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

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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.