Microglial activation and neural stem cells cross talk post TBI

Dr. Samia Khoury

Start: May 01, 2017

End: Apr 01, 2019

Abstract

Mild Traumatic Brain Injury (mTBI) is the most common type of head injury and results in neurologic and cognitive deficits especially in attention and memory. Microglia, the central nervous system resident immune cells become activated after TBI in a normal response to clear injured cells. Persistent inflammation can lead to neurologic deficits partly attributable to impaired neurogenesis. Neurogenesis refers to the generation of new neurons from endogenous stem cells. This process takes place in specialized brain regions such as the subventricular zone and hippocampus, and is linked to learning and memory. We hypothesize that microglia play an important role in TBI and they can be beneficial or damaging depending on their state of activation. In this proposal, we will explore how TBI leads to activation of microglia (inflammation), and how chronic activation of microglia impairs neurogenesis, leading to behavioral deficits. The objectives of this study are:  To characterize the role of microglial activation at different time points after an experimental TBI using mouse models of mild and severe TBI. We will examine the distribution and timing of microglia activation anatomically and molecularly. Further, we will assess the effect of TBI on neural stem cells (NSCs) multiplication and differentiation in live animals and the mechanism of microglial effects on NSCs. Finally; the behavioral deficits post severe and mild TBI including spontaneous object and location recognition memory and relate the outcomes with neural injury and inflammatory markers.

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