Severe Perinatal Hypoxic-Ischemic Brain Injury Induces Long-Term Sensorimotor Deficits, Anxiety-Like Behaviors and Cognitive Impairment in a Sex-, Age- and Task-Selective Manner in C57BL/6 Mice but Can Be Modulated by Neonatal Handling

Frontiers in Behavioral Neuroscience
Aida MuntsantLydia Giménez-Llort

Abstract

Perinatal brain injury (PBI) leads to neurological disabilities throughout life, from motor deficits, cognitive limitations to severe cerebral palsy. Yet, perinatal brain damage has limited therapeutic outcomes. Besides, the immature brain of premature children is at increased risk of hypoxic/ischemic (HI) injury, with males being more susceptible to it and less responsive to protective/therapeutical interventions. Here, we model in male and female C57BL/6 mice, the impact of neonatal HI and the protective effects of neonatal handling (NH), an early life tactile and proprioceptive sensory stimulation. From postnatal day 1 (PND1, modeling pre-term) to PND21 randomized litters received either NH or left undisturbed. HI brain damage occurred by permanent left carotid occlusion followed by hypoxia at PND7 (modeling full-term) in half of the animals. The behavioral and functional screening of the pups at weaning (PND23) and their long-term outcomes (adulthood, PND70) were evaluated in a longitudinal study, as follows: somatic development (weight), sensorimotor functions (reflexes, rods and hanger tests), exploration [activity (ACT) and open-field (OF) test], emotional and anxiety-like behaviors [corner, open-field and dark-light box...Continue Reading

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