engleski

Lifelong changes in cingulate cortex and learning behavior after moderate perinatal hypoxia in the rat

Aiming to find molecular, cellular, and structural brain hallmarks and related behavioral outcome after perinatal hypoxia, we designed a non- invasive model of perinatal hypoxia in the newborn rats. In the randomized study, fifty-two Wistar Han rats were subjected to general hypoxia (pO2 73mmHg/2h) or normoxia, 24h after birth. The Western blot method applied 2h, 8h, 12h, and 24h later, showed a gradual increase of the hypoxia- inducible factor 1α, and a decrease of the cytochrome-C- oxygenase (subunit 4, isoform 1) expression, revealing moderate brain lesion in the rats subjected to hypoxia. The behavioral testing at 30th and 70th postnatal days, using open field, hole board, social choice, and T-maze paradigm displayed significant hyperactivity and slower pace of learning in the rats that were exposed to perinatal hypoxia. The closer examination of the cingulate cortex at the age of 4 months, by WFA- and anti-parvalbumin immunohistochemistry, disclosed a significantly increased number of perineuronal nets and parvalbumin-interneurons in the medial and retrosplenial areas. Thus, the moderate hypoxia in the newborn rats causes lifelong changes at the molecular and connectivity level in the cingulate cortex and related behavioral outcome. This new, non- invasive perinatal brain lesion in rats, according to the findings obtained, successfully resembled a frequent but diagnostically neglected moderate perinatal brain injury in humans and may establishes as a complementary model for future search for prevention, diagnostic and therapeutic strategies for perinatal brain injuries in human.

hypoxia ; brain development ; perineuronal nets ; learning

nije evidentirano