> GROUP DETAILS:

The group has a strong translational character in the implementation of various animal models with immature brain injury and injury during development, as well as in other target organs.

The studies are directed to the pathophysiological knowledge and the search for therapeutic strategies, with special attention to the scope of the cannabinoid system.

In this regard, the group has become an international reference in this field, and together with strategic alliances with national and international leading groups and the pharmaceutical industry, the group has taken the step towards clinical trials.

> STRATEGIC GOALS:

1. Completing neonatal preclinical studies on efficacy and safety of Cannabidiol models of hypoxic-ischemic encephalopathy.
2. Initiating and leading a multinational clinical trial with cannabidiol and hypothermia in asphyxiated neonates.
3. Completing preclinical studies of efficacy and safety of Cannabidiol in models of neonatal cerebral ischemic arterial infarction.
4. Initiating and leading a clinical trial on cannabidiol in infants and children with refractory epilepsy.
5. Completing studies on the extracerebral multiorganic pathophysiology involved in brain damage and other diseases of inflammatory origin (lung, kidney, bladder), and the possible therapeutic role of cannabidiol.
6. Starting translational studies on ischemic intestinal damage.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

1. Cannabidiol in the treatment of neonatal hypoxic-ischemic brain damage.
2. Cannabidiol for the treatment of refractory epilepsy.
3. Multiorganic damage of inflammatory origin secondary to cerebral or systemic hypoxic-ischemic events: pathophysiology and therapeutic role of cannabidiol.

> OTHER GROUP MEMBERS

Álvarez Callejo, Lourdes
Armada Maresca, Maria Isabel
Arruza Gómez, Luis
De Santos  Moreno, Teresa
del Pozo Sanz, Aaron
Garía Ron, Adrián
Herranz Castillo, Gloria
Iglesias Fernández, Beatriz
Joyanes Abancens, Belén
Rodriguez Castaño, Maria José
Rodriguez de Alarcón García, Jaime
Silva Colmenar, Laura
Soto Beauregard, Carmen
Vargas Coronado, Carlos Javier
Vecino López, Raquel
Villa Cruz, María

> GROUP DETAILS:

The research group of pharmaceutical innovation in ophthalmology is dedicated to the design, development and evaluation of new formulations of topical ocular administration (topical and intraocular). The translational research developed by the group is directed towards the development of individualized treatments and design of new, more effective and safer therapies as key players in the field of health. Studies are addressed with a multidisciplinary approach.

The developed formulations are intended for the treatment of multifactorial diseases such as dry eye and glaucoma. Formulation on controlled release of active substances (anti-inflammatory, neuroprotective agents and antioxidants, among others) applied intraocularly are also developed for the treatment of posterior segment disorders (glaucoma, macular degeneration, diabetic retinopathy, retinitis pigmentosa ...) to avoid successive administrations of preparations. In most cases, these formulations require evaluation and application of new biomaterials for ocular administration. The group has specialized in the development of intraocular administration systems such as microspheres and in the microencapsulation of biotech products. The development of new systems for a controlled delivery of neuroprotective agents for the treatment of ophthalmic neurodegenerative diseases is also found among these techniques.

Once formulations are designed, they are characterized by the evaluation of pharmacotechnical properties and the in-vitro and in-vivo tolerance.  Studies on the efficacy are performed in animal models.

Technology transfer is carried out through the collaboration with companies and patent development. Indeed, one of them, related to a new artificial tear, has been transferred to a pharmaceutical company.

The group maintains collaborations with national and international groups and has obtained research projects of national public funding, from the EU and private funding projects with various pharmaceutical companies.

The Interventional Cardiology Unit of HUSC has played a key role in the evaluation of these technologies, being internationally renowned not only as a participant in major clinical trials within the field of coronary revascularization, but also as a promoter of its own research lines.

> STRATEGIC GOALS:

1. Development of new biodegradable systems of periocular and intraocular administration within the framework of the PANOPTES European Project.
2. Development and evaluation of a new formulation of biodegradable microspheres with neuroprotective agents in combination with antioxidant and anti-inflammatory agents, within the framework of the MAT-2010-18242 national research project.
3. Development of a new formulation of anti-inflammatory agents within the framework of the research project conducted with the Novagali Pharmaceutics laboratory.
4. Tolerance studies of topical ophthalmic formulations for the treatment of dry eye and glaucoma associated hypertension.
5. Development and evaluation of a new formulation for the treatment of dry eye within the framework of the FIS research project.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

1. Design and evaluation of controlled release systems (microspheres) of active substances of intraocular administration.
2. Optimization of ophthalmic formulations of topical administration.
3. Development of new formulations for the treatment of dry eye.
4. Development of new formulations of antihypertensive agents.
5. Micro and nanotechnology applied to the design of novel ophthalmic formulations.
6. Tolerance study of active substances, excipients and ophthalmic formulations.

> OTHER GROUP MEMBERS

Aragón Navas, Alba
Bravo Osuna, Irene
Brugnera, Marco
Caballo González, Mª Ángela
De las Heras Polo, Beatriz
Esteban Pérez, Sergio
García Herranz, David
Gonzalez-Cela Casamayor, Miriam Ana
Lopez Cano, José Javier
Pastoriza Abal, Pilar
Teresa Molina Martínez, Irene

> GROUP DETAILS:

The Ophthalmology Department of the San Carlos Clinical Hospital research group is well-established at a national and international level. It is part of the Thematic Network of the Cooperative Research at ISCIII OFTARED “Ocular pathology of aging, visual quality and quality of life” and part of the multidisciplinary research group from Complutense University of Madrid UCM-920415 “Design and evaluation and ophthalmic products and biomaterials”. The group works closely with the Ophthalmological Research Institute “Ramón Castroviejo” (UCM).

The main lines of work consists of the development and evaluation of antiglaucoma therapies, both at a medical and surgical level, the evaluation of treatments for aged related macular degeneration (AMD), uveitis and the dry eye syndrome (diagnosis, biomarkers and new treatments), the evaluation and development of diagnostic technologies in ophthalmology, the genetics of visual diseases and the development of new formulations for the treatment of ophthalmic pathologies.

Additional information: www.clinicovision.com and www.oftared.com.

> STRATEGIC GOALS:

1. Development of diagnostic algorithms based on the study of the retinal nerve fiber layer and the optic nerve for neuro-ophthalmic and neurological diseases.
2. Genetics of eye diseases (glaucoma and AMD). Identification of new candidate genes in congenital glaucoma.
3. Improvement of diagnostic systems and structural damage progression of glaucoma. Development of diagnostic and progression algorithms.
4. Analysis of the role of inflammation and oxidative activity in the pathophysiology of glaucoma.
5. Evaluation of new anti-glaucoma surgical procedures. Suprachoroidal trabecular implants and surgery.
6. Development of an in vivo assay system for the oxygenation/perfusion of the optic nerve.
7. Design of new diagnostic methods for ocular surface diseases.
8. Development of new formulations for the dry eye treatment.
9. Development and application of ophthalmic drugs delivery systems.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

1. Pathology of the aging eye.
2. Diagnostic and therapeutic technology.
3. Therapeutic innovation and ocular pharmacology.
4. Genetics.
5. Pathophysiology of glaucoma.
6. Dry eye and ocular surface diseases.
7. Uveitis and inflammatory intraocular diseases.
8. Vision and life quality.
9. Visual development.

> OTHER GROUP MEMBERS

Andrés Guerrero, Vanessa
Arriola Villalobos, Pedro
Benítez del Castillo, José Manuel
Borrego Sanz, Lara
Calvo González, Cristina
Carballo Álvarez, Jesús
Colina Jareño, Ainhoa
Cuiña Sardiña, Ricardo
Díaz Valle, David
Donate López, Juan
Escobar Moreno, María Jesús
Felipe Márquez, Gema
Fernández Vidal, Ana María
Fernández-Vigo Escribano, José Ignacio
García Sánchez, Julián
García Sáenz, Sofía
Gegúndez Fernández, José Antonio
Gómez de Liaño, Rosario
Iradier Urrutia, María Teresa
Jiménez Santos, María Aurelia
Lopez Abad, Consuelo
López Guajardo, Lorenzo
Martín Orte, Teresa
Martínez de la Casa, José María
Medina Ramirez, Lydia
Méndez Fernández, Carmen Dora
Méndez Fernández, Rosalía
Morales Fernández, Laura
Niño Rueda, Cristina
​Palomo Álvarez, Catalina
Reche Frutos, Juan
Romo López. Ángel
Sáenz-Francés San Baldomero, Federico
Sánchez Jean, Rubén
Santos Bueso, Enrique
Sanz Fernández, Juan Carlos
Torres Imaz, Ramón
Troyano Rivas, Juan Antonio
Valverde Megías, Alicia
Vázquez Molini, José María
Vico Ruiz, Eva

> GROUP DETAILS:

This group was created on the basis of the Psychiatry and Mental Health Research Group led by Professor Juan José López-Ibor until December 2014, and the subsequent incorporation of Professor Thomas Palomo, PI of the G19 Group of CIBERSAM. In order to continue the already established lines, and to strengthen the research in the area of ​​clinical and basic research of mental disorders, particularly in psychoses and related disorders, this group has a shared coordination between Prof. Tomas Palomo (Universidad Complutense de Madrid) and Dr. Blanca Reneses (San Carlos Clinical Hospital).

The activity can be grouped into two main research lines:

1) Neurobiological research of mental illnesses

This line includes studies in molecular biology, inflammation, neurocognition and neuroimaging in schizophrenia, in obsessive compulsive disorder, and other psychiatric disorders. The group has numerous bibliographical contributions.

In recent years, the group has been studying the staging, as a paradigm of development, progression, prevention and treatment of mental illness, schizophrenia, and more recently, depression, resulting in numerous publications.

Finally, a line of therapeutic innovation using neuromodulation techniques, through deep brain stimulation in psychiatric disorders resistant to conventional treatments, has been developed. This line has been conducted in collaboration with the research group of Prof. Juan Barcia from the Neuroscience area at IdiSSC.

2) Psychosocial factors associated with mental illness

A line of research in psychic trauma and its influence on mental illnesses, presenting a leading role in the European “Child Trauma Network” projectis included here together with a research line in the fight against stigma of mental illnesses, in close collaboration with European groups. This line already presents relevant publications.

> STRATEGIC GOALS:

1. Study of vulnerability genetic markers in schizophrenia and its biological functionality: Study of protein expression.
2. Characterization of the ANKK1 gene in relation to the dopaminergic role.
3. Relationship between genetic/molecular vulnerability factors and neurophysiological, neuropsychological and functional neuroimaging variables.
4. Study of the involvement of the immune system in vulnerability to schizophrenia and depression.
5. Study of mediators involved in the process of neuroinflammation in schizophrenia and depression.
6. Comparative analysis between schizophrenia and bipolar disorder: Genetic / molecular factors, cognitive function, neurophysiological variables, brain activation in light of neuropsychological tasks, and resting-state analysis.
7. Study of the evolution of schizophrenia from first psychotic episodes to advanced stages of the disease.
   - Genetic variables. Genes of the dopaminergic system, and other related systems. Epigenetics. Gene / environment (toxic) interaction.
   - Immunological and neuroinflammatory markers: immune response mediators, transcription factors, mediators of the HPA axis, enzyme activity.
   - Cognitive function. Evolution of the cognitive function.
   - Neurophysiology. Changes according to the evolution of the disorder in P50.P300 and IPP.
8. Functional neuroimaging. Activation studies in light of cognitive tasks, connectivity analysis (DTI), and resting-state.
9. Study of the influence of substance use in the pathogenesis, evolution, cognitive functioning, neurophysiological responses, and functional neuroimaging of psychosis.
   - Study of neurodegeneration during schizophrenia by neuroimaging analysis, and the study of associated genetic, epigenetic and environmental factors.
10. Study of neuroinflammatory markers related to the vulnerability to different psychiatric disorders, both in animal models and patients.
    - Study of the pathophysiological mechanisms and pharmacological bases of brain damage processes induced by exposure to stress, in view of the relationship between exposure to stress and many neuropsychiatric disorders.
    - Identification of new possible therapeutic targets, and evaluation of neuroprotective strategies during these processes.
11. Clozapine usefulness in first psychotic episodes: clinical evolution, cognitive evolution and neuroimaging analysis.
12. Identification of intracranial stimulation areas, with therapeutic value in obsessive compulsive disorder and other treatment-resistant psychiatric diseases.
13. Development of prevention programs in psychiatric illness stigma within the healthcare environment.
14. Establishment of a preventive program for psychic trauma consequences, applicable in situations of disasters and catastrophes.
15. Study of the impact of schizophrenia on health, psychosocial adjustment, quality of life, individual disability levels and in the use of facilities by these patients and their influence on comorbidity.
16. Contribution to the development of a clinical staging system in depressive disorders and schizophrenia.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

1. Molecular and genetic basis of neuropsychiatric disorders.
2. Genetic / molecular and environmental vulnerability to schizophrenia.
3. Evolution of schizophrenia: first psychotic episodes. Neurodegeneration.
4. Addictive disorders, psychoses and Dual Pathology.
5. Cognitive, genetic, neuroimaging and neurophysiological comparative study between schizophrenia and bipolar disorder.
6. Neuroinflammation study as an ethiopathogenic factor in mental illness. Stress Study.
7. Molecular neuropsychopharmacology. Searching for biomarkers and new therapeutic targets.
8. Treatment of schizophrenia in different stages.
9. Neuromodulation, connectivity and neurobiological basis of psychiatric disorders.
10. Neurocognitive research in disorders of obsessive-compulsive spectrum and other psychiatric illnesses.
11. Research of factors involved in the stigma of mental illness.
12. Research in preventive factors and early intervention in post-traumatic stress disorder and psychological trauma.
13. Staging study as a paradigm of prevention, progress and treatment of mental illness.
14. Psychosomatics. Psychiatric morbidity in medical-surgical patients. Population psychiatric morbidity and utilization of health care resources.
15. Aging and dementia.

> OTHER GROUP MEMBERS

Argudo Carel, Isabel María
Del Río Vega, Julia María
Figuera Álvarez, Diego
Fraguas Herraez, David
Fuentenebro de Diego, Filiberto
Gallastegui Galán, Jose Antonio
Gallego Deike, Lucía
García-Albea Martín, Julia
López-Ibor Alcocer, María Inés
Molina Ruiz, Rosa María
Oca Bravo, Laura
Pelaz Antolín, Antonio
Pérez Martínez, Sara
Pérez Moreno, Mª del Rosario
Ramos García, Isabel
Rodriguez Toscano, Elisa
Saiz González, María Dolores
Serván Rendón-Luna, Beatriz
Sevilla Llewellyn-Jones, Julia
Tur Salamanca, Nuria
Zamarro Arranz, Mª Luisa

Support Research Staff
Rosario Pérez Moreno (HCSC)

The group also works in collaboration with UCM G19 Groups at CIBERSAM (IP Tomas Palomo), including Vicente Molina (Neuroimaging University of Valladolid), Janet Hoenicka (genetics and molecular biology, San Joan de Deu Hospital of Barcelona), Marta Moreno (now at Columbia University, NY, connectivity and transcranial magnetic stimulation) and Javier Caso (neuroinflammation, UCM); and the UCM “Psychosis and Addictions” Group (IP Tomas Palomo), among others.

> GROUP DETAILS:

The group of advanced research in personality disorders, aggression and impulse control has steadily grown over the last fifteen years, on a scope consisting of severe behavioral pathologies, other than schizophreniform disorders, bipolar disorders or organic-brain disorders. The group covers the so-called personality impulsive disorders (borderline, histrionic, antisocial), explosive aggression disorders (intermittent explosive disorder), self-harm disorders (self-injurious behavior or self-mutilation, suicide) and pathological impulsive disorders (nervous bulimia and related disorders, pathological gambling and other disorders of impulse control).

The research has covered from the biological study of impulsive personality traits (Carrasco et al, 1994, Diaz-Marsá et al, 2000), through neurochemical (serotonergic depletion, hypothalamic-pituitary response, platelet MAO activity) and psychological indices (personality structure, neuropsychological function, coping mechanisms) of aggressive and eating impulsive disorders (Carrasco et al, 2000, 2007, 2010) (Diaz-Marsá et al, 2007, 2009) to the current research on neuro-impulsivity (RNM, magnetoencephalography) of involved psychogenic factors, such as childhood trauma, emotional and affective response, and attention deficit disorder.

Dr. José Luis Carrasco, the initiator of the research, is Professor of Psychiatry and Head of Section at the San Carlos Hospital. He is a renowned researcher in the mentioned areas and has high impact publications, research projects and outstanding participation in conferences and scientific societies. He is co-principal investigator, together with Prof. Juan José López-Ibor, from a group within CIBERSAM at HCSC, with the active collaboration of Dr. Diaz-Marsá (although she is present in another research group of Psychiatry) and a team of psychiatrists and psychologists from CIBERSAM and HCSC, in a range that goes from teams of experienced clinicians and researchers,like Dr.  Julia del Río and Dr. M.Dolores Saiz (senior researchers at CIBERSAM), to youngnewly incorporated postdocs with great projection.

> STRATEGIC GOALS:

1. Describing specific abnormalities in brain functional response of the impulsive personality disorders using brain and structural imaging.
2. Confirming the evidence of prefrontal dysfunction in borderline personality disorder using neuroimaging and neuropsychological tests.
3. Demonstrating the existence of specific abnormalities in functional brain response to food impulsive disorders (bulimia and anorexia-bulimia).
4. Finding evidence of the pathogenic role of various factors in the emergence and the development of personality disorders, aggression and impulse control, including: 
   - Severe childhood trauma (physical and sexual abuse)                                                      - Attention and neuropsychological deficits in childhood neurodevelopmental disorders.
5. Finding groundwork for psychobiological subtyping of borderline personality, allowing a more effective clinical approach for this heterogeneous construct.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

1. Study of biochemical indicators associated with impulsive personality disorder and the impulse control disorder: corticoid receptors, cytokines and cellular inflammatory factors.
2. Study of the psychobiological subtyping of borderline personality, through psychological and neuropsychological characterization.
3. Study of factors associated with neurodevelopmental personality disorders: Childhood trauma, attention deficit and family affective response. Brain imaging of emotional response in borderline personality disorder: MRI and magnetoencephalography.
4. Study of brain dysfunctions in eating disorder, using functional neuroimaging in response to specific stimuli. Research of new pharmacological and psychological therapies in borderline personality disorder.
5. Study of the effectiveness of neurocognitive rehabilitation in borderline personality disorder.

> OTHER GROUP MEMBERS

Díaz Marsá, Francisca Marina
Fernández García Andrade, Rafael
Gómez Merino, Patricia
González Vives, Sara
Mellor Marsá, Blanca
Montes Montero, Ana
Morón Nozaleda, María Dolores
Vázquez Rivera, Susana 

> GROUP DETAILS:

The team works in a multidisciplinary way since the late 70s. Initially, it consisted of specialists from the Psychiatric, Neurophysiology, Nuclear Medicine and Endocrinology Services from the Hospital Clínico San Carlos, with a common interest in Neuroscience. Over time, the group has been structured and the participation of physicians in the Neurology and Geriatric Services has increased. Extensive clinical, teaching and research activities in different pathologies of this field have resulted from this work, the first publications appearing in 1979. Since 2000, the team has a Molecular Genetic Research Laboratory within the Research Unit of the Hospital Clínico San Carlos, and since early 2010, the chief of the Magnetoencephalography Center of the Polytechnic University of Madrid joined the group, responding to the current need of new technologies in the field of neuroimaging and genetics, in our line of multidisciplinary work.

Our activity is based on two lines of research conducted by our group:

• The study of biological databases and genetic susceptibility to neuropsychiatric diseases. The study of cognitive disorders, and their relationship with genetic markers and functional brain imaging in: dementia, bipolar disorder and schizophrenia.
• Genetic, cognitive and neuroimaging evolution of markers from Mild Cognitive Impairment to Dementia: Identification of variants of genes involved in the pathophysiology of dementia, inflammation and brain connectivity, as well as early cognitive and brain imaging defects predictors of the progression to Dementia, in subjects with Mild Cognitive Impairment defects. Studying the anatomical and functional connectivity in patients with Mild Cognitive Impairment and Alzheimer's disease.
  

> STRATEGIC GOALS:

• Defining risk genes for the development of bipolar disorder, schizophrenia, Mild Cognitive Impairment (MCI), Alzheimer’s Disease (AD) and Morbid Obesity (OM).
• Defining cognitive, genetic and neuroimaging early markers of DCL evolution to dementia.
• Determining whether measures of functional connectivity using magnetoencephalography can differentiate between patients with AD, MCI and control subjects.
• Characterizing anatomical connectivity differences, using diffusion tensor imaging in patients with AD, MCI and control subjects.
• Delineating the possible existence of a relationship between genetic profiles and parameters of anatomical-functional connectivity, and cognitive function in patients with MCI and AD and in control subjects, and their impact on the evolution of DCL to EA.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

• Studying biological databases and genetic susceptibility to neuropsychiatric diseases, based on measurable endophenotypes by neuroendocrine, neurophysiological, and psychological and neuroimaging tests.
• Genetic, cognitive and neuroimaging markers of evolution from Mild Cognitive Impairment to Dementia.

> OTHER GROUP MEMBERS

Cabranes Díaz, José Antonio
Maestu Unturbe, Fernando 
López García, Maria Eugenia 
Paul Lapedriza, Nuria 
Canuet Delis, Leónides
Bajo Bretón, Ricardo

> GROUP DETAILS:

The Neurotransmission and Neuromodulation group at CNS is a basic research group composed by professors from the Departments of Physiology and Biochemistry of the Faculty of Veterinary Medicine, from the Department of Physiology of the Faculty of Medicine of the UCM, and several granted or contracted pre- or post-doctoral students.

The overall objective is to study the basic mechanisms of excitability, neurotransmission and neuromodulation, as well as the molecular mechanisms involved in the synaptic maturation, using different cell models (primary cultures of cerebellar granule neurons, cortical neurons) and animals. Different experimental approaches (electrophysiological, biochemical, molecular biology and imaging techniques) are possible thanks to the multidisciplinary training of the group members, and to different national and international collaborations.

Different synaptic alterations are the cause of many diseases, among which fragile X syndrome is the second most common cause of mental retardation in humans and is caused by the absence of the FMR protein. In the brain, this protein is exclusively expressed in differentiated neurons, it is detected in the synapse and, although its function is not yet exactly known, it is important in the synaptic development and in the control of the synaptic function. Indeed, a high degree of immaturity is observed when this protein is not expressed. Therefore, we consider of great interest, the transfer of the acquired knowledge about the mechanisms of control of the synaptic function over the last years, within the study of this pathology.

Today, four research lines, including several sub-lines, are being developed:

• Control of the synaptic function (exocytosis, vesicle cycle, synaptic silencing) by metabotropic receptors. Study of the fragile X syndrome in an animal model.
• Regulation of the synaptic function (vesicular cycle, expression of postsynaptic AMPA receptors ...) by the NO / cGMP signaling pathway. Analysis of the fragile X syndrome in an animal model.
• Relationship between brain glutamate, plasmatic glutamate and ischemic damage.
  Imaging techniques for the evaluation of ischemic damage.
• Study of the intrinsic excitability of the plasticity in the hippocampus developing rat.

> STRATEGIC GOALS:

• Fundraising: Maintaining current funding levels. Increasing the participation in network projects, by the establishment of more partnerships with other basic and clinical groups with an interest in the study of diseases, such as autism (fragile X syndrome), epilepsy or ischemia.
• Publications:
   Keeping publications (20-25 publications / 5 years) at the first quartile and improving the Impact Factor.
• Thesis: Completion and presentation of nine to ten doctoral theses in 2012-2016.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

• Control of the synaptic function by presynaptic metabotropic receptors. Analysis of fragile X syndrome in an animal model.
• Role of the NO / cGMP in synaptogenesis, synaptic functional maturation. Analysis in a model of imperfect synaptogenesis (Fragile X syndrome)
• Relationship between brain glutamate, plasmatic glutamate and ischemic damage.
• Studying the intrinsic excitability of the plasticity in the hippocampus developing rat.

> OTHER GROUP MEMBERS

Colino Matilla, Asunción
García Font, Nuria
García Pascual, Mª Ángeles
Martín Herranz,  Ricardo
Oset Gasque, María Jesús
Rampérez Martín,  Alberto
Sánchez-Aguilera López, Alberto
Sánchez-Prieto Borja, José
Triguero Robles, Domingo
Vicente Torres, Mª Ángeles

> GROUP DETAILS:

Themain focus of our researchlieson the study of nucleotide receptor signalling at the the Central Nervous System and its role in processes such as survival, differentiation and neuronal regeneration. The diverse functions regulated by nucleotides are triggeredby the activation of both ionotropic (P2X) and metabotropic (P2Y) receptors,both widely distributed in different neuronal and astrocytic cell populations. Recently, we described the neuroprotective properties of P2Y13 and P2X7 receptors against different apoptotic stimuli, as well as their capacityto enhance thesurvival function of the neurotrophin BDNF, by regulating MAPK and GSK3 signaling proteins. In addition, these signaling mechanisms are also involved in transcriptional regulation of P2X7 receptor. A new promising research line is focused on the mechanisms regulatingadult neurogenesis and the involvement of nucleotide receptors in this process.

> STRATEGIC GOALS:

1. Study of the differential signaling of nucleotidic receptors, particularly the ionotropic P2X7 receptor, in neurons and astrocytes from distinct brain areas, cerebellum, cortex and hippocampus.
2. Study of the neuroprotective effect of nucleotides in light of different types of stress, such as oxidative stress and genotoxic stress (induced by exposure to ultraviolet radiation and cytotoxic drugs), and the intracellular mechanisms responsible for this protective effect. The study will focus on the Nrf2 / HO1 antioxidant axis, the MAP kinases cascade, the GSK3 protein, as well as on induced genes that could be mediating protective and repairing responses.
3. Interaction of nucleotidic receptors with other survival factors, such as neurotrophins and glutamate.
4. Study of the communication between granular neurons and astrocytes of the cerebellum on the release of survival factors, neurotrophins, cytokines and ATP itself.
5. Study of growth factors as regulators of the gene expression of nucleotide receptors, especially the P2X7 receptor.
6. Study of the coupled signaling of nucleotidic receptors in macrophages and their role in the inflammatory function. Interaction with other signs of inflammation.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

1. Study of the nucleotide receptor signaling and physiology in neuron and astrocyte populations of the cerebellum, cortex and hippocampus.
2. Role of nucleotide receptors in neuroprotection and neurodegeneration.
3. Interaction of nucleotidic receptors with other neurotransmitter systems and growth factors.
4. Transcriptional regulation of nucleotide receptors.
5. Role of the nucleotidic receptors in inflammation and neuropathic pain.

Arribas Blázquez, Marina
Artalejo Rodriguez, Antonio
Barahona Gomariz, Maria Victoria
Bianchi, Carolina
Bustillo Merino, Diego
Di Lauro, Caterina
Díaz Hernández, Miguel
Garcia Delicado, Esmerilda
Gascón Jiménez, Sergio
Gómez Villafuertes, Rosa
Gil Redondo, Juan Carlos
Miras Portugal, María Teresa
Queipo García, María José
Olivos Orés, Luis Alcives
Ortega, Felipe
Perez Sen, Raquel
Sánchez Nogueiro, Jesús

> GROUP DETAILS:

This research group aims to promote the reorganization and repair of damaged brain through neurosurgical procedures.

For this purpose, brain stimulation through classical functional neurosurgery is used to restore the lost equilibrium upon pathological processes. To this end, physiological experiments will be used for the identification of new stimulation targets, and functional imaging techniques (fMRI, DTI, MEG, Deeg, dECoG), for the optimization of stimulation targets in Parkinson’s disease and other movement disorders, such as epilepsy, pain, and psychiatric disorders like obsessive-compulsive disorder, depression, schizophrenia, aggressiveness, impulsivity, memory disorders and dementia.

Secondly, paired brain stimulation will be used as a method to induce plastic changes in the brain, allowing the extended resection of brain tumors and the treatment of brain injuries accompanied by brain injury (such as stroke), cortical degeneration (dementias) or injuries associated with defects in brain development, such as schizophrenia or personality disorders.

Thirdly, adult cells of autologous or heterologous origin will be used to promote neural regeneration after brain damage, either by the use of stem cells from fat, from involving olfactory glial cells or from stem cells differentiated into neural precursors.

Finally, biomaterials for the induction of axonal regeneration and cortical reconstruction with interest in neurodegenerative (Parkinson, ALS), vascular (stroke) or traumatic diseases will be used.

> STRATEGIC GOALS:

1. Application of biomaterials for neuronal regeneration and reconstruction in models of stroke and Parkinson’s disease.
2. Promotion of the plasticity by the use of cortical stimulation, plus rehabilitation, in low-grade gliomas, pain and psychiatric illnesses.
3. Identification of new targets for deep brain stimulation.
4. Launching of the cleanroom.
5. CELICTUS clinical trial.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

1. Target identification and optimization for brain stimulation using functional neuroimaging techniques.
2. Induction of brain plasticity by paired stimulation.
3. Brain reconstruction using stem cells.
4. Use of biomaterials for brain regeneration and reconstruction.
5. Neurosurgical technology based on imaging and neurophysiology.

> OTHER GROUP MEMBERS

Barca Fernández, Idoya
Esteban García, Noelia
Fernández García, Carla
Fraile Pereda, Adela
González Hidalgo, María de las Mercedes
López Cantó, Oleza
Sánchez Sánchez de Rojas, Leyre

The group has local (Neurology, Psychiatry, Neurophysiology, Neuroimaging) and external collaborations, including Manuel Monleón from The Biomaterial Center of Valencia, and Jose-Manuel García Verdugo from the University of Valencia.

> GROUP DETAILS:

This group of researchers is composed by clinical specialists from the Neurology Service of the Hospital San Carlos and from other related services within the Institute of Neuroscience. Furthermore, they are also involved in the Clinical Neuroscience research group at UCM.

The common interest of these researchers is their work on projects and research programs in neurological and neuromuscular diseases, from the methodology, epidemiology, mechanisms, clinic and therapeutics in coordination with other groups of the Institute.

Thematic research projects can be classified into:

• Methodology and validation of tools in the field of epilepsy, dementia, headache, movement disorders, stroke and ALS.
• Epidemiological research, especially in the ALS field, neuroimmune diseases, headache and movement disorders.
• Research on disease mechanisms, especially in demyelination, ALS, epilepsy and neurodegenerative diseases.
• Clinical research in all the above areas, being especially relevant in headaches, together with description of new entities, movement disorders and stroke.
• Therapeutic research in all cited areas in clinical trials with external and academic funding as well as in experimental models.
• Research in cognitive neuroscience and its counterpart in neuroimaging.
• Research on sleep disorders.
• Research in the clinical application of neurophysiological techniques.
• Research on the response in the neurogenesis of neurological diseases.
• Research in neurology management, access to health care units and validation of actions on neurological patients.

The group is organized into areas of greater experience, while maintaining a common link in common projects. These areas are epilepsy, movement disorders, neuroimmune diseases, Alzheimer’s and related diseases, stroke, headache and migraine, ALS and neuromuscular disease, sleep and clinical neurophysiology.

The group has strong presence in publications and scientific activity in neurological clinic and has organized a research training program in which all neurology assigned residents from the Hospital are provided of a personal research tutor along the process.

Resources are shared with other groups at the Institute of Neurosciences at HCSC. As far as for translational research, the storage of clinical material and the structuring of databases are available in accordance with the current legislation. Furthermore, a storage area of ​​historical clinical research is also available.

> STRATEGIC GOALS:

• Study of the impact of neurological diseases in neurogenesis.
• Cytotoxicity projects in ALS.
• Clinical and neuroimaging biomarkers in neurodegenerative diseases.
• Epidemiology of infrequent headaches.
• Development of prognostic factors for epilepsy.
• Rating of factors associated to narcolepsy.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

• Cognitive neuroscience and neuroimaging.
• Neuroimmunology and neuroimmune diseases.
• Movement disorders.
• Epilepsy.
• Stroke and migraine.
• Neurodegeneration in neurological diseases.
• Sleep disorders.
• Neurophysiology applied to neurological diseases.
• Tools for the managing of neurological patients.

> OTHER GROUP MEMBERS

Alonso Frech, Fernando
Balugo Bengoechea, Paloma
Benito Martín, Soledad
Cabrera Martín, María Nieves
Carreras Delgado, Jose Luis
Catalán Alonso, María José
Corrochano Sánchez, Silvia
Cuadrado Pérez, María Luz
Delgado Alonso, Cristina
Galán Dávila, Lucía
García Morales, Irene
García-Ramos García, Rocío
Gómez-Escalonilla Escobar, Carlos
Gómez-Pinedo, Ulises
González Gutiérrez, José Luis
Hernandez Lorenzo, Laura
Horga Hernández, Alejandro
Martín Albarrán, Susana
Martínez Orozco, Francisco Javier
Martínez Poles, Javier
Matías-Guiu Antem Jordi
Montero Escribano, Paloma
Moreno Jiménez, Lidia
Moreno Ramos, Teresa
Palacios Sarmiento, Marta
Parejo Carbonell, Beatriz
Porta Etessam, Jesús
Pytel, Vanesa
Romeral Jimenez, María
Sanclemente Alamán, Inmaculada
Torre Fuentes, Laura
Villalibre Valderrey, María Isabel

> GROUP DETAILS:

The Brain Mapping Center has extensive experience in the study of brain function, through EEG evoked potential techniques in humans, and microPET functional imaging in animals.

The center presents the following units:

• Brain Mapping Laboratory: High resolution EEG; Evoked potentials; Equivalent dipoles to neuronal sources.
• PET / CT Imaging Laboratory for small animals: ARS Albira tomography.

> STRATEGIC GOALS:

• Molecular imaging in animal models of the disease.
• Role of the serotonergic system through the 5HT-1A receptor in neurodegenerative diseases or in the development of mesial sclerosis in epileptogenesis.
• Evaluation of PET hypoxia tracers as specific markers of cerebral stroke penumbra.
• Study of the influence of emotional content in different word processing aspects using EEG records.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

• Exploration of the serotonergic system: PET tracer imaging of 5HT1A serotonergic receptor agonists, and the study of the involvement of these neurons in epileptogenesis or neuronal death during Alzheimer's disease.
• Molecular imaging in experimental models of stroke using positron emission tomography techniques in rodents.
• Interaction and multimodality of functional neuroimaging techniques: MRI and PET.
• Interaction between language and emotion by EEG.

> OTHER GROUP MEMBERS

De Cristóbal Blanco, Javier
Delgado Wallace, Mercedes
Fernández de la Rosa, Rubén
García García, Luis
Hinojosa Poveda, José Antonio
Moreno Montes, Eva María
Rincón Pérez, Irene

> DETAILED INFORMATION ABOUT THE GROUP:

Our main research line is the study of the implication of environmental factors in the etiopathogenesis of degenerative diseases and their possible utility as biomarkers in the prognosis of these diseases and in the response to treatment, as well as the study of the mechanisms involved in the interaction between these environmental factors and the possible susceptibility genetic factors. In 1997 we began a new line of pioneering research in Spain: the study of the possible involvement of herpesviruses in the etiopathogenesis of multiple sclerosis; internationally validated detection protocols and multiple collaborations have been established at national and international levels, and a number of projects have been developed that have been financed on a continuous basis both public (FIS) and privately, which has allowed us to publish more than 40 international articles on this particular topic. In recent years, the study of other environmental factors, such as the JC virus, vitamin D, metabolites of the microbiota and the study of human endogenous retroviruses (HERVs) have also been included in this pathology and in other degenerative diseases. Finally, along this time, we have also studied the interaction between different genetic factors of susceptibility and environmental factors, in order to deepen the possible mechanisms involved in the origin of these diseases.

> STRATEGIC GOALS:

1. To study the possible mechanisms through which herpesviruses would be involved in the etiopathogenesis of different degenerative diseases, and in their interaction with genetic factors of susceptibility to these diseases, through the analysis of viral loads, antibody titers and expression of viral microRNAs.
2. To study the mechanisms involved in the reactivation of the JC virus, causal agent of progressive multifocal leukoencephalopathy, in MS patients treated with natalizumab.
3. Analysis of vitamin D as a possible modulator of the immune system and the genetic factors associated with its levels and its activation and degradation processes.
4. Study of human endogenous retroviruses (HERVs) as genetic and environmental factors involved in the development of different degenerative diseases.
5. Analysis of circulating metabolites produced by gut microbiota and their interaction with the immune system and/or the central nervous system in patients with degenerative diseases.

> RESEARCH LINES LINKED TO STRATEGIC GOALS:

1. Identification of the environmental factors involved in the onset and progression of degenerative diseases.
2. Study of the gene-environment interaction in degenerative diseases.
3. Optimization of Molecular Biology techniques applied to the study of the different environmental factors associated with degenerative diseases.

> OTHER GROUP MEMBERS

Domínguez Mozo, Mª Inmaculada
​García Martínez, María Ángel
Pérez Pérez, Silvia