务是一致的。