1. Long-term cognitive deficits after traumatic brain injury associated with microglia activation
- Author
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Esber S. Saba, Hala Darwish, Firas Kobeissy, Mona Karout, Samia J. Khoury, and Leila Nasrallah
- Subjects
Male ,Traumatic brain injury ,Models, Neurological ,Immunology ,Central nervous system ,Spatial Learning ,Brain tissue ,Models, Psychological ,Translational Research, Biomedical ,Mice ,Spatio-Temporal Analysis ,Brain Injuries, Traumatic ,Animals ,Immunology and Allergy ,Medicine ,Cognitive Dysfunction ,Maze Learning ,Spatial Memory ,Microglia ,business.industry ,Brain ,Cognition ,Flow Cytometry ,medicine.disease ,Phenotype ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,Nonlinear Dynamics ,nervous system ,Spatial learning ,business ,Neuroscience ,Homeostasis - Abstract
Background: Traumatic Brain Injury (TBI) is the most prevalent of all head injuries, and based on the severity of the injury, it may result in chronic neurologic and cognitive deficits. Microglia play an essential role in homeostasis and diseases of the central nervous system. We hypothesize that microglia may play a beneficial or detrimental role in TBI depending on their state of activation and duration.Methods: In the present study, we evaluated whether TBI results in a spatiotemporal change in microglia phenotype and whether it affects sensory-motor or learning and memory functions in male C57BL/6 mice. We used a panel of neurological and behavioral tests and a multi-color flow cytometry-based data analysis followed by unsupervised clustering to evaluate isolated microglia from injured brain tissue. Results: We characterized several microglial phenotypes and their association with cognitive deficits. TBI results in a spatiotemporal increase in highly activated microglia that correlated negatively with spatial learning and memory at 35 days post-injury.Conclusions: These observations could define therapeutic windows and accelerate translational research to improve patient outcomes.
- Published
- 2021