How do astrocytes respond to traumatic brain injury across female lifespan?
Astrocytes play a critical role in the brain’s response to traumatic brain injury (TBI), and this response varies significantly across the female lifespan. Research into sex differences in TBI has traditionally focused on male, but emerging evidence suggests that females, despite often experiencing milder TBIs, may suffer more prolonged and severe consequences. These differences could be influenced by fluctuations in sex hormones like estrogen, progesterone, and testosterone, which change throughout a female’s life, particularly during the menstrual cycle, pregnancy, and menopause. Our research aims to explore how astrocytes, key regulators of brain function, respond to TBI at different hormonal stages in females, shedding light on how these fluctuations contribute to sex-dependent outcomes in neurodegeneration.
How does estrogen participate in blood-brain barrier susceptibility to injury?
Estrogen has been shown to influence the integrity of the blood-brain barrier (BBB), which protects the brain from harmful substances in the blood. In the context of TBI, BBB disruption can exacerbate brain injury and worsen outcomes. Studies suggest that estrogen can enhance BBB integrity by promoting tighter junctions between endothelial cells, which may be one reason why females, particularly during high-estrogen phases of their cycle, show a different response to TBI than males. Our research will investigate how astrocytes, which are crucial in maintaining BBB function, mediate estrogen’s effects on BBB permeability and how these hormonal influences contribute to sex-specific responses to brain injury.
Does human astrocytes respond to traumatic brain injury differently than mouse astrocytes?
There are significant differences in how human and mouse astrocytes respond to traumatic brain injury. While mouse models are essential for studying TBI and astrocyte biology, they may not fully replicate the human brain’s complexity and cellular responses. Studies have shown that astrocytes in humans and mice exhibit differences in morphology, gene expression, and their interactions with other brain cells, which may influence how they respond to injury. Understanding these species-specific differences is critical for translating findings from mouse models to human clinical outcomes, and our research will explore these disparities to improve the relevance of preclinical TBI studies and ultimately enhance patient care. In our lab, we will use chimeric mice with human astrocytes and study how human astrocytes respond to injury compared to mouse astrocytes. We will also study if the response in human female astrocytes differ from the one in human male astrocytes.