[ ³ H]Muscimol Binding to γ-Aminobutyric Acid _A Receptors Is Upregulated in CA1 Neurons of the Gerbil Hippocampus in the Ischemia-Tolerant State

Abstract

Background and Purpose-Excitotoxic activation of glutamate receptors is currently thought to play a pivotal role in delayed neuronal death (DND) of highly vulnerable CA1 neurons in the gerbil hippocampus after transient global ischemia. Postischemic degeneration of these neurons can be prevented by "preconditioning" with a short sublethal ischemic stimulus. , and the dentate gyrus were analyzed in 2 experimental paradigms. Gerbils were subjected to (1) a 5-minute ischemic period resulting in DND of CA1 neurons and (2) a 2.5-minute period of ischemia mediating tolerance induction. Results-[3 H]MK-801 and [ 3 H]AMPA binding values to excitatory NMDA and AMPA receptors showed a delayed decrease in relatively ischemia-resistant CA3 and dentate gyrus despite maintained neuronal cell density. [3 H]Muscimol binding to GABA A receptors in CA1 neurons was transiently but significantly increased after preconditioning but not after global ischemia with consecutive neuronal death. Conclusions-Downregulation of ligand binding to glutamate receptors in relatively ischemia-resistant CA3 and dentate gyrus neurons destined to survive suggests marked synaptic reorganization processes despite maintained structural integrity. More importantly, upregulation of binding to inhibitory GABA A receptors in the hippocampus indicates a relative shift between inhibitory and excitatory neurotransmission that we suggest may participate in endogenous postischemic neuroprotection.

Successful Regeneration After Experimental Stroke by Granulocyte-Colony Stimulating Factor Is Not Further Enhanced by Constraint-Induced Movement Therapy Either in Concurrent or in Sequential Combination Therapy

“…Therefore, to get an impression of the net shift in the balance between excitatory glutamate and the inhibitory GABA A Figure 6). 19 This approximation resulted in a surprisingly specific pattern of binding densities, which correlated with failure in significant functional recovery, that is, CIMT treatment tended to be associated with a shift toward inhibition in most regions analyzed. This finding is well in line with results from our recent study comparing postischemic receptor regulation after CIMT and brain-derived neurotrophic factor treatment.…”

Regulation of extracellular glutamate levels in the long-term anoxic turtle striatum: coordinated activity of glutamate transporters, adenosine, KATP+ channels and GABA

“…The preservation of neuronal network integrity is a prerequisite for functional recovery and perhaps glutamate has a vital role here. Many synaptic connections are dependant on glutamate [31]. If some degree of continued glutamate release is essential to the turtle, it is also likely to be so for the mammal.…”

Ischemic preconditioning ameliorates excitotoxicity by shifting glutamate/γ‐aminobutyric acid release and biosynthesis

“…Antiexcitotoxic, antiinflammatory, and antiapoptotic mechanisms are some of the key mechanisms for the observed protection in preconditioned models (Dirnagl et al, 2003). Recent evidence suggests that a shift between inhibitory and excitatory neurotransmission may be an important mechanism by which ischemic preconditioning promotes protection (Grabb et al, 2002;Sommer et al, 2002Sommer et al, , 2003.…”

“…Postsynaptically, IPC appears to enhance inhibitory pathways, in that it promotes an up-regulation of GABA A receptors in the hippocampus (Sommer et al, 2002). These results are indicative of a relative shift from excitatory to inhibitory neurotransmission after IPC that may promote ischemic tolerance.…”