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.
Journal
The journal of trauma and acute care surgery
ISSN: 2163-0763
Titre abrégé: J Trauma Acute Care Surg
Pays: United States
ID NLM: 101570622
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
pubmed:
3
12
2020
medline:
16
4
2021
entrez:
2
12
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 33264266
pii: 01586154-202102000-00010
doi: 10.1097/TA.0000000000003041
doi:
Substances chimiques
Ccr2 protein, mouse
0
GPI-Linked Proteins
0
Nerve Tissue Proteins
0
Receptors, CCR2
0
Rgma protein, mouse
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
281-286Informations de copyright
Copyright © 2020 American Association for the Surgery of Trauma.
Références
Menon DK, Schwab K, Wright DW, Maas AI; Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health. Position statement: definition of traumatic brain injury. Arch Phys Med Rehabil . 2010;91(11):1637–1640.
Dewan MC, Rattani A, Gupta S, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg . 2018;1–18.
Alarcon JD, Rubiano AM, Okonkwo DO, Alarcón J, Martinez-Zapata MJ, Urrutia G, Bonfill Cosp X. Elevation of the head during intensive care management in people with severe traumatic brain injury. Cochrane Database Syst Rev . 2017;12:CD009986.
Stahl B, Müller B, von Boxberg Y, Cox EC, Bonhoeffer F. Biochemical characterization of a putative axonal guidance molecule of the chick visual system. Neuron . 1990;5(5):735–743.
Müller BK, Jay DG, Bonhoeffer F. Chromophore-assisted laser inactivation of a repulsive axonal guidance molecule. Curr Biol . 1996;6(11):1497–1502.
Monnier PP, Sierra A, Macchi P, et al. RGM is a repulsive guidance molecule for retinal axons. Nature . 2002;419(6905):392–395.
Niederkofler V, Salie R, Sigrist M, Arber S. Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system. J Neurosci . 2004;24(4):808–818.
Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, Mueller BK, Strittmatter SM. Neogenin mediates the action of repulsive guidance molecule. Nat Cell Biol . 2004;6(8):756–762.
Yamashita T, Mueller BK, Hata K. Neogenin and repulsive guidance molecule signaling in the central nervous system. Curr Opin Neurobiol . 2007;17(1):29–34.
Chen J, Shifman MI. Inhibition of neogenin promotes neuronal survival and improved behavior recovery after spinal cord injury. Neuroscience . 2019;408:430–447.
Siebold C, Yamashita T, Monnier PP, Mueller BK, Pasterkamp RJ. RGMs: structural insights, molecular regulation, and downstream signaling. Trends Cell Biol . 2017;27(5):365–378.
Muramatsu R, Kubo T, Mori M, et al. RGMa modulates T cell responses and is involved in autoimmune encephalomyelitis. Nat Med . 2011;17(4):488–494.
Demicheva E, Cui YF, Bardwell P, et al. Targeting repulsive guidance molecule A to promote regeneration and neuroprotection in multiple sclerosis. Cell Rep . 2015;10(11):1887–1898.
Schwab JM, Conrad S, Monnier PP, Julien S, Mueller BK, Schluesener HJ. Spinal cord injury-induced lesional expression of the repulsive guidance molecule (RGM). Eur J Neurosci . 2005;21(6):1569–1576.
Hata K, Fujitani M, Yasuda Y, Doya H, Saito T, Yamagishi S, Mueller BK, Yamashita T. RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J Cell Biol . 2006;173(1):47–58.
Nakagawa H, Ninomiya T, Yamashita T, Takada M. Treatment with the neutralizing antibody against repulsive guidance molecule-a promotes recovery from impaired manual dexterity in a primate model of spinal cord injury. Cereb Cortex . 2019;29(2):561–572.
Arevalo MA, Santos-Galindo M, Bellini MJ, Azcoitia I, Garcia-Segura LM. Actions of estrogens on glial cells: implications for neuroprotection. Biochim Biophys Acta . 2010;1800(10):1106–1112.
Kawai S, Takagi Y, Kaneko S, Kurosawa T. Effect of three types of mixed anesthetic agents alternate to ketamine in mice. Exp Anim . 2011;60(5):481–487.
Omoto S, Ueno M, Mochio S, Takai T, Yamashita T. Genetic deletion of paired immunoglobulin-like receptor B does not promote axonal plasticity or functional recovery after traumatic brain injury. J Neurosci . 2010;30(39):13045–13052.
Ueno M, Yamashita T. Kinematic analyses reveal impaired locomotion following injury of the motor cortex in mice. Exp Neurol . 2011;230(2):280–290.
Clausen F, Hanell A, Bjork M, Hillered L, Mir AK, Gram H, Marklund N. Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice. Eur J Neurosci . 2009;30(3):385–396.
Zhu W, Gao Y, Wan J, et al. Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse. Brain Behav Immun . 2018;69:568–581.
Schwab JM, Monnier PP, Schluesener HJ, Conrad S, Beschorner R, Chen L, Meyermann R, Mueller BK. Central nervous system injury-induced repulsive guidance molecule expression in the adult human brain. Arch Neurol . 2005;62(10):1561–1568.
Mothe AJ, Tassew NG, Shabanzadeh AP, et al. RGMa inhibition with human monoclonal antibodies promotes regeneration, plasticity and repair, and attenuates neuropathic pain after spinal cord injury. Sci Rep . 2017;7(1):10529.
Shabanzadeh AP, Tassew NG, Szydlowska K, et al. Uncoupling Neogenin association with lipid rafts promotes neuronal survival and functional recovery after stroke. Cell Death Dis . 2015;6:e1744.
Mirakaj V, Brown S, Laucher S, et al. Repulsive guidance molecule-A (RGM-A) inhibits leukocyte migration and mitigates inflammation. Proc Natl Acad Sci U S A . 2011;108(16):6555–6560.
Hsieh CL, Niemi EC, Wang SH, et al. CCR2 deficiency impairs macrophage infiltration and improves cognitive function after traumatic brain injury. J Neurotrauma . 2014;31(20):1677–1688.
Morganti JM, Jopson TD, Liu S, Riparip LK, Guandique CK, Gupta N, Ferguson AR, Rosi S. CCR2 antagonism alters brain macrophage polarization and ameliorates cognitive dysfunction induced by traumatic brain injury. J Neurosci . 2015;35(2):748–760.
Jin X, Ishii H, Bai Z, Itokazu T, Yamashita T. Temporal changes in cell marker expression and cellular infiltration in a controlled cortical impact model in adult male C57BL/6 mice. PloS One . 2012;7(7):e41892.
Nguyen HX, Beck KD, Anderson AJ. Quantitative assessment of immune cells in the injured spinal cord tissue by flow cytometry: a novel use for a cell purification method. J Vis Exp . 2011;(50):2698.
Semple BD, Bye N, Rancan M, Ziebell JM, Morganti-Kossmann MC. Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2−/− mice. J Cereb Blood Flow Metab . 2010;30(4):769–782.
Tanaka T, Ueno M, Yamashita T. Engulfment of axon debris by microglia requires p38 MAPK activity. J Biol Chem . 2009;284(32):21626–21636.
Jin X, Yamashita T. Microglia in central nervous system repair after injury. J Biochem . 2016;159(5):491–496.
Verma S, Nakaoke R, Dohgu S, Banks WA. Release of cytokines by brain endothelial cells: a polarized response to lipopolysaccharide. Brain Behav Immun . 2006;20(5):449–455.
Hu X, Li P, Guo Y, Wang H, Leak RK, Chen S, Gao Y, Chen J. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke . 2012;43(11):3063–3070.
Roughton K, Andreasson U, Blomgren K, Kalm M. Lipopolysaccharide-induced inflammation aggravates irradiation-induced injury to the young mouse brain. Dev Neurosci . 2013;35(5):406–415.
Kitayama M, Ueno M, Itakura T, Yamashita T. Activated microglia inhibit axonal growth through RGMa. PloS One . 2011;6(9):e25234.
Fraunberger EA, DeJesus P, Zanier ER, Shutt TE, Esser MJ. Acute and persistent alterations of cerebellar inflammatory networks and glial activation in a rat model of pediatric mild traumatic brain injury. J Neurotrauma . 2020;37(11):1315–1330.