Evaluation of Sex Differences in Vascular Density in a Rodent Model of Traumatic Brain Injury Using Steady‐State Contrast Enhanced Magnetic Resonance Imaging

Abstract

ObjectiveThe mechanisms by which female rats fare better then male rats post‐TBI remain unclear. Changes in vascular density and other measures of new blood vessel growth, angiogenesis, play a role in recovery post‐TBI. Vascular function has been hypothesized to be involved in sex differences in recovery post‐TBI. It is unknown if there are sex differences in injury induced changes in vessel density post‐TBI. The hypothesis was tested that females would have greater vessel density 48 hours post‐TBI than males, and that they would outperform males on motor coordination tasks one week after injury.MethodsAdult male and female rats were subjected to a severe TBI using a fluid percussion injury model. Steady‐state contrast enhanced MRI (SSC‐MRI, 15 mg/kg of ferumoxytol) was used to assess injured cortex vessel density in vivo 48 hours post‐injury. Motor coordination was assessed one week post‐injury using the balance beam.ResultsInjury and sex were a significant source of variation (p < 0.05) in regards to motor coordination performance. Injured male rats had a 2.4‐fold increase in beam traversal time (p < 0.05) as compared to male shams. No statistical difference was found between injured and sham females (p > 0.05). In regards to the SSC‐MRI results, 48 hours post‐ injury both sex and injury were a significant source of variation in vessel density within the ipsilateral cortex (p < 0.05). Injured males had a 0.84 fold decrease in vessel density as compared to male shams (p < 0.05). Injured females did not have a significant difference in vessel density as compared to female shams (p > 0.05).ConclusionsThe greater vessel density in injured females as compared to injured males may contribute to sex differences in motor coordination post‐TBI. SSC‐MRI could be used in future clinical studies in order to elucidate the temporal changes in cortical vessel density post‐TBI. A better understanding of sex differences in vascular responses post‐injury could aide in ensuring that the development of therapies targeting angiogenesis post‐TBI will be appropriate for both male and female patients.