Retina microglial activation and functional deficits in an impact concussion mouse model.of traumatic brain injury (TBI).

Abstract

Purpose : Traumatic Brain Injury (TBI) induces brain inflammation characterized by reactive microgliosis, infiltration of peripheral monocytes, and pro- and anti-inflammatory molecules. These responses can either facilitate recovery or trigger sequelae. Activation and interaction of specific immune cells and phenotypes are determinative of temporal pacing and outcome of brain recovery after concussive head injury.

Methods : We utilized Ccr2RFP/Cx3cr1GFP mice (Jackson Laboratory) to enable immune cell visualization by class (microglia, monocyte), origin (peripheral, brain, retina), morphology, and location. We used a closed-head impact injury mouse model that recapitulates key features of human concussion. Experimental injury was conducted without anesthesia (approved IACUC protocol) to enable quantitative neurological assessment (Boston University Concussion Scale, BUCS). We evaluated histopathology, ultrastructural analysis, bloodbrain/retinal barrier function, immune cell imaging, and electrophysiology. We also used an adaptive optics fluorescence scanning laser ophthalmoscope (AO-fSLO) with OCT imaging (Physical Sciences, Inc.).

Results : Head-injured mice exhibited transient contralateral hemiparesis, truncal ataxia, impaired balance, and abnormal locomotion that recapitulated concussion in humans. We observed significant increase in microglia in retina and brain post-injury. Impact injury induced axonopathy, blood-brain barrier disruption, reactive astrocytosis and microgliosis, and peripheral monocyte infiltration in brain and retina.

Conclusions : Closed-head impact injury is associated with reactive inflammatory responses and sequelae in both retina and brain. The retina can be used as a “brain proxy” for noninvasive diagnosis, prognosis, staging and monitoring of neuroinflammation after closed-head injuries.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.