Microglial morphological changes following neuronal p38α knockout in repetitive traumatic brain injury
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Anbuchelian, Adhrija
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Abstract
Mild traumatic brain injury (mTBI) is defined as a physical impact to the head causing internal injuries to the brain and nervous system. Rather, it is considered a primary mechanical injury that triggers a secondary chemical injury cascade within the nervous system. While current therapies for mTBI focus on alleviating symptoms, there is still a lack of understanding of the underlying mechanisms that cause the internal cascade of injuries that we see. Studies suggest that, following an mTBI, a downstream cascade of pro-inflammatory signaling pathways and cytokines are released, leading to long-term neural deficits. One example of such a pathway is the p38α mitogen-activated protein kinase (MAPK) pathway. Glial cells are also an important point of focus when looking into internal injury markers after mTBI. Particularly, microglia are shown to be activated upon injury to the brain. Previous studies have shown that p38 MAPK signaling can impact the release of proinflammatory cytokines, activation of microglia, and promote internal injury states, but the main mechanism of how such modulation occurs is unclear. This study aims to understand the relationship between inhibiting p38 MAPK via Cre-mediated recombination and the resulting inflammatory response using mice that have been exposed to a weight drop model mimicking rmTBI. Given its known links to neuroinflammation and synaptotoxicity, we targeted the p38α (MAPK14) isoform using a tamoxifen-inducible knockout model. Immunohistochemistry was used to stain for microglia and to analyze different morphological characteristics of the microglia. This study demonstrated that rmTBI induces changes in microglial morphology that are highly dependent on both sex and neuronal p38α signaling, with effects that do not consistently align with the classical model of microglial activation. These findings highlight the complexity of neuroinflammatory responses following injury and offer insight into potential therapeutic strategies for TBI and related neurodegenerative conditions.
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2026-05
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Text
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Undergraduate Thesis