Title

Sex Differences in a Rodent Model of Early Hypoxic-Ischemic Brain Injury: The Female Advantage

Date of Completion

January 2011

Keywords

Psychology, Behavioral Sciences

Degree

Ph.D.

Abstract

Neurological impairments secondary to oxygen deprivation, including hypoxia/ischemia (HI) associated with immaturity of vasculature and pulmonary autoregulation in premature and very low birthweight (VLBW) infants, as well as HI events relating to birth (e.g., cord prolapse), comprise one of the most common causes of damage to the infant brain. Affected children are in turn prone to cognitive deficits, including language and learning disabilities. Severity of injury and further pathological outcome has also been found to be dependent upon sex, with more substantial long-term deficits seen for male infants, even when male and female infants are matched for degree of injury. Although the cause(s) of these sex differences are unknown, evidence has indicated hormonal and genetic components may influence the severity of—and long-term outcome following—HI injury. Within the studies presented here, we have assessed behavioral outcome in a rodent model of neonatal HI, and as seen in the clinical data, we have reported sex differences in both rapid auditory processing and spatial learning following HI injury (more severe deficits seen in HI male rats). Our results implicate the role of neonatal testosterone, differences in apoptotic cascades, and X-linked inhibitors of apoptosis in the disparity of injury seen between males and females following early brain damage. These results indicate significant differences in the extent of pathology as measured by behavioral outcome between the sexes (conceivably by an interaction of hormones and innate differences in cell death pathways following perinatal HI) and have far reaching implications for future research on gender differences in response to early brain injury, including the possible implementation of gender-specific neuroprotectants in clinical practice. ^