Grupo de investigación neurovascular

Investigación

Las líneas de trabajo e investigación del grupo se centran en el estudio de la Unidad Neurovascular en situaciones fisiológicas (incluido el envejecimiento senil fisiológico) y patológicas, así como en la valoración de estrategias para su protección y reparación.

La disfunción de la Unidad Neurovascular predispone o agrava el desarrollo de enfermedades de alto impacto socioeconómico, como el accidente cerebrovascular agudo (ictus), enfermedades neurodegenerativas crónicas, particularmente la enfermedad de Alzheimer (EA), y la progresión tumoral.

En este sentido, investigamos sobre los mecanismos de protección y reparación de la Unidad Neurovascular, buscando moléculas apropiadas para el tratamiento de estas enfermedades de gran trascendencia clínica y epidemiológica, tanto por su prevalencia, incidencia y mortalidad, como por el grado de secuelas que generan.

Para abordar nuestros objetivos utilizamos modelos experimentales en roedores y técnicas anatómicas y de imagen (Resonancia Magnética Nuclear, RMN) así como técnicas histoquímicas, bioquímicas, biología celular y molecular y ensayos de comportamiento.

Líneas de investigación

1) Isquemia cerebral

Empleamos: un modelo murino de ligadura de la arteria cerebral media.

1. Los volúmenes del infarto por RMN
2. Marcadores que se ven alterados en el ictus isquémico utilizando técnicas de Histoquímica, Inmunohistoquímica, Bioquímica y Biología molecular.
3. La mejora mediante ensayos de conducta animal.

2) Enfermedad de Alzheimer

Empleamos:

1. Un modelo murino de la enfermedad, el doble transgénico para la proteína precursora del amiloide (APP swe) y la presenilina 1 (PSEN1 dE9) humanas.
2. Secciones procedentes de enfermos de Alzheimer.

• La variación en la carga de β-amiloide (Aβ).
• La gliosis, la inflamación y la neurodegeneración utilizando técnicas de Histoquímica, Inmunohistoquímica, Bioquímica y Biología molecular.
• La mejora mediante ensayos de conducta animal.

3) Tumores cerebrales

• Volúmenes tumorales por RMN.
• Marcadores tumorales utilizando técnicas de Histoquímica, Inmunohistoquímica, Bioquímica y Biología molecular.

Personal

Publicaciones de los últimos años  

• Emelina R. Rodríguez-Ruiz, Raquel Herrero-Labrador, Ana P. Fernández-Fernández, Julia Serrano-Masa,José A. Martínez-Montero, Daniel González-Nieto, Mayuri Hana-Vaish, Mohamed Benchekroun ,Lhassane Ismaili*, José Marco-Contelles and Ricardo Martínez-Murillo*, The Proof-of-Concept of MBA121, a Tacrine–Ferulic AcidHybrid, for Alzheimer’s  Disease Therapy. Internat. J. of Molecular Sciences, 24, 12254, 2023. https://doi.org/10.3390/ijms241512254 

• Knez, Damijan; Diez-Iriepa, Daniel); Chioua, Mourad; Gottinger, Andrea); Denic, Milica ; Chantegreil, Fabien; Nachon, Florian; Brazzolotto, Xavier); Skrzypczak-Wiercioch, Anna; Meden, Anze; Pislar, Anja; Kos, Janko); Zakelj, Simon; Stojan, Jure; Salat, Kinga; Serrano, Julia; Fernandez, Ana Patricia; Sanchez-Garcia, Aitana; Martinez-Murillo, Ricardo; Binda, Claudia; Lopez-Munoz, Francisco); Gobec, Stanislav); Marco-Contelles, Jose.  8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases. Acata Pharmaceutica Sinca, 13, 2152-2174, 2023. https://doi.org/10.1016/j.apsb.2023.01.013

• Chamorro, Beatriz; Izquierdo-Bermejo, Sara; Serrano, Julia; Hadjipavlou-Litina, Dimitra; Chioua, Mourad; Lopez-Munoz, Francisco; Marco-Contelles, Jose; Martinez-Murillo, Ricardo; Oset-Gasque, Maria Jesus, Neuroprotective and antioxidant properties of new quinolylnitrones in in vitro and in vivo cerebral ischemia models, Scientific Reports, Volume 13, Issue 1, 2023. DOI: http://dx.doi.org/10.1038/s41598-023-29929-7

• Garcia-Pena, Pablo; Ramos, Milagros; Lopez, Juan M.; Martinez-Murillo, Ricardo; de Arcas, Guillermo); Gonzalez-Nieto, Daniel), Preclinical examination of early-onset thalamic-cortical seizures after hemispheric stroke. Epilepsia, 2023. https://doi.org/10.1073/pnas.120529710

• Fernandez-Serra, R ; Martinez-Alonso, E; Alcazar, A; Chioua, M; Marco-Contelles, J; Martinez-Murillo, R; Ramos, M; Guinea, GV; Gonzalez-Nieto, D, Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations. International Journal of Molecular Sciences, 23, 7449, 2022. https://doi.org/10.3390/ijms23137449

• The use of Silica Microparticles to Improve the Efficiency of Optical Hyperthermia (OH). Casanova-Carvajal, O; Zeinoun, M; Urbano-Bojorge, AL; Bacha, F; Livi, JS; Agudo, E; Vargas, G; Ramos, M; Martinez-Murillo, R; Serrano-Olmedo, JJ. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22 (10) (2021)
  DOI: 10.3390/ijms22105091
• Reflections on cerebellar neuropathology in classical scrapie. Toledano-Díaz A, Álvarez MI, Rodríguez JJ, Badiola JJ, Monzón M, Toledano A. BIOMOLECULES Apr 28; 11(5):649 (2021) DOI: 10.3390/biom11050649
• Synthesis, antioxidant properties and neuroprotection of alpha-phenyl-tert-butylnitrone derived HomoBisNitrones in in vitro and in vivo ischemia models. Chamorro, B; Diez-Iriepa, D; Merás-Sáiz, B; Chioua, M; García-Vieira, D; Iriepa, I; Hadjipavlou-Litina, D; López-Muñoz, F; Martínez-Murillo, R; Gonzàlez-Nieto, D; Israel Fernández, I; Marco-Contelles, J; and Oset-Gasque, MJesús.  SCIENTIFIC REPORTS 10 (1), 2020. DOI: 10.1038/s41598-020-70690-y
• Biomaterials to Neuroprotect the Stroke Brain: A Large Opportunity for Narrow Time Windows. Gonzalez-Nieto, D; Fernandez-Serra, R; Perez-Rigueiro, J; Panetsos, F Martinez-Murillo, R; Guinea, GV. CELLS 9 (5) (2020). DOI: 10.3390/cells9051074
• Glial Alterations in Aging and Alzheimer’s disease: A novel basis to understand, prevent and treat the degenerative process. Toledano-Díaz A, Álvarez MI, Toledano A. OBM GERIATRICS 4 (2020). DOI: 10.21926/obm.geriatr.2002117
• Hippocampal CCR5/RANTES elevations in a rodent model of post-traumatic stress disorder: Maraviroc (a CCR5 Antagonist) increases corticosterone levels and enhances fear memory consolidation. Merino JJ, Muñetón-Gomez V, Muñetón-Gómez C, Pérez-Izquierdo MÁ, Loscertales M, Toledano A.
  BIOMOLECULES FEB 1; 10(2):212 (2020). DOI: 10.3390/biom10020212
• Synthesis, neuroprotective and antioxidant capacity of PBN-related indanonitrones. Jimenez-Almarza, A; Diez-Iriepa, D; Chioua, M; Chamorro, B; Iriepa, I; Martinez-Murillo, R; Hadjipavlou-Litina, D; Oset-Gasque, MJ and Marco-Contelles, J. May 2019 | BIOORGANIC CHEMISTRY 86, pp.445-451, 2019
  DOI: 10.1016/j.bioorg.2019.01.071
• Slowdown intracranial glioma progression by optical hyperthermia therapy: study on a CT-2A mouse astrocytoma model. Casanova-Carvajal, O; Urbano-Bojorge, AL; Ramos, M; Serrano-Olmedo, JJ; and Martinez-Murillo, R. NANOTECHNOLOGY 30 (35), 2019. DOI: 10.1088/1361-6528/ab2164
• Elevated systemic L-Kynurenine/L-Tryptophan ratio andi increased IL-1 beta and Chemokine (CX3CL1, MCP-1) proinflammatory mediators in patients with long-term titanium dental implants. Merino JJ, Cabaña Muñoz ME, Toledano A, Garcimartín A, Benedí, J, Camacho Alonso F, Parmigiani Izquierdo JM.
  J CLIN MED SEP 2; 8(9):1368 (2019). DOI: 10.3390/jcm8091368
• The long-term algae extract and aminosulphurate supplementation modulates SOD-1 activity and decrease heavymetals levels in patients with long-term dental titanium implants and amalgam fillings restorations. Merino JJ, Parmigiani Izquierdo JM, Toledano A,Cabaña Muñoz ME. ANTIOXIDANTS 2019 APR 16, 8(4):101 (2019). DOI: 10.3390/antiox8040101. 8-4
• Cortical Reshaping and Functional Recovery Induced by Silk Fibroin Hydrogels-Encapsulated Stem Cells Implanted in Stroke Animals. Fernandez-Garcia, L; Perez-Rigueiro, J; Martinez-Murillo, R ; Panetsos, F; Ramos, M; Guinea, GV; Gonzalez-Nieto, D. FRONTIERS IN CELLULAR NEUROSCIENCE 12 (2018)
  DOI: 10.3389/fncel.2018.00296
• The APPswe/PS1A246E mutations in an astrocytic cell line leads to increased vulnerability to oxygen and glucose deprivation, Ca2+ dysregulation, and mitochondrial abnormalities. Martin-de-Saavedra, MD; Navarro, E; Moreno-Ortega, AJ; Cunha, MP; Hernansanz-Agustin, P ; Leon, R; Cano-Abad, MF ; Martinez-Ruiz, A; Martinez-Murillo, R; Duchen, MR; Lopez, MG. JOURNAL OF NEUROCHEMISTRY 145 (2), pp.170-182 (2018). DOI: 10.1111/jnc.14293
• Neuron-Astrocyte Signaling is preserved in the Aging Brain. Gomez-Gonzalo, M ; Martin-Fernandez, M ; Martinez-Murillo, R ; Mederos, S ; Hernandez-Vivanco, A ; Jamison, S ;Fernandez AP ; Serrano, J ; Calero, P ; Futch, HS ; Corpas, R ; Sanfeliu, C ; Perea, G ; Araque, A. GLIA: 65 (4):569-580 (2017). DOI: 10.1002/glia.23112
• The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease. Serrano, MP ; Herrero-Labrador, R ; Futch, HS ; Serrano, J ; Romero, A ; Fernandez AP ; Samadi, A ; Unzeta, M ; Marco-Contelles, J ; Martinez-Murillo, R. JOURNAL OF PSYCHIATRY & NEUROSCIENCE: 42(1):59-69 (2017). DOI: 10.1503/jpn.150209
• Defective insulin signaling, mediated by inflammation, connects Obesity to Alzheimer Disease; relevant pharmacological therapies and preventive dietary interventions. Rodriguez-Casado A, Toledano-Díaz A, Toledano A. CURR ALZH RES.; 14(8):894-911 (2017). DOI: 10.2174/1567205014666170316161848
• In Vitro evaluation of Biocompatibility of Uncoated Thermally reduced graphene and carbon nanotube-loaded PVDF Membranes with adult neural stem cell-Derived neurons and glia. Defterali, C; Verdejo, R; Majeed, S; Boschetti-de-Fierro, A; Mendez-Gomez, HR ; Diaz-Guerra, E; Fierro, D; Buhr, K; Abetz, C; Martinez-Murillo, R ; Vuluga, D; Alexandre, M; Thomassin, JM; Detrembleur, C; Jerome, C; Abetz, V; Lopez-Manchado, MA; Vicario-Abejon, C. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY 4 (2016). DOI: 10.3389/fbioe.2016.00094
• Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy. Rey-Funes, M; Larrayoz, IM; Fernandez, JC; Contartese, DS; Rolon, F; Inserra, PIF; Martinez-Murillo, R; Lopez-Costa, JJ; Dorfman, VB; Martinez, A; Loidl, CF. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY 310 (11), pp.R1011-R101 (2016). DOI: 10.1152/ajpregu.00266.2015
• Thermally reduced graphene is a permissive material for neurons and astrocytes and de novo neurogenesis in the adult olfactory bulb in vivo
  Defterali, C; Verdejo, R; Peponi, L; Martin, ED; 4Martinez-Murillo, R ; Lopez-Manchado, MA; Vicario-Abejon, C. BIOMATERIALS 82, pp.84-93 (2016). DOI: 10.1016/j.biomaterials.2015.12.010
• Long-term dynamics of somatosensory activity in a stroke model of distal middle cerebral artery oclussion. Barrios, JA ; Pisarchyk, L; Fernandez-Garcia, L; Barrio, LC; Ramos, M; Martinez-Murillo, R; Gonzalez-Nieto, D. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 36 (3) , pp.606-620 (2016). DOI: 10.3390/ijms22105091
• Adrenomedullin Expression in Alzheimer’s Brain. Fernandez AP; Masa, JS ; Guedan, MA ; Futch, HS ; Martinez-Murillo, R. CURRENT ALZHEIMER RESEARCH: 13 (4): 428-438 (2016). DOI: 10.2174/1567205013666160229112725
• ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer’s disease Therapy. Marco-Contelles J, Unzeta M, Bolea I, Esteban G, Ramsay RR, Romero A, Martinez-Murillo R, Carreiras MC, Ismaili L. FRONT NEUROSCI: 10:294 (2016). DOI: 10.3389/fnins.2016.00294
• Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage. Ochoa-Callejero L, Pozo-Rodrigalvarez A, Martinez-Murillo R, Martinez A. SCI REP; 6:33495 (2016). DOI: 10.1038/srep33495
• Brain local and regional neuroglial alterations in Alzheimer’s disease: cell types, responses and implications. Toledano A, Álvarez MI, Toledano-Díaz A, Merino JJ, Rodríguez JJ.. CURR ALZH RES. 13(4):321-342 (2016). DOI: 10.2174/1567205013666151116141217
• Blood-based biomarkers of Alzheimer’s disease: diagnostic algorithms and new technologies. Carmona P, Molina M, Toledano A. ICURR ALZH RES.; 13(4):450-464 (2016). DOI: 10.2174/1567205013666151116130301
• Neuroglia in Alzheimer’s Disease: From Cohort to Contestant in the Disease Progression and its Therapy. Toledano A, Merino JJ, Rodríguez JJ. CURR ALZH RES.; 13(4):318-20 (2016). http://hdl.handle.net/10261/149792
• New concepts on the functionality of the nervous system: the revolution of the glial cells. ii. Glial responses keys in the pathogenesis and treatment of diseases of snc. Toledano A, Álvarez MI, Toledano-Díaz A, Rodríguez-Arellano JJ. AN REAL ACAD FARM 82, 1:51-67 (2016). ISSN (Online) 1697-4298

  http://hdl.handle.net/10261/150110

• The sigma 1 Receptor Engages the Redox-Regulated HINT1 Protein to Bring Opioid Analgesia under NMDA Receptor Negative Control. Rodriguez-Munoz, M; Sanchez-Blazquez, P ; Herrero-Labrador, R; Martinez-Murillo, R ; Merlos, M; Vela, JM; Garzon, J. ANTIOXIDANTS & REDOX SIGNALING 22 (10) , pp.799-818 (2015). DOI: 10.1089/ars.2014.5993
• Vibrational spectroscopic analysis of peripheral blood plasma of patients with Alzheimer’s disease. Carmona P, Molina M, López-Tobar E, Toledano A.
  ANAL BIOANAL CHEM 407 (25):7747-56 (2015). DOI: 10.1007/s00216-015-8940-7
• Astroglial cell subtypes in the cerebella of normal adults, elderly adults, and patients with Alzheimer’s disease: a histological and immunohistochemical comparison. Alvarez MI, Rivas L, Lacruz C, Toledano A.. GLIA 63(2):287-312. (2015). DOI: 10.1002/glia.22751
• Ultrastructural changes in the progress of natural Scrapie regardless fixation protocol. Casanova-Carvajal, O; Zeinoun, M; Urbano-Bojorge, AL; Bacha, F; Livi, JS; Agudo, E; Vargas, G; Sarasa R, Junquera C, Toledano A, Badiola JJ, Monzón M. HISTOCHEM CELL BIOL144 (1):77-85 (2015). DOI 10.1007/s00418-015-1314-6
• New concepts on the functionality of the nervous system: the revolution of the glial cells. I. The neuro-glial relationships. Toledano A, Álvarez MI, Toledano-Díaz A. AN REAL ACAD FARM VOL. 81, 1:11-18 (2015). ISSN (Online) 1697-4298. http://hdl.handle.net/10261/155110
• About the vibrational spectroscopy in the diagnosis of Alzheimer’s disease. Carmona P, López-Tobar E, Molina M, Toledano A. AN REAL ACAD FARM. 81, 1:19 –24 (2015). http://hdl.handle.net/10261/128196
• Methamphetamine Causes Degeneration of Dopamine Cell Bodies and Terminals of the Nigrostriatal Pathway Evidenced by Silver Staining. Ares-Santos, S; Granado, N; Espadas, I; Martinez-Murillo, R; Moratalla, R. NEUROPSYCHOPHARMACOLOGY 39 (5), pp.1066-1080 (2014). DOI: 10.1038/npp.2013.307
• Donepezil plus propargylamine+8-hydroxyquinoline hybrids as new multifunctional metal-chelators, ChE and MAO inhibitors for the potential treatment of Alzheimer’s disease. Wang, L ; Esteban, G ; Ojima, M ; Bautista-Aguilera, OM ; Inokuchi, T ; Moraleda, I ; Iriepa, I ; Samadi, A ; Youdim, MBH ; Romero, A ; Soriano, E ; Herrero, R ; Fernandez, APF ; Ricardo-Martinez-Murillo ; Marco-Contelles, J ; Unzeta M. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY: 80: 543-561(2014). DOI: 10.1016/j.ejmech.2014.04.078
• Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury. Genis, Laura; Davila, David; Fernandez, Silvia; Pozo-Rodrigalvarez, Andrea; Martinez-Murillo, Ricardo; Torres-Aleman, Ignacio. F1000Research 3, pp.28 (2014). DOI: 10.12688/f1000research.3-28.v2
• Morphological approach to assess the involvement of astrocytes in prion propagation. Hernández RS, Sarasa R, Toledano A, Badiola JJ, Monzón M.
  CELL TISSUE RES. 2014 OCT; 358(1):57-63. (2014). DOI: 10.1007/s00441-014-1928-3
• Variability in the effects of nicotine on different regions of the brain: changes in the concentration of superoxide dismutase isoforms. Toledano A, Álvarez MI, Toledano-Díaz A. Cent Nerv Syst Agents Med Chem.; 14(1):10-22. (2014). DOI: 10.2174/1871524914666140507162907
• Does Alzheimer’s disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II). Toledano A, Álvarez MI, López-Rodríguez AB, Toledano-Díaz A, Fernández-Verdecia CI. NEUROLOGIA 29(1):42-55 (2014). DOI: 10.1016/j.nrl.2011.05.004
• Hypothermia prevents gliosis and angiogenesis development in an experimental model of ischemic proliferative retinopathy. Rey-Funes M, Dorfman VB, Ibarra ME, Pena E, Contartese DS, Goldstein J, Acosta JM, Larrayoz IM, Martinez-Murillo R, Martinez A, Loidl CF. INVEST OPHTHALMOL VIS SCI 23-4-; 54:2836-2846 (2013). DOI: 10.1167/iovs.12-11198
• Could neurotransmitters influence neurogenesis and neurorepair after stroke?. Sanchez-Mendoza E, Bellver-Landete V, Merino JJ, Gonzalez MP, Martinez-Murillo R, Oset-Gasque MJ. NEUROPATHOL APPL NEUROBIOL 39:722-735 (2013). DOI: 10.1111/nan.12082
• Discrimination analysis of blood plasma associated with Alzheimer’s disease using vibrational spectroscopy. Carmona P, Molina M, Calero M, Bermejo-Pareja F, Martínez-Martín P, Toledano A. J ALZHEIMERS DIS.; 34(4):911-920 (2013). DOI: 10.3233/JAD-122041

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