TRAUMATIC BRAIN INJURY (TBI)
TBI can be characterized by alterations in brain immune signaling, which are associated with physiologic and cognitive changes. We are interested in understanding the relationship between these immune changes and their role in driving poor outcomes.
TBI is a brain dysfunction caused by an outside force to the head. It is among one of the most heterogenous neurological disorders due to the number of pathophysiological changes that occur (e.g. neuroinflammation, blood brain barrier disruption, and neuronal death). 80% of TBI are considered mild, and 15% of these patients have difficulty recovering. They experience chronic somatic, emotional, and behavioral changes that last for years. Studies have associated neuroinflammation with these long-term deficits identified in patients. Neuroinflammation is characterized by the activation of microglia cells (Iba1), release of pro-inflammation cytokines, and dysregulation of immune signaling pathways (MAPK, NF-κB). Researchers believe that understanding and targeting these immune changes can lead to fast recovery.
Systems Analysis of Neuroinflammatory Signaling in Mice after Repeated Mild TBI (rmTBI)
Role of neuronal p38 MAPK after repetitive mild TBI
Repeated mild TBI causes long-term cognitive deficits in mice despite no overt neuronal damage. Our lab is interested in identifying mechanisms driving these long-term cognitive deficits found in repeated mild TBI (rmTBI). Through a collaboration with the Buckley Lab, we studied the relationship between cerebral blood flow (CBF) and various immune signaling pathways. It was discovered that low CBF was a marker for long-term cognitive deficits and that various pro-inflammatory cytokines (Iba1, TNF-alpha) were correlated with low CBF. These pro-inflammatory cytokines and immune intracellular signaling pathways (p38 MAPK and NF-κB) were also colocalized in neurons. Based on these findings, we hypothesized that rmTBI stresses the neurons, promoting stress-response pathway activation, such as p38 MAPK. These pathways induce the expression of cytokines that lead to microglial activation, changes in CBF, and ultimately cognitive impairment.
More information can be found in the articles on the right.
Figure 1. Inverse relationship between Iba1 expression and cerebral blood flow (CBF). Sankar et al. 2018. Neurobiology of Disease
PUBLICATIONS
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*Sankar, S.¨, Pybus, A.¨, Liew, Y., Sanders, B., Shah, K., Wood, L.†, Buckley, E. †, 2019. Low cerebral blood flow is a non-invasive biomarker of neuroinflammation after repetitive mild traumatic brain injury, Neurobiology of Disease., 124: 544-554.
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*Brothers R. ¨, Bitarafan, S.¨, Pybus, A., Wood, L.†, Buckley, E.†, 2021. Systems analysis of the neuroinflammatory and hemodynamic response to traumatic brain injury, Journal of Visualized Experiments, in press [publication delayed due to COVID-19].
