Revealing sex-specific molecular changes in hypoxia-ischemia induced neural damage and subsequent recovery using zebrafish model

Functional recovery from hypoxia-ischemia depends on an individual's response to the ischemic damage and recovery. Many of the neurological disorders, including cerebral stroke have sex-specific characteristics. Deciphering the differential molecular mechanisms of sex-specific recovery from hypoxic-ischemic insult can improve medical practice in the treatment of cerebral stroke. In the present study, we describe the establishment of a sex-specific global hypoxia-ischemia neural damage and repair model in zebrafish. During hypoxic exposure a delayed behavioural response was observed in female fish that resumed normal swimming pattern earlier than their male counterparts. Moreover, female appeared more affected as they showed restricted locomotor and exploratory behaviour in novel tank test, reduced mitochondria] enzyme activity, enhanced DNA damage, and cell death after hypoxia insult. However, they showed a faster recovery as compared to male. Analysis of mRNA and protein expression levels of some characteristic hypoxic-ischemic markers showed notable sex-specific differences. Using zebrafish model, we have uncovered cellular and molecular differences in sex-specific systemic responses during the post-hypoxia recovery. This insight might help in devising better therapeutic strategy for stroke in female patients.