Behavioral effects of cardiac arrest in mice

小鼠心脏骤停的行为影响

• 批准号: 7534272
• 负责人: Anne Courtney DeVries
• 金额: $ 16.07万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7534272
• 关键词: Affect; Alzheimer' s Disease; Antibiotics; Anxiety; Applications Grants; Behavior; Behavioral; Behavioral Paradigm; Bone Marrow; Brain; Cardiopulmonary Arrest; Cardiopulmonary Resuscitation; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chronic stress; Clinical; Corticosterone; Craniocerebral Trauma; Data; Disease; Event; Exposure to; Foundations; Glucocorticoid Receptor; Heart Arrest; Individual Differences; Inflammation; Injury; Ischemia; Length; Measures; Mental Health; Microglia; Minocycline; Mus; Nerve Degeneration; Neurobiology; Neurons; Outcome; Parkinson Disease; Pathogenesis; Personal Satisfaction; Pharmaceutical Preparations; Physiological; Risk Factors; Stress; Testing; Thinking; acute stress; base; cohort; immune function; insight; prevent; psychologic; response

DESCRIPTION (provided by applicant): Neuroimmune activation is a common consequence of ischemia, but the behavioral ramifications are not well-described. The studies proposed in this grant application will provide a neurobiological foundation on which to study the effects of microglial activation on anxiety following cardiac arrest and cardiopulmonary resuscitation (CA/CPR). The interaction between exposure to stress and microglial activation also will be examined. It is well-established that stress can have long-term physiological and psychological consequences. Our overall hypothesis is that microglial activation following CA/CPR is exacerbated by prior exposure to stress and is directly responsible for increased anxiety. The specific hypotheses that we will test in mice are (1) that treatment with exogenous microglia will increase measures of microglial activation and anxiogenic-like behavior, while treatment with minocycline (an antibiotic) following CA/CPR will decrease microglial activation and anxiogenic-like behavior, 2) that chronic stress will be more effective than acute stress in activating microglia and increasing anxiogenic-like behavior following CA/CPR, and 3) that prior exposure to stress increases microglial activation and anxiogenic responses to CA/CPR via increased corticosterone concentrations acting through glucocorticoid receptors. Thus, we propose that altering the neuroimmune response to CA/CPR can affect behavior and potentially contribute to neuronal death. Because microglial activation is thought to contribute to neural degeneration in a variety of CMS disorders, including ischemic injury, head trauma, Alzheimer disease, and Parkinson disease, the data from the present proposal may have broad implications.

描述（由申请人提供）：神经免疫激活是缺血的常见后果，但其行为后果尚未得到充分描述。这项研究将为研究小胶质细胞激活对心脏骤停和心肺复苏（CA/CPR）后焦虑的影响提供神经生物学基础。暴露于压力和小胶质细胞激活之间的相互作用也将被检查。众所周知，压力会产生长期的生理和心理后果。我们的总体假设是，CA/CPR后的小胶质细胞激活因先前暴露于压力而加剧，并直接导致焦虑增加。我们将在小鼠中检验的具体假设是：（1）用外源性小胶质细胞治疗将增加小胶质细胞活化和致焦虑样行为的测量，而用米诺环素治疗将增加小胶质细胞活化和致焦虑样行为的测量，2）在CA/CPR后，慢性应激在激活小胶质细胞和增加焦虑样行为方面比急性应激更有效，和3）先前暴露于应激通过增加的皮质酮浓度通过糖皮质激素受体作用而增加小胶质细胞活化和对CA/CPR的致焦虑反应。因此，我们认为改变对CA/CPR的神经免疫反应可以影响行为并可能导致神经元死亡。由于小胶质细胞激活被认为有助于多种CMS疾病（包括缺血性损伤、头部创伤、阿尔茨海默病和帕金森病）的神经退行性变，因此本提案的数据可能具有广泛的影响。