Glia Maturation Factor (GMF) Regulates Microglial Expression Phenotypes and the Associated Neurological Deficits in a Mouse Model of Traumatic Brain Injury

Autor: Govindhasamy Pushpavathi Selvakumar, Duraisamy Kempuraj, Kieran Bazley, Casey Burton, Asgar Zaheer, Sudhanshu P. Raikwar, Smita Zaheer, Shankar S. Iyer, Kristopher Wu, Donald James, Asher Khan, Osaid Khan, Mohammad Ejaz Ahmed, Ramasamy Thangavel
Rok vydání: 2020
Předmět:
Glia Maturation Factor
0301 basic medicine
medicine.medical_specialty
Traumatic brain injury
Neuroscience (miscellaneous)
Motor Activity
Glia maturation factor
03 medical and health sciences
Cellular and Molecular Neuroscience
Cognition
0302 clinical medicine
Western blot
Downregulation and upregulation
Internal medicine
Brain Injuries
Traumatic
medicine
Animals
Gliosis
Phosphorylation
Neuroinflammation
Mice
Knockout
Neurons
Microglia
medicine.diagnostic_test
business.industry
Macrophages
Calcium-Binding Proteins
Microfilament Proteins
Brain
Membrane Proteins
medicine.disease
Motor coordination
Mice
Inbred C57BL
Cytoskeletal Proteins
Disease Models
Animal
Oxidative Stress
Phenotype
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Neurology
Cytokines
medicine.symptom
business
Biomarkers
030217 neurology & neurosurgery
Zdroj: Molecular Neurobiology. 57:4438-4450
ISSN: 1559-1182
0893-7648
Popis: Traumatic brain injury (TBI) induces inflammatory responses through microglial activation and polarization towards a more inflammatory state that contributes to the deleterious secondary brain injury. Glia maturation factor (GMF) is a pro-inflammatory protein that is responsible for neuroinflammation following insult to the brain, such as in TBI. We hypothesized that the absence of GMF in GMF-knockout (GMF-KO) mice would regulate microglial activation state and the M1/M2 phenotypes following TBI. We used the weight drop model of TBI in C57BL/6 mice wild-type (WT) and GMF-KO mice. Immunofluorescence staining, Western blot, and ELISA assays were performed to confirm TBI-induced histopathological and neuroinflammatory changes. Behavioral analysis was done to check motor coordination ability and cognitive function. We demonstrated that the deletion of GMF in GMF-KO mice significantly limited lesion volume, attenuated neuronal loss, inhibited gliosis, and activated microglia adopted predominantly anti-inflammatory (M2) phenotypes. Using an ELISA method, we found a gradual decrease in pro-inflammatory cytokines (TNF-α and IL-6) and upregulation of anti-inflammatory cytokines (IL-4 and IL-10) in GMF-KO mice compared with WT mice, thus, promoting the transition of microglia towards a more predominantly anti-inflammatory (M2) phenotype. GMF-KO mice showed significant improvement in motor ability, memory, and cognition. Overall, our results demonstrate that GMF deficiency regulates microglial polarization, which ameliorates neuronal injury and behavioral impairments following TBI in mice and concludes that GMF is a regulator of neuroinflammation and an ideal therapeutic target for the treatment of TBI.
Databáze: OpenAIRE
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