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Depletion of microglia immediately following traumatic brain injury in the pediatric rat: Implications for cellular and behavioral pathology.

Authors :
Hanlon, Lauren A.
Raghupathi, Ramesh
Huh, Jimmy W.
Source :
Experimental Neurology. Jun2019, Vol. 316, p39-51. 13p.
Publication Year :
2019

Abstract

The inflammatory response is a significant component of the pathophysiology of pediatric traumatic brain injury. High levels of inflammatory mediators have been found in the cerebrospinal fluid of brain-injured children which have been linked to poor prognosis. Targeting aspects of the inflammatory response in the hopes of finding a viable post-injury therapeutic option has gained attention. Microglia are largely responsible for perpetuating the injury-induced inflammatory response but in the developing brain they play beneficial roles in both normal and disease states. Following closed head injury in the neonate rat, depletion of microglia with intracerebral injections of liposomes containing clodronate was associated with an increase in neurodegeneration in the early post-injury period (3 days) relative to those injected with empty liposomes suggestive of a decrease in clearance of dying cells. In sham-injured animals, microglia repopulated the clodrosome-mediated depleted brain regions over a period of 2–4 weeks and exhibited morphology typical of a resting phenotype. In brain-injured animals, the repopulated microglia in clodrosome-injected animals exhibited rod-like and amoeboid morphologies. However, fluoro-Jade B reactivity in these brain regions was more extensive than in empty liposome-injected animals suggesting that the active microglia may be unable to clear dying neurons. This was accompanied by an induction of hyperexcitability in the local cortical circuitry. Depletion of microglia within the white matter tracts and the thalamus did not affect the extent of injury-induced traumatic axonal injury. Increased neurodegeneration in the dorsal subiculum was not accompanied by any changes to injury-induced deficits in spatial learning and memory. These data suggest that activation of microglia may be important for removal of dying neurons in the traumatically-injured immature brain. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00144886
Volume :
316
Database :
Academic Search Index
Journal :
Experimental Neurology
Publication Type :
Academic Journal
Accession number :
136133035
Full Text :
https://doi.org/10.1016/j.expneurol.2019.04.004