The expression of repulsive guidance molecule a after traumatic brain injury: Time-course changes in gene expression in a murine model of controlled cortical impact
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Updated: Nov 27, 2025
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Eri Uemura1, Goro Tajima, Shimon Murahashi
1From the Department of Emergency Medicine (E.U., S.M., N.M., O.T.), Nagasaki University Graduate School of Biomedical Sciences; Acute and Critical Care Center (E.U., G.T., S.M., N.M., A.T., M.M., O.T.), Nagasaki University Hospital; and Department of Forensic Pathology and Science (T.M., K.I.), Nagasaki University Graduate School of Biomedical Sciences Nagasaki, Japan.
Introduction:
Repulsive guidance molecule a (RGMa) is a key protein that negatively regulates neuronal regeneration as its inhibition enhances axonal growth and promotes functional recovery in animal models of spinal cord injury. However, the role of RGMa in traumatic brain injury (TBI) remains elusive. This study aimed to clarify TBI-responsive RGMa expression in a murine model.
Methods:
Adult male C57BL/6J mice were subjected to controlled cortical impact. Brains were extracted 6 hours and 1, 3, 7, 14 and 21 days after injury (n = 6 in each group). Changes in the messenger RNA (mRNA) expression of RGMa and its receptor, neogenin, were evaluated by quantitative polymerase chain reaction in the damaged area of the cortex and contralateral cortex, along with expression measurement of inflammation-related molecules. Neurological deficit was also assessed by the cylinder test.
Results:
Neurological score was consistently lower in the TBI group compared to the sham group throughout the experimental period. The mRNA expressions of representative inflammatory cytokine TNF-α and chemokine receptor CCR2 were remarkably increased in the injured cortex on day 1 and gradually decreased over time, although remaining at higher values at least until day 14. The mRNA expressions of RGMa and neogenin were significantly suppressed in the damaged cortex until day 3. Interestingly, RGMa expression was suppressed most on day 1 and recovered over time.
Conclusion:
In the acute phase of TBI, gene expression of inflammatory cytokines significantly increased, and gene expressions of RGMa and neogenin significantly decreased in the inflammatory milieu of the damaged area. Despite the subsequent remission of inflammation, RGMa gene expression recovered to the normal level 1 week after TBI. Intrinsic regenerative response to acute brain injury might be hampered by the following recovery of RGMa expression, hinting at the possibility of functional RGMa inhibition as a new, effective maneuver against TBI.
