Project 458186

Intracerebral hemorrhage (ICH) is a devastating bleed in the brain. The space occupied by the bleed (hematoma) and the accompanying swelling of the brain can increase pressure in the skull, with potentially fatal consequences. Despite women having an overall greater stroke burden than men, the majority of pre-clinical research is conducted using young, male rodents. These studies often fail to predict results in females, and suggest a critical lack of knowledge on sex differences in recovery after brain injury. We have recently discovered that following severe ICH, the uninjured brain shrinks in size. I hypothesize this exciting new phenomenon is a way for the brain to compensate for the increased volume of the bleed and brain swelling, both of which are associated with poor outcome. However, I believe this mechanism will be a double-edged sword, with excessive cell shrinkage leading to cellular damage that may negatively impact recovery. Estrogen is known to affect cell shrinkage (CS) in healthy cells and brain swelling after injury, making it of particular interest in the study of post-ICH CS. I will investigate whether male and female rats display different levels of CS following ICH. Secondly, I will deplete and augment estrogen levels in female rats to determine whether estrogen affects this process, mimicking changes in estrogen levels and common treatments for women (i.e., post-menopausal women, and women on oral contraceptives). In addition to analyzing cell volume, we will continuously measure pressure in the skull to relate to CS. Brain water content will be used to assess brain swelling. Mitochondrial health, which is important for intracellular energy production, will be used to assess damage from excessive shrinking, and behavioural tests will be used to assess functional outcome. Further understanding CS in a translationally relevant population will hopefully allow us to one day modulate this process to positively impact outcome in ICH patients.