Neuroinflammation

Neuroinflammation

 

Principal investigator: Eduardo Molina Holgado, Ph.D.

E-mail: eduardom@sescam.jccm.es

 

 

The Laboratory of Neuroinflammation was established in 2003 to develop therapeutic strategies for pathological processes occurring after spinal cord injury. The group is composed by five senior investigators leading the research lines described below.

 

 

 

 

Scientific staff

 

Eduardo Molina-Holgado (PhD, University of Montreal, Canada 1994)

 

Angel Arevalo-Martin (PhD, Complutense University of Madrid 2003)

 

Daniel Garcia-Ovejero (PhD, Complutense University of Madrid 2004)

 

Rafael Moreno-Luna (PhD, University of Cordoba 2007)

 

Pedro F. Esteban (PhD, University of Salamanca 1996)

 

Beatriz Paniagua-Torija (BSc, University of Castilla-La Mancha 2017)

 

Maria del Mar del Cerro Mayo (Technician)

 

 

 

 

Research lines

 

- Role of autoantibodies in spinal cord injury pathogeny (Angel Arevalo-Martin / Daniel Garcia-Ovejero)

 

Autoantibodies against central nervous system increase after spinal cord injury and are related, in experimental models, with neurological damage. Our group has identified 13 novel autoantibodies in patients at the acute/subacute phase that have their origin in natural antibodies. Currently, we are studying whether one of these autoantibodies related to poor neurological recovery is, besides a prognostic biomarker, a pathogenic factor.

 

Collaborators:
Dr. Lukas Grassner (University of British Columbia, Vancouver, Canada; Paracelsus Medical University, Salzburg, Austria)
Dr. Doris Maier and Orpheus Mach (Center for Spinal Cord Injuries, Trauma Center, Murnau, Germany)

 

 

- Biomarkers in spinal cord injury (Angel Arevalo-Martin / Daniel Garcia-Ovejero)

 

Besides discovering new potential therapeutic targets, identifying biomarkers that accurately predict neurological recovery would be helpful for developing personalized rehabilitation therapies and estimating the expected recovery of untreated acute patients in clinical trials. To achieve this, first we have developed in the context of an international collaboration a score of change in the neurological function –INCS, from “Integrated Neurological Change Score”– that follows the clinical judgement about the meaningfulness of neurological recovery and is highly sensitive. Currently we are studying biomarkers of neurological function change (INCS) as well as of secondary complications, like enhanced susceptibility to infections.

 

Collaborators:
Dr. Lukas Grassner (University of British Columbia, Vancouver, Canada; Paracelsus Medical University, Salzburg, Austria)
Dr. Doris Maier, Orpheus Mach and Dr. Iris Leister (Center for Spinal Cord Injuries, Trauma Center, Murnau, Germany)
Dr. John K Kramer (University of British Columbia, Vancouver, Canada)
Dr. Ludwig Aigner (Paracelsus Medical University, Salzburg, Austria)

 

 

- Ependymal region, spinal cord repair and ependymomas (Daniel Garcia-Ovejero)

 

In vertebrate species that spontaneously regenerate the damaged spinal cord, the ependymal region plays a crucial role. In the last years, we have reported relevant contributions to this field, describing similarities and differences between the human ependymal region and that from other species, showing that the structure and molecular profile of this region are a unique human trait.  We are currently exploring the relationship between the ependymal region and the appearance of ependymal tumours (ependymomas), and the possible role of human endogenous retroviruses (HERVs) in this process. Our goal is to find therapeutical tools since ependymomas have no current effective treatments beyond surgery.

 

Collaborators:
Dr. Isidro Ferrer (IDIBELL, Barcelona, Spain)
GeNeuro (Geneva, Suiza)

 

 

- Cannabinoid receptor CB1 and endocannabinoids in oligodendrocyte development (Eduardo Molina-Holgado)

 

Endocannabinoids are a family of lipidic messengers synthesized from phospholipid precursors in the plasma membrane in response to cellular activation. Our results show the expression of CB1 and CB2 receptors in oligodendrocyte cultures, in the postnatal and adult rat corpus callosum and in the white matter of the spinal cord. Oligodendrocytes and  oligodendrocyte precursor cells (OPCs) express a full endocannabinoid signaling machinery necessary to maintain their proliferation, differentiation and migration. Nevertheless, the role of the endocannabinoid 2-AG produced in situ by the oligodendrocyte in myelination during CNS development or after a demyelinating lesion is yet to be determined and constitute our objective.

 

 

- Anosmin 1 mechanism of action (Pedro F. Esteban)

 

My research interest is focused on the mechanism of action of the protein anosmin 1, involved in Kallmann syndrome etiology. We study the molecular interactions of anosmin 1 and how these interactions modulate the activity of the different membrane receptors with which it interacts. Currently we are studying the interaction of anosmin 1 and the prokineticin receptor 2 and how this interaction modulates this receptor activity, involved in inflammation, pain or cancer.

 

 

- Cell-based therapy for regenerative medicine (Rafael Moreno-Luna)

 

My main line of work focuses on the study of the potential therapeutic use of vascular stem and progenitor cells that participate in the formation of the vascular bed, for their subsequently use in tissue repair and/or regeneration. We are currently conducting a preclinical study, funded by the ISCIII (Ref: PI18700427 (2019-2023) and co-financed by European funds, whose main objective is focused on establishing the criteria to make the use of autologous cells viable and safe for the repair and/or reconstruction of pressure ulcers in patients with spinal cord injury. Additionally, we are collaborating with different institutions in the development of therapeutic strategies based on these same cells, but in different pathophysiologies. In 2020 we started a line of research focused on the implications that the COVID-19 infection could have on our different approaches. In 2021 we joined the RICORS research group on cerebral vascular diseases (stroke), in the consortium of biomedical research centers (CIBER), exp: RD21/0006/0002.

 

 

 

 

Selected publications since 2015

 

- Grassner L, Garcia-Ovejero D, Mach O, Lopez-Dolado E, Vargas-Vaquero E, Alcobendas M, Esclarin A, Sanktjohanser L, Wutte C, Becker J, Lener S, Hartmann S, Girod PP, Koegl N, Griessenauer C, Papadopoulos MC, Geisler F, Thomé C, Molina-Holgado E, Vidal J, Curt A, Scivoletto G, Guest J, Maier D, Weidner N, Rupp R, Kramer JLK, Arevalo-Martin A. A new score based on the international standards for neurological classification of spinal cord injury for integrative evaluation of changes in sensorimotor functions. J Neurotrauma. 2021 Dec 23. doi: 10.1089/neu.2021.0368.

 

- Molina-Holgado E, Esteban PF, Arevalo-Martin A, Moreno-Luna R, Molina-Holgado F, Garcia-Ovejero D. (2022) Endocannabinoid signaling in oligodendroglia. GLIA, in press

 

- Torrillas de la Cal A, Paniagua-Torija B, Arevalo-Martin A, Faulkes CG, Jiménez AJ, Ferrer I, Molina-Holgado E, Garcia-Ovejero D. (2021) The Structure of the Spinal Cord Ependymal Region in Adult Humans Is a Distinctive Trait among Mammals. Cells 10(9):2235. doi: 10.3390/cells10092235.

 

- Molina-Holgado E, Paniagua-Torija B, Arevalo-Martin A, Moreno-Luna R, Esteban PF, Le MQU, Del Cerro MDM, Garcia-Ovejero D. (2021) Cannabinoid Receptor 1 associates to different molecular complexes during GABAergic neuron maturation. J Neurochem. 58(3):640-656. doi: 10.1111/jnc.15381

 

- Moreno-Luna R, Esteban PF, Paniagua-Torija B, Arevalo-Martin A, Garcia-Ovejero D, Molina-Holgado E. (2021) Heterogeneity of the Endocannabinoid System Between Cerebral Cortex and Spinal Cord Oligodendrocytes. Mol Neurobiol. 58(2):689-702. doi: 10.1007/s12035-020-02148-1

 

- Esteban PF, Garcia-Ovejero D, Paniagua-Torija B, Moreno-Luna R, Arredondo LF, Zimmer A, Arévalo-Martín A, Molina-Holgado E. (2020) Revisiting CB1 cannabinoid receptor detection and the exploration of its interacting partners. J Neurosci Methods 337:108680 doi: 10.1016/j.jneumeth.108680.

 

- Beltran-Camacho L, Jimenez-Palomares M, Rojas-Torres M, Sanchez-Gomar I, Rosal-Vela A, Eslava-Alcon S, Perez-Segura MC, Serrano A, Antequera-González B, Alonso-Piñero JA, González-Rovira A, Extremera-García MJ, Rodriguez-Piñero M, Moreno-Luna R, Larsen MR, Durán-Ruiz MC. (2020) Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia. Stem Cell Res Ther. 11(1):106. doi: 10.1186/s13287-020-01591-0.

 

- Eslava-Alcon S, Extremera-García MJ, Sanchez-Gomar I, Beltrán-Camacho L, Rosal-Vela A, Muñoz J, Ibarz N, Alonso-Piñero JA, Rojas-Torres M, Jiménez-Palomares M, González-Rovira A, Conejero R, Doiz E, Rodriguez-Piñero M, Moreno-Luna R, Durán-Ruiz MC. (2020) Atherosclerotic Pre-Conditioning Affects the Paracrine Role of Circulating Angiogenic Cells Ex-Vivo. Int J Mol Sci. 21(15):5256. doi: 10.3390/ijms21155256.

 

- Arevalo-Martin A, Grassner L,  Garcia-Ovejero D,  Paniagua-Torija B,  Barroso-Garcia G, Gonzalez Arandilla A,  Mach O,  Turrero A,  Vargas E,  Alcobendas M,  Rosell C, Alcaraz MA,  Ceruelo S,  Casado R,  Talavera F,  Palazon R,  Sanchez-Blanco N,  Maier D, Esclarin A and  Molina-Holgado E. (2018). Elevated autoantibodies in subacute human spinal cord injury are naturally occurring antibodies. Front. Immunol. 9:2365 doi: 10.3389/fimmu.2018.02365.

 

- Paniagua-Torija B, Norenberg M, Arevalo-Martin A, Carballosa-Gautam MM, Campos-Martin Y, Molina-Holgado E, Garcia-Ovejero D. (2018). Cells in the adult human spinal cord ependymal region do not proliferate after injury. J Pathol. 246 (4): 415- 421.

 

- Garcia-Ovejero D, Arevalo-Martin A, Paniagua-Torija B, Florensa-Vila J, Ferrer I, Grassner L, Molina-Holgado E. (2015) The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features. Brain 138 (Pt 6):1583-97.