Female gonadal hormone effects on microglial activation and functional outcomes in a mouse model of moderate traumatic brain injury

Abstract

AIMTo address the hypothesis that young, gonad-intact female mice have improved long-term recovery associated with decreased neuroinflammation compared to male mice.METHODSEight to ten week-old male, female, and ovariectomized (OVX) mice underwent closed cranial impact. Gonad-intact female mice were injured only in estrus state. After injury, between group differences were assessed using complementary immunohistochemical staining for microglial cells at 1 h, mRNA polymerase chain reaction for inflammatory markers at 1 h after injury, Rotarod over days 1-7, and water maze on days 28-31 after injury.RESULTSMale mice had a greater area of injury (P = 0.0063), F4/80-positive cells (P = 0.032), and up regulation of inflammatory genes compared to female mice. Male and OVX mice had higher mortality after injury when compared to female mice (P = 0.043). No group differences were demonstrated in Rotarod latencies (P = 0.62). OVX mice demonstrated decreased water maze latencies compared to other groups (P = 0.049).CONCLUSIONDifferences in mortality, long-term neurological recovery, and markers of neuroinflammation exist between female and male mice after moderate traumatic brain injury (MTBI). Unexpectedly, OVX mice have decreased long term neurological function after MTBI when compared to gonad intact male and female mice. As such, it can be concluded that the presence of female gonadal hormones may influence behavioural outcomes after MTBI, though mechanisms involved are unclear.

Reward and immune responses in adolescent females following experimental traumatic brain injury

“…As such, our analysis with fibrinogen demonstrated acute sex-specific neuroprotection to BBB compromise. The above is corroborated by Umeano and colleagues in which following a closed-head injury model, the effect of BBB protection in females was diminished with the absence of sex hormones as a result of ovariectomy [43]. Together with our behavioral data, this finding implies that it is not necessarily the injury parameters that are responsible for inducing sex-specific effects of TBI-induced neuroinflammation, but rather the sex-specific biological response to injury that can account for differences observed.…”

Diacylglycerol Lipase-β Knockout Mice Display a Sex-Dependent Attenuation of Traumatic Brain Injury-Induced Mortality with No Impact on Memory or Other Functional Consequences

“…The finding that female DAGL-b + / + mice showed high TBI survival rates is consistent with female rodents being generally protected from TBI-induced mortality compared with males. 39,40 The high rate of survival in female mice indicates that DAGL-b plays a sex-dependent role. Although the mechanisms underlying female protection from TBI mortality remain unclear, in this study, we consider several possibilities.…”