Mediating role of corticotropin-releasing hormone (CRH) and opioid peptides in ischemia: behavioural and physiological correlates

神经元变性在心脏骤停或中风后的永久性心理、认知和身体后遗症中起主要作用。 主要旨在阻断缺血后钙介导的去极化和谷氨酸兴奋毒性的治疗方法都伴随着不希望的副作用，这阻碍了它们在临床环境中的使用。 因此，对能够安全有效地改变缺血诱导的神经元变性的治疗的开发的研究仍在继续。 有趣的是，越来越多的证据表明内源性肽能信号可能发挥神经保护作用。 本研究的主要目的是进一步研究阿片肽和CRH肽在介导缺血诱导的神经元损伤的生理级联反应中的作用。 与全脑缺血损伤相关的海马损伤引起许多行为和认知变化，主要特征是动物和人类的记忆障碍。 因此，评估推定的神经保护性化合物的一个关键组成部分是它们逆转缺血诱导的功能损伤以及神经元损伤的能力。 在表征不同肽信号的贡献时，我的研究还旨在使用各种测试来确定针对这些系统的治疗对缺血诱导的行为和记忆障碍的影响。 希望结合细胞和分子研究结果的行为评估可以帮助我们扩大对CRH和阿片肽在缺血中的作用的理解，并评估它们在开发新的治疗策略中的潜在价值。

Neuronal degeneration plays a major role in permanent psychological, cognitive and physical sequelae following cardiac arrest or stroke.  Therapeutic approaches mainly aimed at blocking calcium-mediated depolarization and glutamate excitotoxicity following ischemia have all been accompanied by unwanted side effects, which have prevented their use in clinical settings.  Thus, the search for the development of treatments able to safely and efficiently alter ischemia-induced neuronal degeneration continues.  Interestingly, evidence is beginning to accumulate suggesting that endogenous peptidergic signals may exert neuroprotective actions.  The principal objective of my research is to further characterize the involvement of opioid and CRH peptides in the physiological cascade mediating ischemia-induced neuronal damage.  The hippocampal damage associated with global ischemic insults provokes a number of behavioural and cognitive changes, mainly characterized by memory impairments in both animals and humans.  Thus, a critical component of the evaluation of putative neuroprotective compounds is their ability to reverse ischemia-induced functional impairments as well as neuronal damage.  In the characterization of the contribution of distinct peptide signals, my research also aims to determine the impact of treatments targeting these systems on ischemia-induced behavioural and memory impairments, using various tests.  It is hoped that behavioural assessments combined with cellular and molecular research findings can help broaden our understanding of the role of CRH and opioid peptides in ischemia, and evaluate their potential value in the development of new therapeutic strategies.