Neuroinflammation Mediated by Glia Maturation Factor Exacerbates Neuronal Injury in an in vitro Model of Traumatic Brain Injury
Open accessAbstract
Traumatic brain injury (TBI) is the primary cause of death and disability affecting over 10 million people in the industrialized world. TBI causes a wide spectrum of secondary molecular and cellular complications in the brain. However, the pathological events are still not yet fully understood. Previously, we have shown that the glia maturation factor (GMF) is a mediator of neuroinflammation in neurodegenerative diseases. To identify the potential molecular pathways accompanying TBI, we used an in vitro cell culture model of TBI. A standardized injury was induced by scalpel cut through a mixed primary cell culture of astrocytes, microglia and neurons obtained from both wild type (WT) and GMF-deficient (GMF-KO) mice. Cell culture medium and whole–cell lysates were collected at 24, 48, and 72 h after the scalpel cuts injury and probed for oxidative stress using immunofluorescence analysis. Results showed that oxidative stress markers such as glutathione and glutathione peroxidase were significantly reduced, while release of cytosolic enzyme lactate dehydrogenase along with nitric oxide and prostaglandin E2 were significantly increased in injured WT cells compared with injured GMF-KO cells. In addition, injured WT cells showed increased levels of oxidation product 4-hydroxynonenal and 8-oxo-2′-deoxyguanosine compared with injured GMF-KO cells. Further, we found that injured WT cells showed a significantly increased expression of glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and phosphorylated ezrin/radixin/moesin proteins, and reduced microtubule associated protein expression compared with injured GMF-KO cells after injury. Collectively, our results demonstrate that GMF exacerbates the oxidative stress–mediated neuroinflammation that could be brought about by TBI-induced astroglial activation.
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Activation of MSN in association with ezrin and radixin has been implicated in the neuroprotective non-amyloidogenic processing of APP.
“Its activation in association with proteins ezrin and radixin has been implicated in the neuroprotective non-amyloidogenic processing of APP [123, 124].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [124]
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- Authors
- Ahmed, M. E., Selvakumar, G. P., Kempuraj, D., Raikwar, S. P., Thangavel, R., Bazley, K., Wu, K., Khan, O., Kukulka, K., Bussinger, B., Dubova, I., Zaheer, S., Govindarajan, R., Iyer, S., Burton, C., James, D., & Zaheer, A.
- Affiliations
- Harry S. Truman Memorial Veterans' Hospital (US)
- University of Missouri (US)
- Phelps County Regional Medical Center (US)
- Corresponding author
- Zaheer, Asgar
- ORCID
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2020-07-15
- Volume
- 37
- Issue
- 14
- Pages
- 1645-1655
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- PMC
- PMC7336883
- OpenAlex
- W3012777316
- Cited by
- 13
- References
- 43
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 3 · 2020: 5
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- traumatic brain injury, neuroinflammation, oxidative stress, astroglial activation, neuronal injury, glutathione, 4-hydroxynonenal, 8-hydroxy-2'-deoxyguanosine, nitric oxide, prostaglandin E2, ezrin/radixin/moesin, glial fibrillary acidic protein, microtubule-associated proteins, astrocytes, microglia
- MeSH terms
- Brain Injuries, Traumatic, Animals, Astrocytes, Cell Movement, Cells, Cultured, Mice, Inbred C57BL, Neurons, Microglia, Mice, Knockout, Oxidative Stress, Inflammation Mediators, Glia Maturation Factor, Mice
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