Systemic Hypoxia and the Depression of Synaptic Transmission in Rat Hippocampus after Carotid Artery Occlusion

Abstract

The relationship between step reductions in inspired oxygen and the amplitude of evoked field excitatory postsynaptic potentials (fEPSPs) recorded from hippocampal CA1 neurons was examined in anaesthetized rats with a unilateral common carotid artery occlusion. The amplitudes of fEPSPs recorded from the hippocampus ipsilateral to the occlusion were significantly more depressed with hypoxia than were the fEPSPs recorded from the contralateral hippocampus. The adenosine A1‐selective antagonist, 8‐cyclopentyl‐1,3‐dimethylxanthine (8‐CPT), blunted the hypoxic depression of the fEPSP. Tissue partial pressure of oxygen (Ptiss,O2) was measured in the ipsilateral and contralateral hippocampus using glass Clark‐style microelectrodes. Ptiss,O2 fell to similar levels as a function of inspired oxygen in the ipsilateral and contralateral hippocampus, and in the ipsilateral hippocampus after administration of 8‐CPT. Hippocampal blood flow (HBF) was measured using laser Doppler flowmetry. A decline in HBF was associated with systemic hypoxia in both hippocampi. HBF, as a function of inspired oxygen, fell significantly more in the ipsilateral than in the contralateral hippocampus. We conclude that endogenous adenosine acting at the neuronal A1 receptor plays a major role in the depression of synaptic transmission during hypoxic ischaemia. The greater susceptibility of the fEPSP in the ipsilateral hippocampus to systemic hypoxia cannot be explained entirely by differences in Ptiss,O2 or HBF between the two hemispheres.

Exercise-Induced Elevated BDNF Level Does Not Prevent Cognitive Impairment Due to Acute Exposure to Moderate Hypoxia in Well-Trained Athletes

“…One reason which at least theoretically might be considered for the acute action of BDNF is its involvement in synaptic transmission [ 91 ]. The results from animal studies indicate that during hypoxia neurons can within minutes alter synaptic transmission [ 92 , 93 ]. Support for a link between exposure to hypoxia and run-down of synaptic transmission has been widely documented in in vitro studies [ 94 , 95 ] and in rats subjected to severe (6100 m) hypoxia [ 96 ].…”

Hypoxic changes in the central nervous system of noise-exposed mice

“…The hippocampal formation is particularly vulnerable to stress and ischemia [14,15], and the hippocampus is known to be susceptible to hypoxia. The stress of noise exposure may increase mouse hippocampal acetylcholine esterase activity and result in alterations to the cholinergic system [16].…”

Alterations of CaMKII after hypoxia‐ischemia during brain development

“…Furthermore, persistent CaMKII depletion from the cytoplasm, and its inactivation in the late phase of reperfusion after HI as shown by its dephosphorylation, may bring CaMKII-mediated events to a standstill, resulting in interruption of synapse development, synaptic remodeling and plasticity. Synapse transmission is severely damaged in HI-affected brain regions (Fowler et al 2003). Without proper synaptic connections, developing neurons may undergo apoptosis (Oppenheim 1991;Mennerick and Zorumski 2000;Lossi et al 2002;Blomgren et al 2003).…”