Neuroregeneration and innate immunity
Neuroregeneration and innate immunity
The research group Neuroregeneration and Innate Immuniy (LRNI) was established in 2016 in the new research building of the hospital. We are investigating the molecular mechanisms of neuroinflammation and phagocytosis after CNS lesions. Our research focuses on the signaling pathways of bile acids and retinoids. The laboratory works with molecular biology and biochemistry methods, uses animal models such as spinal cord contusion injury in rats and primary cell cultures of microglia, macrophages and neurons. We are searching for new therapies of spinal cord injury. A clinical trial is being prepared in cooperation with an industrial partner.
The group has three lines of fundamental and translational research:
1.- Functions and molecular mechanisms of the bile acid receptor TGR5 and RXR related nuclear receptors in the central nervous system
2.- Regulation of phagocytosis by macrophages and microglia in neuropathologies
3.- Bone marrow-derived stem cells as treatment of spinal cord injury
Academic teaching has always been an important part of our activity. We offer MSc and BSc thesis projects in cooperation with the University of Castilla-la Mancha and the Universidad Autónoma de Madrid. The prinicipal investigator is adjunct professor of RWTH Aachen University, Germany and member of the executive board of EURON, an international graduate school of neuroscience, located in Maastricht, Netherlands [http://www.euronschool.eu/].
- N. Yanguas-Casás, A. Ojalvo-Sanz, A. Martínez-Vázquez, M.-F. Goneau, M. Gilbert, M. Nieto-Sampedro, L. Romero-Ramírez. Neurostatin and other O-acetylated gangliosides show anti-neuroinflammatory activity involving the NFκB pathway. Toxicol. Appl. Pharmacol. (2019) in press.
- N. Yanguas-Casás, M.A. Barreda-Manso, M. Nieto-Sampedro, L. Romero-Ramírez. TUDCA: An antagonist of the bile acid receptor GPBAR1/TGR5 with antiinflammatory effects in microglial cells. J. Cell. Physiol. 232 (2017): 2231-2245.
- N. Yanguas-Casás, M.A. Barreda-Manso, S. Pérez-Rial, M. Nieto-Sampedro, L. Romero-Ramírez. TGFβ contributes to the anti-inflammatory effect of tauroursodeoxycholic acid on an animal model of neuroinflammation. Mol. Neurobiol. 54 (2017): 6737-6749.
- S. van Neerven, T. Regen, D. Wolf, A. Nemes, S. Johann, C. Beyer, U.-K. Hanisch and J. Mey. Inflammatory chemokine release of astrocytes in vitro is reduced by all-trans retinoic acid. J. Neurochem. 114 (2010): 1511-1526.
- S. van Neerven, A. Nemes, P. Imholz, T. Regen, B. Denecke, S. Johann, C. Beyer, U.-K. Hanisch and J. Mey. Inflammatory cytokine release of astrocytes in vitro is reduced by all-trans retinoic acid. J. Neuroimmunol. 229 (2010): 169-179.
Spinal cord injury:
- D. Fandel, D. Wasmuht, G. Ávila-Martín, J. S. Taylor, I. Galán-Arriero, J. Mey. Spinal cord injury induced changes of nuclear receptors PPARα and LXRβ and modulation with oleic acid/albumin treatment. Brain Res. 1535 (2013): 89-105.
- G.C. Koopmans, R. Deumens, W. Honig, F.P.T. Hamers, J. Mey, M. van Kleef and E.A.J. Joosten. Functional recovery, serotonergic sprouting and endogenous progenitor fates in response to delayed environmental enrichment after spinal cord injury. J. Neurotrauma 29 (2012): 514-527.
- S. van Neerven, J. Mey, E. A. Joosten, H. W. Steinbusch, M. van Kleef, A. Marcus and R. Deumens. Systemic but not local administration of retinoic acid reduces early transcript levels of pro-inflammatory cytokines after experimental spinal cord injury. Neurosci. Lett. 485 (2010): 21-25.
- S. van Neerven, E. A. Joosten, G. A. Brook, C. A. Lambert, J. Mey, J. Weis, M. A. Marcus, H. W. Steinbusch, M. van Kleef, J. Patijn and R. Deumens. Repetitive intrathecal VEGF165 treatment has limited therapeutic effects after spinal cord injury in the rat. J. Neurotrauma 27 (2010): 1781-1791.
- J. Mey, D. Morassutti, G. Brook, R.-H. Liu, Y.-P.Zhang, G. Koopmans and P. McCaffery. Retinoic acid synthesis by a population of NG-positive cells in the injured spinal cord. Eur. J. Neurosci. 21 (2005): 1555-1568.
- H. Groult, I. García-Álvarez, L. Romero-Ramírez, M. Nieto-Sampedro, F. Herranz, A. Fernández-Mayoralas, J. Ruiz-Cabello. Micellar iron oxide nanoparticles coated with anti-tumor glycosides. Nanomaterials 8 (2018): E567.
- A. Kriebel, D. Hodde, T. Künzel, J. Engels, G. Brook, J. Mey. Cell-free artificial implants of electrospun fibres in a three-dimensional gelatin matrix support sciatic nerve regeneration in vivo. J. Tiss. Eng. Reg. Med. 11 (2017): 3289-3304.
- A. Kriebel, M. Rumman, M. Scheld, D. Hodde, G. Brook, J. Mey. Three-dimensional configuration of orientated fibers as guidance structures for cell migration and axonal groath. J. Biomed. Mat. Res. B 102 (2014): 356-365.
- J. Bockelmann, K. Klinkhammer, N. Seiler, A. von Holst, G. A. Brook, A. Faissner, D. Klee, J. Mey. Functionalization of electrospun poly(ε-caprolactone) fibers with the extracellular matrix-derived peptide GRGDS improves guidance of Schwann cell migration and axonal growth. Tiss. Eng. A, 17 (2011): 475-486.
- M.A. Barreda-Manso, N. Yanguas-Casás, M. Nieto-Sampedro, L. Romero-Ramírez. Neuroprotection and blood-brain barrier restoration by salubrinal after a cortical stab injury. J. Cell. Physiol. 232 (2017): 1501-1510.
- A.-C. Joel, A. Habedank, J. Hausen, J. Mey. Fighting for the web: intraspecific competition between female feather-legged spiders (Uloborus plumipes). Zoology 121 (2017): 10-17.
- A.-C. Joel, A. Habedank, J. Mey. Vibratory movements in contests between females of the feather-legged spider (Uloborus plumipes). Zoology 125 (2017): 87-93.
- L. Romero-Ramírez, I. García-Álvarez, J. Casas, M.A. Barreda-Manso, N. Yanguas-Casás, M. Nieto-Dampedro, A. Fernández-Mayorales. New oleyl glycoside as anti-cancer agent that targets on neutral sphingomyelinase. Biochem. Pharmacol. 97 (2015): 158-172.
- Peter McCaffery. University of Aberdeen, Escocia, UK.
- Anand Goswami. Clínica Universitaria de la RWTH Aachen, Alemania
- Johannes de Munter, Erik Ch. Wolters, Neuroplast BV, Maastricht, Países Bajos
- Michel Gilbert, Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, Canada.
Projects with external funding
In the past, members of the group received competitive funding for the investigation of retinoid signaling (German research foundation, DFG Me1261/3-1: 1997-1999, DFG Me1261/5-1: 2001-2004, DFG SFB542: 1999-2005, European Union FP5: 2004; EU FP6: 2006-2009), for the development of artificial implants and peripheral nerve regenration (IZKF Biomat 2005-2008, UE FP6: 2008-2009, DFG Me1261/11-1: 2011-2015), and for the modulation of the glial scar (Castilla-la Mancha FISCAM: 2010-2012).
1) Anti-inflammatory treatment with retinoids to enhance the therapeutic effect of bone marrow-derived stell cells after spinal cord injury.
Neuroplast/UM: 2017-2022, Chinese Scholarship Council: 2017-2020 .
2) Modulation of microglia for the therapy of spinal cord injury: TGR5 signaling and mesenchymal stem cell implants.
MINECO SAF2017-89366-R: 2018-2021.