Neuroinflammatory responses after experimental diffuse traumatic brain injury.
Little is known about microglial activation and macrophage localization after diffuse brain injury (DBI). DBI-mediated perisomatic traumatic axonal injury (TAI) was recently identified within the neocortex, hippocampus, and thalamus, providing an opportunity to characterize immune cell responses within diffusely injured brain loci uncomplicated by contusion. By using moderate midline/central fluid percussion injury, microglial/macrophage responses were examined with antibodies targeting immune cell phenotypes and amyloid precursor protein, a marker of TAI. Parallel assessments of blood-brain barrier alterations were also performed. Within 6 to 48 hours postinjury, microglial activation within injured loci was observed, whereas microglia within non-TAI-containing regions maintained a resting phenotype. Microglial activation shared a spatiotemporal relationship with TAI though no clear interactions were observed. By 7 to 28 days postinjury, activated microglia contained myelin debris, yet revealed limited aggregation. Immunophenotypic macrophages were also localized to injured loci. Select macrophages approximated somatic membranes of perisomatically axotomized neurons with evidence of bouton disruption. No causality was established between blood-brain barrier alterations and these inflammatory responses. These findings indicate rapid, yet initially nonspecific, and persistent microglial/macrophage responses to DBI. DBI-mediated inflammatory responses suggest further expansion of traumatic brain injury histopathologic evaluations to identify neuroinflammation indicative of diffuse pathology.
Kelley
Brian Joseph
BJ
Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0709, USA.
Lifshitz
Jonathan
J
Povlishock
John Theodore
JT
D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology; D001930:Brain Injuries / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D017628:Microglia / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley