Determination of factors that influence addiction-related outcomes following brain injury

确定影响脑损伤后成瘾相关结果的因素

• 批准号: 10454784
• 负责人: BRIAN D STEMPER
• 金额: --
• 依托单位: CLEMENT J. ZABLOCKI VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10454784
• 关键词: Abstinence; Accident and Emergency department; Afghanistan; Air Force Personnel; American; Analgesics; Animals; Behavior; Behavioral; Blast Injuries; Brain; Brain Injuries; Brain region; Chemistry; Chronic; Clinical Treatment; Conflict (Psychology); Data; Department of Defense; Devices; Diffusion Magnetic Resonance Imaging; Disease; Dose; Drug Addiction; Drug abuse; Excision; Experimental Models; Exposure to; Freedom; Functional Magnetic Resonance Imaging; Gliosis; Healthcare Systems; Human; Image; Imaging Techniques; Immunohistochemistry; Incidence; Individual; Inflammatory Response; Injury; Intake; Intervention; Intravenous; Investigation; Iraq; Laboratories; Lead; Life; Link; Long-Term Effects; Magnetic Resonance Imaging; Measures; Medial; Military Personnel; Mission; Modeling; Nervous System Trauma; Neurologic; Non-Steroidal Anti-Inflammatory Agents; Opiate Addiction; Opioid; Outcome; Oxycodone; Pathologic; Patients; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacological Treatment; Pharmacotherapy; Phase III Clinical Trials; Play; Population; Predisposition; Prefrontal Cortex; Prevalence; Property; Psychological reinforcement; Public Health; Publishing; Rattus; Recording of previous events; Reinforcement Schedule; Relapse; Research; Risk; Rodent; Rodent Model; Role; Seeds; Self Administration; Structure; Substance abuse problem; Testing; Time; Traumatic Brain Injury; Veterans; abuse liability; addiction; addiction liability; brain tissue; combat; combat casualty; comorbidity; craving; drug efficacy; drug of abuse; drug relapse; drug seeking behavior; effectiveness study; epidemiology study; experience; frontal lobe; hazard; heroin use; high risk; improved; mild traumatic brain injury; military veteran; misuse of prescription only drugs; neuroimaging; operation; opioid exposure; opioid use; pre-clinical; preclinical study; prescription opioid; rehabilitation research; research and development; response

Each year, an estimated 1.7 million Americans suffer from traumatic brain injury (TBI). The incidence of TBI among veterans of the military may be as high as 30%, with blast injury from explosive devices causing the overwhelming majority of TBIs in combat settings. An association between non-severe (i.e., mild or moderate) mTBI and substance abuse has been demonstrated in numerous epidemiological studies. Therefore, veterans of the military that have experienced TBI during deployment or during non-deployed and civilian life may be at higher risk for drug abuse disorders than people that have not experienced TBI. However, despite extensive evidence of increased substance abuse disorder following non-severe TBI, little is known about how traumatic brain injury changes brain structure and function to make somebody more susceptible to drug abuse. Thus, there is a great deal of inconsistency in clinical treatments prescribed to non-severe TBI sufferers that can include no drug treatment, non-steroidal anti-inflammatory drugs, or even opioids. The long-term consequences for millions of veterans remains unknown. Advanced magnetic resonance imaging (MRI) techniques (e.g., diffusion tensor imaging) in humans have revealed subtle damage to brain tissues following mTBI, in which specific brain regions seem to be particularly vulnerable to injury. In our published data, an experimental model of blast mTBI in rodents led to an enduring inflammatory response that was evident in the medial prefrontal cortex (mPFC) of the brain, which was evident using advanced MRI techniques and pathological investigation. There is emerging evidence of a link between these types of inflammatory responses in the brain and drug abuse behavior. In fact, recent research has indicated that the use of opioids, which are commonly prescribed for TBI, initiate similar inflammatory responses. Therefore, our hypothesis is that drug intake and/or drug abuse relapse would be more likely following mTBI. Given that opioids are commonly administered to mTBI patients in emergency departments, combined with the fact that over 13 million Americans misused prescription pain killers or used heroin in 2016, this could lead to a significant public health issue with mTBI patients that are treated with opioids suffering from possible life-long issues with drug dependency. This study will explore the relationship between mTBI and substance abuse disorder using a laboratory model, wherein rodents will be exposed to blast mTBI and post-injury opioid self-administration to model individual drug treatment following injury. After removal of opioids, rodents will later be exposed again to opioid self- administration to identify relapse behaviors and addiction liability. The effects of pharmacological treatment on addiction liability will also be defined. The mechanisms for these changes in the brain following mTBI and opioid exposure will be determined using advanced MRI techniques and analysis of brain structure and chemistry. Results of this study may help to define a correlation between mTBI and substance abuse disorders that can be used by VA clinicians to better understand and treat veterans with drug addiction issues and history of TBI.

据估计，每年有170万美国人遭受创伤性脑损伤（TBI）。TBI的发病率 退伍军人中的死亡率可能高达30%，爆炸装置造成的爆炸伤 绝大多数创伤性脑损伤都发生在战斗环境中。非严重（即，轻度或中度） mTBI和药物滥用已在许多流行病学研究中得到证实。因此，退伍军人 在部署期间或非部署期间经历过TBI的军人和平民生活可能在 药物滥用障碍的风险高于没有经历过TBI的人。尽管广泛 非严重TBI后物质滥用障碍增加的证据，很少有人知道创伤性 脑损伤改变了大脑的结构和功能，使人更容易滥用药物。因此 在为非严重TBI患者规定的临床治疗中存在大量不一致性， 药物治疗，非甾体抗炎药，甚至阿片类药物。对数百万人的长期影响 退伍军人仍然未知。 先进的磁共振成像（MRI）技术（例如，扩散张量成像）在人类中具有 揭示了mTBI后脑组织的细微损伤，其中特定的脑区域似乎特别 容易受伤。在我们发表的数据中，啮齿动物中的爆炸mTBI实验模型导致了持久的 炎症反应，这是明显的内侧前额叶皮层（mPFC）的大脑，这是明显的 使用先进的MRI技术和病理学研究。有新的证据表明 这些类型的大脑炎症反应和药物滥用行为。事实上，最近的研究 表明使用阿片类药物（通常用于TBI）会引发类似的炎症反应。 因此，我们的假设是，药物摄入和/或药物滥用复发将更有可能在mTBI后。 鉴于阿片类药物通常在急诊科给予mTBI患者，结合 事实上，2016年有超过1300万美国人滥用处方止痛药或使用海洛因，这可能导致 使用阿片类药物治疗的mTBI患者可能终身患有严重的公共卫生问题， 药物依赖问题。 本研究将使用实验室模型探讨mTBI与物质滥用障碍之间的关系， 其中啮齿动物将暴露于冲击mTBI和损伤后阿片样物质自我给药以模拟个体药物 受伤后的治疗。在去除阿片类药物后，啮齿动物随后将再次暴露于阿片类药物自身， 管理，以确定复发行为和成瘾倾向。药物治疗对 成瘾责任也将被定义。mTBI和阿片类药物后脑中这些变化的机制 将使用先进的MRI技术和大脑结构和化学分析来确定暴露量。 这项研究的结果可能有助于确定mTBI和药物滥用障碍之间的相关性， VA临床医生使用它来更好地了解和治疗有毒瘾问题和TBI病史的退伍军人。