Chronic Oxytocin treatment has long lasting therapeutic potential in a rat model of neonatal hypercapnic-hypoxia injury, through enhanced GABAergic signaling and by reducing hippocampal gliosis with its anti-inflammatory feature

Abstract

Previous studies have shown that, oxytocin has anticonvulsant and neuroprotective effects. One of the most important complications of Hypercapnic-hypoxia is drug resistance epilepsy. Effects of chronic intraperitoneal oxytocin treatment on gliosis, neuroinflammation and seizure activity was investigated in a model in which rats were exposed to hypoxia on postnatal day 1 and later challenged to the seizure-inducing pentylenetetrazol Forty pups were included in the study on their first day of birth. 16 pups were exposed to 100% CO₂ for 5 minutes and other 16 pups for 10 minutes. The remaining 8 pups comprised the control group. Groups were classified according to oxytocin administration within the first 4 weeks. Pentylenetetrazol was administered 6 months after the oxytocin treatment. The Racine's Convulsion Scale and onset times of first myoclonic jerk (FMJ) were evaluated. To determine the mechanisms by which oxytocin exerted its effects on hypercapnic-anoxia exposed rats, we performed CA1 total neuron count & CA1 GFAP immunostaining, and measured brain levels of TNF-α and GAD-67. The Racine scale and TNF-α values were significantly lower in both groups that received oxytocin, while time-to-FMJ and GAD-67 level were significantly higher. The histopathological evaluations showed that oxytocin had significant ameliorative effects (especially regarding gliosis) on the hippocampus of hypoxic rats. Regarding the results of present study, it can be speculated that after acute hypercapnic-anoxia exposure, chronic Oxytocin treatment has long lasting therapeutic potential on rats, possibly by reducing the gliosis with its anti-inflammatory feature and by activating the GABA pathway.

Keywords: CA1; GAD-67; Hypoxia; TNF-α; hippocampus; oxytocin; seizure.