Effects of Acute Perinatal Asphyxia in the Rat Hippocampus

Abstract

In the present work, we have used a rat animal model to study the early effects of intrauterine asphyxia occurring no later than 60 min following the cesarean-delivery procedure. Transitory hypertonia accompanied by altered posture was observed in asphyxiated pups, which also showed appreciably increased lactate values in plasma and hippocampal tissues. Despite this, there was no difference in terms of either cell viability or metabolic activities such as oxidation of lactate, glucose, and glycine in the hippocampus of those fetuses submitted to perinatal asphyxia with respect to normoxic animals. Moreover, a significant decrease in glutamate, but not GABA uptake was observed in the hippocampus of asphyctic pups. Since intense ATP signaling especially through P2X(7) purinergic receptors can lead to excitotoxicity, a feature which initiates neurotransmission failure in experimental paradigms relevant to ischemia, here we assessed the expression level of the P2X(7) receptor in the paradigm of perinatal asphyxia. A three-fold increase in P2X(7) protein was transiently observed in hippocampus immediately following asphyxia. Nevertheless, further studies are needed to delineate whether the P2X(7) receptor subtype is involved in the pathogenesis, contributing to ongoing brain injury after intrapartum asphyxia. In that case, new pharmacologic intervention strategies providing neuroprotection during the reperfusion phase of injury might be identified.

Pathophysiology of perinatal asphyxia: can we predict and improve individual outcomes?

“…Indeed, a decrease in glutamate uptake has been observed in the hippocampus of rat pups subjected to 15 min of PA [148] and a similar result has been observed in the cortex, basal ganglia and thalamus of piglets [149]. Reduced glutamate uptake is correlated with a down-regulation of astrocytic excitatory amino acid transporters EAAT-1 and EAAT-2 [150] after HI, reinforcing the idea that energy deficits also promote a severe disruption of astrocytic cell function.…”

Environmental Enrichment Decreases Asphyxia-Induced Neurobehavioral Developmental Delay in Neonatal Rats

“…In the background, several biochemical and morphological alterations have been described. Among others, changes in neurotransmitter levels and metabolic parameters have been found in the hippocampus and cerebral cortex [41–43]. Delayed cell death, fiber sprouting and changes in postsynaptic densities have also been found in the hippocampus [29,30,44].…”

P2X7 receptors in cerebral ischemia

“…Besides, a transient and significant enhancement in P2X 7 protein expression was reported to occur immediately after asphyxia in a rat model of intrauterine asphyxia [32] .…”

“…Possibly, the activation of P2X 7 Rs simultaneously opens both cation channels permeable to large cations and anion channels permeable to organic anions such as L-glutamate and D-aspartate, mediating rapid non-vesicular glutamate release [26] . In a study of perinatal acute asphyxia, glutamate was verified to be released via the P2X 7 R channel [32] .…”

“…Excessive extracellular glutamate even forms a feedback loop and further down-regulates P2X 7 Rs [32] . It is noteworthy that this loop may represent a cellular effort to counteract and possibly halt the detrimental outcome of progressive neuronal damage.…”