The long-term goal of this research is to understand the (patho) physiologic role of the inhibitory neuromodulator adenosine in the brain's early resp0onse to stroke. Understanding adenosine's contribution is important because adenosine-based pharmacological interventions show promise in reducing neuronal hypoxic/ischemic injury in a number of animal models [31,34,83,87,117]. The specific focus if this proposal is to extend to an in vivo model of the PI's previous series of studies performed in the in vitro hippocampal slice. These in vitro studies detailed adenosine's substantial mediation of the early reversible depression of synaptic transmission and adenosine's interaction with the anoxic depolarization in response to ischemic-like conditions [39-42,44]. Surprisingly, in spite of an extensive literature describing adenosine's role I in vitro slice preparations [9,24,52,69,89,90,142], there has yet to be, to the best of our knowledge, a demonstration of adenosine's role in vivo. The following specific aims, therefore, focus on examining the contribution of salient observations made in vitro to an in vivo hypoxic/ischemic rat hippocampal model. The following specific aims will be addressed:
Specific Aim 1. Determine the role of adenosine receptors in the in the early hypoxic/ischemic depression of synaptic transmission in vivo.
Specific Aim 2. Examine the relationship between adensone receptor activation, inhibition of evoked synaptic potentials and tissue pO2 in vivo.
Specific Aim 3. Determine the influence of adenosine receptor activation on development of the anoxic depolarization during extended hypoxia/ischemia in vivo. And, examine adenosine receptor function in the post-ischemic period after the anoxic depolarization.
|Gervitz, L M; Davies, D G; Omidvar, K et al. (2003) The effect of acute hypoxemia and hypotension on adenosine-mediated depression of evoked hippocampal synaptic transmission. Exp Neurol 182:507-17|
|Fowler, J C; Gervitz, L M; Hamilton, M E et al. (2003) Systemic hypoxia and the depression of synaptic transmission in rat hippocampus after carotid artery occlusion. J Physiol 550:961-72|
|Gervitz, Leon M; Nalbant, Demet; Williams, Simon C et al. (2002) Adenosine-mediated activation of Akt/protein kinase B in the rat hippocampus in vitro and in vivo. Neurosci Lett 328:175-9|