Application of Cortexin for correcting the consequences of hypoxic-ischemic damage in the brain of infant rats

Abstract

To verify if the peptide preparation Cortexin can be used to correct pathological processes in the CNS during perinatal ontogenesis, a set of physiological parameters (EMG, ECG, respiration, vagosympathetic balance) were recorded and analyzed in a rat perinatal hypoxic-ischemic brain damage (PHIBD) model and control infant rats. In experimental 7-day-old animals, PHIBD was modeled under inhalation ether anesthesia by ligation of the left common carotid artery and subsequent exposure to a gas mixture of 8% oxygen and 92% nitrogen. 1 h after exposure, animals were first injected intraperitoneally with cortexin (1 mg/kg); the preparation was then injected at a daily basis for 10 days. Both control animals and those after surgery but non-treated were injected with physiological solution. After 10 and 30 days after surgery, animals exhibited a delayed body weight gain versus control and significant differences in EMG intensity and spectral structure. Cortexin treatment induced on day 10 a transient improvement in EMG spectral structure but not amplitude; by day 30, the positive effect of cortexin was no longer observed. The respiration rate both in treated and non-treated animals was higher than in control. No significant changes in the heart rate were revealed in animals with PHIBD, but non-treated animals exhibited on day 30 a tendency towards its decrease. The heart rate variability (HRV) analysis showed that 10 days after trauma both non-treated and cortexin-treated animals exhibited a statistically significant shift in the vagosympathetic balance towards a parasympathetic prevalence. On day 30, cortexin treatment yields positive effects, while in non-treated animals the vagosympathetic balance shifts towards a humoral-metabolic and sympathetic prevalence. Cortexin injection to intact rats leads to significant disturbances in the vagosympathetic balance, cardiac and, to a lesser extent, respiratory rhythms, and can cause stable disturbances in activity of the somatic and vegetative nervous systems.