Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt Praxis und Beruf Seltene Erkrankungen GOÄ & EBM
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Fachpsychotherapie Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende Patientenratgeber
Erweiterte Suche
Anmelden
nach oben
Neuroscience Bulletin
Erschienen in:

09.04.2024 | Original Article

Mertk Reduces Blood-Spinal Cord Barrier Permeability Through the Rhoa/Rock1/P-MLC Pathway After Spinal Cord Injury

verfasst von: Jiezhao Lin, Yuanfang Sun, Bin Xia, Yihan Wang, Changnan Xie, Jinfeng Wang, Jinwei Hu, Lixin Zhu

Erschienen in: Neuroscience Bulletin | Ausgabe 9/2024

Einloggen, um Zugang zu erhalten

Abstract

Disruption of the blood-spinal cord barrier (BSCB) is a critical event in the secondary injury following spinal cord injury (SCI). Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics. However, the specific involvement of Mertk in BSCB remains elusive. Here, we demonstrated a distinct role of Mertk in the repair of BSCB. Mertk expression is decreased in endothelial cells following SCI. Overexpression of Mertk upregulated tight junction proteins (TJs), reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis. Ultimately, this led to enhanced neural regeneration and functional recovery. Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk. These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.
Literatur
1.
Fischer I, Dulin JN, Lane MA. Transplanting neural progenitor cells to restore connectivity after spinal cord injury. Nat Rev Neurosci 2020, 21: 366–383.CrossRefPubMedPubMedCentral
2.
Lin J, Xiong Z, Gu J, Sun Z, Jiang S, Fan D. Sirtuins: Potential therapeutic targets for defense against oxidative stress in spinal cord injury. Oxid Med Cell Longev 2021, 2021: 7207692.CrossRefPubMedPubMedCentral
3.
Hu Y, Li L, Hong B, Xie Y, Li T, Feng C, et al. Epidemiological features of traumatic spinal cord injury in China: A systematic review and meta-analysis. Front Neurol 2023, 14: 1131791.CrossRefPubMedPubMedCentral
4.
Li G, Fan ZK, Gu GF, Jia ZQ, Zhang QQ, Dai JY, et al. Epidural spinal cord stimulation promotes motor functional recovery by enhancing oligodendrocyte survival and differentiation and by protecting myelin after spinal cord injury in rats. Neurosci Bull 2020, 36: 372–384.CrossRefPubMed
5.
Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 2001, 26: S2–S12.CrossRefPubMed
6.
Park CS, Lee JY, Choi HY, Yune TY. Suppression of transient receptor potential melastatin 7 by carvacrol protects against injured spinal cord by inhibiting blood-spinal cord barrier disruption. J Neurotrauma 2022, 39: 735–749.CrossRefPubMed
7.
Chio JCT, Wang J, Surendran V, Li L, Zavvarian MM, Pieczonka K, et al. Delayed administration of high dose human immunoglobulin G enhances recovery after traumatic cervical spinal cord injury by modulation of neuroinflammation and protection of the blood spinal cord barrier. Neurobiol Dis 2021, 148: 105187.CrossRefPubMed
8.
Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008, 57: 178–201.CrossRefPubMed
9.
Figley SA, Khosravi R, Legasto JM, Tseng YF, Fehlings MG. Characterization of vascular disruption and blood-spinal cord barrier permeability following traumatic spinal cord injury. J Neurotrauma 2014, 31: 541–552.CrossRefPubMedPubMedCentral
10.
Zhao R, Wu X, Bi XY, Yang H, Zhang Q. Baicalin attenuates blood-spinal cord barrier disruption and apoptosis through PI3K/Akt signaling pathway after spinal cord injury. Neural Regen Res 2022, 17: 1080–1087.CrossRefPubMed
11.
12.
13.
Du Y, Lu Z, Yang D, Wang D, Jiang L, Shen Y, et al. MerTK inhibits the activation of the NLRP3 inflammasome after subarachnoid hemorrhage by inducing autophagy. Brain Res 2021, 1766: 147525.CrossRefPubMed
14.
Shen K, Reichelt M, Kyauk RV, Ngu H, Shen YAA, Foreman O, et al. Multiple sclerosis risk gene Mertk is required for microglial activation and subsequent remyelination. Cell Rep 2021, 34: 108835.CrossRefPubMed
15.
Wu H, Zheng J, Xu S, Fang Y, Wu Y, Zeng J, et al. Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury. J Neuroinflammation 2021, 18: 2.CrossRefPubMedPubMedCentral
16.
Zhao B, Yin Q, Fei Y, Zhu J, Qiu Y, Fang W, et al. Research progress of mechanisms for tight junction damage on blood-brain barrier inflammation. Arch Physiol Biochem 2022, 128: 1579–1590.CrossRefPubMed
17.
Myers KV, Amend SR, Pienta KJ. Targeting Tyro3, Axl and MerTK (TAM receptors): Implications for macrophages in the tumor microenvironment. Mol Cancer 2019, 18: 94.CrossRefPubMedPubMedCentral
18.
Knox EG, Aburto MR, Tessier C, Nagpal J, Clarke G, O’Driscoll CM, et al. Microbial-derived metabolites induce actin cytoskeletal rearrangement and protect blood-brain barrier function. iScience 2022, 25: 105648.CrossRefPubMedPubMedCentral
19.
Salvador E, Burek M, Förster CY. Stretch and/or oxygen glucose deprivation (OGD) in an in vitro traumatic brain injury (TBI) model induces calcium alteration and inflammatory cascade. Front Cell Neurosci 2015, 9: 323.CrossRefPubMedPubMedCentral
20.
Li Y, Liu B, Zhao T, Quan X, Han Y, Cheng Y, et al. Comparative study of extracellular vesicles derived from mesenchymal stem cells and brain endothelial cells attenuating blood-brain barrier permeability via regulating Caveolin-1-dependent ZO-1 and Claudin-5 endocytosis in acute ischemic stroke. J Nanobiotechnology 2023, 21: 70.CrossRefPubMedPubMedCentral
21.
Xie C, Wang Y, Wang J, Xu Y, Liu H, Guo J, et al. Perlecan improves blood spinal cord barrier repair through the integrin β1/ROCK/MLC pathway after spinal cord injury. Mol Neurobiol 2023, 60: 51–67.CrossRefPubMed
22.
Li Y, Liu XT, Zhang PL, Li YC, Sun MR, Wang YT, et al. Hydroxysafflor yellow A blocks HIF-1 α induction of NOX2 and protects ZO-1 protein in cerebral microvascular endothelium. Antioxidants 2022, 11: 728.CrossRefPubMedPubMedCentral
23.
Qian ZY, Kong RY, Zhang S, Wang BY, Chang J, Cao J, et al. Ruxolitinib attenuates secondary injury after traumatic spinal cord injury. Neural Regen Res 2022, 17: 2029–2035.CrossRefPubMedPubMedCentral
24.
Ye LB, Yu XC, Xia QH, Yang Y, Chen DQ, Wu F, et al. Regulation of caveolin-1 and junction proteins by bFGF contributes to the integrity of blood-spinal cord barrier and functional recovery. Neurotherapeutics 2016, 13: 844–858.CrossRefPubMedPubMedCentral
25.
Goldim MPS, Della Giustina A, Petronilho F. Using Evans blue dye to determine blood-brain barrier integrity in rodents. Curr Protoc Immunol 2019, 126: e83.CrossRefPubMed
26.
Winkler L, Blasig R, Breitkreuz-Korff O, Berndt P, Dithmer S, Helms HC, et al. Tight junctions in the blood-brain barrier promote edema formation and infarct size in stroke—Ambivalent effects of sealing proteins. J Cereb Blood Flow Metab 2021, 41: 132–145.CrossRefPubMed
27.
Kaneko S, Iwanami A, Nakamura M, Kishino A, Kikuchi K, Shibata S, et al. A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nat Med 2006, 12: 1380–1389.CrossRefPubMed
28.
Ren ZW, Zhou JG, Xiong ZK, Zhu FZ, Guo XD. Effect of exosomes derived from miR-133b-modified ADSCs on the recovery of neurological function after SCI. Eur Rev Med Pharmacol Sci 2019, 23: 52–60.PubMed
29.
Martín-Cámara O, Cores Á, López-Alvarado P, Menéndez JC. Emerging targets in drug discovery against neurodegenerative diseases: Control of synapsis disfunction by the RhoA/ROCK pathway. Eur J Med Chem 2021, 225: 113742.CrossRefPubMed
30.
Lew ED, Oh J, Burrola PG, Lax I, Zagórska A, Través PG, et al. Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities. eLife 2014, 3: e03385.CrossRefPubMedPubMedCentral
31.
Cosemans JMEM, Van Kruchten R, Olieslagers S, Schurgers LJ, Verheyen FK, Munnix ICA, et al. Potentiating role of Gas6 and Tyro3, Axl and Mer (TAM) receptors in human and murine platelet activation and thrombus stabilization. J Thromb Haemost 2010, 8: 1797–1808.CrossRefPubMed
32.
Chung WS, Clarke LE, Wang GX, Stafford BK, Sher A, Chakraborty C, et al. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 2013, 504: 394–400.CrossRefPubMedPubMedCentral
33.
Jin LY, Li J, Wang KF, Xia WW, Zhu ZQ, Wang CR, et al. Blood-spinal cord barrier in spinal cord injury: A review. J Neurotrauma 2021, 38: 1203–1224.CrossRefPubMed
34.
Miner JJ, Daniels BP, Shrestha B, Proenca-Modena JL, Lew ED, Lazear HM, et al. The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity. Nat Med 2015, 21: 1464–1472.CrossRefPubMedPubMedCentral
35.
Rothlin CV, Leighton JA, Ghosh S. Tyro3, Axl, and Mertk receptor signaling in inflammatory bowel disease and colitis-associated cancer. Inflamm Bowel Dis 2014, 20: 1472–1480.CrossRefPubMed
Metadaten
Titel
Mertk Reduces Blood-Spinal Cord Barrier Permeability Through the Rhoa/Rock1/P-MLC Pathway After Spinal Cord Injury
verfasst von
Jiezhao Lin
Yuanfang Sun
Bin Xia
Yihan Wang
Changnan Xie
Jinfeng Wang
Jinwei Hu
Lixin Zhu
Publikationsdatum
09.04.2024
Verlag
Springer Nature Singapore
Erschienen in
Neuroscience Bulletin / Ausgabe 9/2024
Print ISSN: 1673-7067
Elektronische ISSN: 1995-8218
DOI
https://doi.org/10.1007/s12264-024-01199-x

Weitere Artikel der Ausgabe 9/2024

Morphological Tracing and Functional Identification of Monosynaptic Connections in the Brain: A Comprehensive Guide

  • Open Access
  • Protocol

Triggering Receptor Expressed on Myeloid Cells 2 Alleviated Sevoflurane-Induced Developmental Neurotoxicity via Microglial Pruning of Dendritic Spines in the CA1 Region of the Hippocampus

  • Original Article

STED Imaging of Vesicular Endocytosis in the Synapse

  • Protocol

Unveiling Promising Neuroimaging Biomarkers for Schizophrenia Through Clinical and Genetic Perspectives

  • Review

Quiescent Adult Neural Stem Cells: Developmental Origin and Regulatory Mechanisms

  • Open Access
  • Review

Convergent Neuroimaging and Molecular Signatures in Mild Cognitive Impairment and Alzheimer’s Disease: A Data-Driven Meta-Analysis with N = 3,118

  • Open Access
  • Original Article

Kompaktes Leitlinien-Wissen Neurologie (Link öffnet in neuem Fenster)

Mit medbee Pocketcards schnell und sicher entscheiden.
Leitlinien-Wissen kostenlos und immer griffbereit auf ihrem Desktop, Handy oder Tablet.

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Schadet Schichtarbeit dem Gehirn?

Eine große Registerstudie bestätigt, dass Schichtarbeit mit einem erhöhten Risiko für psychische und neurologische Erkrankungen einhergeht, sowie mit einer Volumenabnahme in Gehirnarealen, die für Depression, Angst und kognitive Funktionen relevant sind.

Obstruktive Schlafapnoe: Das steht abseits von CPAP auf dem Plan

Die obstruktive Schlafapnoe kann durch verschiedene Verfahren behandelt werden wie Lagetherapie und chirurgische Interventionen. Eine medikamentöse Therapie kommt zwar (noch) nicht infrage. Auf dem Pneumologie-Kongress wurden aber erste vielversprechende Ansätze präsentiert. 

Was tun, wenn pneumologische Medikamente Psyche und Blutbild verändern?

Arzneimittel für Patienten mit Mukoviszidose oder pulmonaler arterieller Hypertonie wirken offenbar nicht nur auf die Lunge. Was es in der Praxis zu beachten gilt, wurde beim Pneumologie-Kongress erläutert.

Lösten In-Ear-Kopfhörer den Lagerungsschwindel aus?

Ein 43-jähriger Patient stellt sich wegen Anfällen von Drehschwindel in der Notaufnahme vor. Diese kämen immer nur dann, wenn er zuvor Musik über Kopfhörer gehört habe. Könnte ein Zusammenhang bestehen?

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise