Journal article
Rapid neuroinflammatory response localized to injured neurons after diffuse traumatic brain injury in swine
Experimental neurology, v 290
Apr 2017
PMID: 28081963
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Despite increasing appreciation of the critical role that neuroinflammatory pathways play in brain injury and neurodegeneration, little is known about acute microglial reactivity following diffuse traumatic brain injury (TBI) — the most common clinical presentation that includes all concussions. Therefore, we investigated acute microglial reactivity using a porcine model of closed-head rotational velocity/acceleration-induced TBI that closely mimics the biomechanical etiology of inertial TBI in humans. We observed rapid microglial reactivity within 15min of both mild and severe TBI. Strikingly, microglial activation was restrained to regions proximal to individual injured neurons – as denoted by trauma-induced plasma membrane disruption – which served as epicenters of acute reactivity. Single-cell quantitative analysis showed that in areas free of traumatically permeabilized neurons, microglial density and morphology were similar between sham or following mild or severe TBI. However, microglia density increased and morphology shifted to become more reactive in proximity to injured neurons. Microglial reactivity around injured neurons was exacerbated following repetitive TBI, suggesting further amplification of acute neuroinflammatory responses. These results indicate that neuronal trauma rapidly activates microglia in a highly localized manner, and suggest that activated microglia may rapidly influence neuronal stability and/or pathophysiology after diffuse TBI.
•Microglia responded to localized neuronal injury within minutes of closed-head TBI.•Rapid activation was only appreciable in regions exhibiting permeabilized neurons.•Microglia reactivity was exacerbated following repetitive TBI.•This gyrencephalic injury model closely replicates biomechanics of clinical TBI.•Acute inflammation may influence pathophysiology following concussion in humans.
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Details
- Title
- Rapid neuroinflammatory response localized to injured neurons after diffuse traumatic brain injury in swine
- Creators
- Kathryn L. Wofford - University of PennsylvaniaJames P. Harris - University of PennsylvaniaKevin D. Browne - University of PennsylvaniaDaniel P. Brown - University of PennsylvaniaMichael R. Grovola - University of PennsylvaniaConstance J. Mietus - University of PennsylvaniaJohn A. Wolf - University of PennsylvaniaJohn E. Duda - Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104, USAMary E. Putt - Hospital of the University of PennsylvaniaKara L. Spiller - Drexel UniversityD. Kacy Cullen - University of Pennsylvania
- Publication Details
- Experimental neurology, v 290
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000395368000008
- Scopus ID
- 2-s2.0-85009958058
- Other Identifier
- 991019169659004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences