Investigation of behavioral characteristic changes in animals with varying injury severity following brain tissue damage in a mouse model of neonatal hypoxia-ischemia during the juvenile period

Introduction: Neonatal hypoxia-ischemia (HI) remains one of the most significant causes of perinatal central nervous system injuries and subsequent neurodevelopmental disorders. The development of new therapeutic interventions requires improvements in existing methods for assessing clinical status according to the severity of the pathological process, enabling more precise evaluation of disease correction. Materials and Methods: Neonatal hypoxia-ischemia was modeled in CD-1 mice at 9 days of age (n=51). Motor and coordination impairments were assessed using the inverted grid, vertical pole, and horizontal pole tests on days 7 and 14. Anxiety-like behavior and exploratory activity were evaluated in the open field test on day 15. Neurophysiological reactivity was examined by administering caffeine (20 mg/kg) one hour prior to the Open field test on day 16. Results: A statistically significant difference in motor activity was observed between the mild and moderate injury groups compared to the intact group, with reductions of 37% and 57% in the inverted grid test and 27% and 53% in the vertical pole test, respectively. Pharmacological challenge with caffeine stimulated a 1.5-fold increase in speed and distance travelled in the moderate injury group compared to those in the intact group, despite baseline statistically significant differences in the Open field test. Conclusion: The experimental approach to assessing the clinical status of animals after neonatal hypoxia-ischemia modeling, followed by stratification based on injury severity, revealed statistically significant differences across multiple parameters between the studied groups.