Neurotropic Effects of Cortexin on Models of Mental and Physical Developmental Delay

Objective: To evaluate the efficacy of the neurotropic action of cortexin in models of mental and physical developmental delays in rat offspring. Methods: The neurotropic properties of bovine brain cortex polypeptides were studied using two models of mental and physical developmental delays in rats: toxic CNS damage (oral administration of ethanol during the last week of pregnancy) and neonatal trauma (ischemia-hypoxia). The drug was administered intramuscularly or rectally as suppositories for 20 days. Treatment efficacy was evaluated using the mNSS scale, open field, rotarod, and adhesive removal tests. A histological examination of the brain was subsequently performed. In a separate series of experiments in mice, the concentration of the test drug cortexin and the reference drug cerebrolysin was determined in blood and brain tissue samples using radioactive iodine (Na125I) labeling of these preparations. Results: Modeling developmental delay in rat offspring (due to the toxic effect of ethanol in late pregnancy or neonatal trauma) led to pronounced neurological deficits, manifested by decreased motor activity, and sensorimotor, and coordination disorders. Administration of cortexin in all forms reduced the severity of neurological deficits as measured by mNSS scores, improved motor activity in the Open Field test, enhanced performance in the Adhesive Removal and Rotarod tests, and decreased structural changes in brain tissues. Histological examination revealed reduced neuronal damage in multiple cortical regions, with a significant increase in normal, unchanged neurons compared to placebo groups. Comparison of the blood concentrations of labeled Na125I cortexin depending on the type of administration showed similar distribution profiles in brain tissues, primarily dependent on its blood concentration, which was influenced by the route of administration. Conclusions: The results indicate that brain polypeptides (cortexin), administered either intramuscularly or rectally, can reach the systemic circulation and cross the blood-brain barrier, as demonstrated by our distribution studies using radiolabeled preparations. These polypeptides exert comparable neurotropic effects in models of mental and physical developmental delays in offspring caused by neonatal trauma or the toxic effect of ethanol in late pregnancy in rats.