Hari Shanker Sharma, Ph D (BHU), Dr Med Sci (UU) is the Director of International Experimental Central Nervous system (CNS) Injury & Repair (IECNSIR) at University Hospital, Uppsala University, Sweden. He is a qualified Neuroanatomist and experimental neurpathologist trained in Germany, Switzerland, Hungary, Sweden and USA. His main research interest is currently focused on neurotoxicity of nanoparticle and nanowired drug delivery of agents for enhanced neuroprotection in a variety of CNS insults or neurodegenerative diseases in relation to the blood-brain barrier (BBB) function. He has authored more than 250 original research papers and edited several book volumes or Progress in Brain Research series.

Recent advancements in bionanotechnology lead to the development of several nanoformulation to deliver drugs to the central nervous system (CNS) for enhancing the therapeutic potential of the parent compounds. Nanodrug delivery could allow the active compounds to enter faster in the CNS in high quantity and may remain there for prolonged periods of time due to slower degradation resulting in enhanced therapeutic effects. For this purpose, several techniques for nanodrug delivery are used e.g., incorporation of drugs into soft nanoparticles, carbon nanotube as well as tagging them to nanowires made from different nanomaterials viz., SiO2, Cu, Ag, or Al. However, the neurotoxic effects of nanomaterials per se on the CNS structure or function are still not well investigated. Thus, the need of the hour is to evaluate possible effects of nanomaterials on the neurotoxicity of the CNS before they are used for neurorepair. In this regard microscopy is the only technique that can precisely focus on the structural alterations of the CNS components following nanodrug delivery for neurorepair purposes. Since last decade, our laboratory is engaged in exploring the role of nanoparticles and/or nanowired drug delivery on structural changes on the CNS in animal models using both light and electron microscopy in vivo situations. In this review salient features of nanoneurotoxicity and nanoneuroprotection as revealed by microscopical techniques are discussed.

C. Miguelez defended her PhD thesis in 2008 at the UPV/EHU. Her research focuses on non-motor complications of Parkinson’s disease and involvement of monoaminergic systems in the expression of L-DOPA induced dyskinesias. In 2009, CM joined the group of J. Baufreton at the Institut des Maladies Neurodegeneratives at the University of Bordeaux. The core of her postdoctoral training was to study the GABAergic synaptic transmission in the basal ganglia during parkinsonism. Since 2012, CM is assistant professor in Pharmacology at the UPV/EHU. Dr. Miguelez has currently published 11 scientific papers

Parkinson’s disease is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra compacta. Currently, pharmacological treatment improves motor sympthoms in the early stages of the disease, but long-term use of these drugs leads to invalidating side effects and severe disability. The early diagnosis and the availability of new therapies that slow or halt the progression of the disease are needed for improving the quality of life of these patiens. In this sense, an important goal in Parkinson’s disease research is to identify neuroprotective therapies that protect neurons from degenerating. Althought it is impossible to predict with exactitude the therapeutic and side effects of new compounds, the use of reliable animal models during preclinical validation is a must. At present, different types of animal approaches can be used, such as toxin-induced, gene-based or viral vector-mediated models. The first group generally includes 6-hydroxydopamine and MPTP administration and shows features of the human disease. Gene-based models includes various types, such as alpha-synuclein or genetic leucine-rich repeat kinase 2 transgenic mice. Lately, also viral vector-medited modelling has been used for specifically overspressing alpha-synuclein in defined areas of the brain. Despite the variety, none of the mentioned models are perfect for testing neuroprotective strategies, however, each of them offer relevance and usefulness for developing new neuroprotection therapies.

MD and PhD from University of Zaragoza (Spain), Full Professor for Human Anatomy and Embryology at the Department of Neuroscience (UPV-EHU). He has supervised 20 Ph.D. works. He has been Invited Professor and Visiting Researcher at several European (Free University of Berlin, MCNN Birmingham) and Latinamerican universities (Chile, Valparaiso, Mendoza…). His main Research interests are in neuropathology and neurobiology of adaptive postnatal changes in the microvasculature of CNS in health and disease. He has been autor of 120 original papers and 33 reviewed book chapters. He is actively involved in cooperative networking in neuroscience research.

Neuroscience is a paradigm of multidisciplinarity. In the same way “CNS Injury and Repair” is a meeting point for experts from various fields, which converge in this key topic looking for a better understanding of the tipical features in the sickening and healing of CNS. In this singular system concepts like neuroprotection, neuroregeneration, neurorescue, neurotrophism or neuroplasticity must be carefully defined and delimited to build a common language allowing a right understanding among researchers of the jumbled processes ocurred in CNS. Initiatives like the UFI-programme promoted by the University of the Basque Country run in this direction making possible and interesting the encounter of researchers around a hot topic, and encouraging the collaborative works. Four crucial points should be taken into acount in the approaching to research in CNS Injury & Repair. Co-morbidities like diabetes, hypertension, colesterol etc co-exist or are previously to the CNS Injury, these factors may complicate the repair and neuroregeneration. We still have a poor understanding of the Blood Brain Barrier modulation, what difficults the design of therapeutic strategies. The emerging nano-formulations have physical and biological characteristics that regarding the behaviour of tissular barriers remain still unclear, being a challenge. And about the potential Neurotoxicity of some nanostructures. In fact, it remains to be determined, being a deeper knowledge in the draining pathways extremely necessary

Harkaitz Bengoetxea obtained his PhD at the University of Basque Country in 2006 and postdoctoral studies from Consiglio Nazionale delle Ricerche (Pisa, Italia). He is Professor of Anatomy since 2007 at the Department of Neuroscience of the University of Basque Country. He has published 16 papers, directed 1 PhD and participates in several research projects. His research fields focus on the neurogliovascular unit and the effects of rearing environments over these brain elements.

Environmental enrichment (EE) consists of large and engaging cages where the animals are reared in large social groups. They have a wide variety of objects that increase levels of novelty and complexity. Rats have access to voluntary physical exercise through running wheels. This environment induces sensory, cognitive and motor stimulation and promotes activation, signaling, and neuronal plasticity in various brain areas. At anatomical level, increases cortical weight and thickness, dendritic branching and length, and size of synapses in some neuronal populations. Also increases hippocampal neurogenesis, inhibits apoptosis, and has strong effects on the plasticity of neural connections. Astrocytic morphology was changed due to exposure to enriched environment. Size and density of astrocytes of visual and somatosensory cortices were increased and the same occurs with vascular density. Most of these changes are in concordance with higher levels of angioglioneurins, molecules that affect neural, vascular and glial cell processes. Therefore this strategy mediates neuroprotective effects in a wide variety of brain disorders. EE delay onset of motor deficits and ameliorate neurodegenerative losss of cerebral volume in Huntington´s disease mice models. Also induce beneficial cognitive effects in mouse models of Azlheimer´s disease. In Parkinson´s disease animal model, EE can regulate the generation of neural precursors in the substantia nigra. Enrichment delayed onset of cognitive deficits and depression-like behaviors, or was able to ameliorate behavioral abnormalities in rodent models of psychiatric disorders, like schizophrenia. EE also act synergistically with other approaches like drug or cell therapies to facilitate neuroprotection and brain repair.

Assistant professor in the Department of Pharmacology at the UPV/EHU. T. Morera got her PhD in Pharmacy in 2008. During the predoctoral period she performed in vivo electrophysiological experiments in Basal Ganglia nuclei. Moreover, she made two stages in national and international laboratories in order to learn how to perform in vitro electrophysiological recordings. Thanks to a postdoctoral grant, she moved to the College the France (Paris), where she acquired technical skills to perform in vitro whole cell patch-clamp and in vivo intracellular recordings. After 2 years, she returned to the UPV/EHU where she continued her academic career and research.

The endocannabinoid system is a signalling pathway composed of at least two G-protein coupled receptors (cannabinoid CB1 and CB2) and their endogenous ligands. It is involved in several central nervous system functions. Evidence has accumulated over the last few years suggesting that cannabinoids could be promising neuroprotective molecules based on their capability to reduce excitotoxicity by suppressing glutamatergic activity, to inhibit certain calcium channels and to decrease the oxidative injury that causes degeneration. Moreover, cannabinoids exert anti-inflammatory effects by inhibiting glial activation and are able to reduce the cerebrovasoconstriction produced by endothelium-derived factors. Thus, cannabinoids may provide neuroprotective effects through both receptor- and non-receptor mediated mechanisms in different neurodegenerative disorders including Parkinson's disease (PD). In fact, exogenous and endogenous cannabinoids have been shown to blockade neurodegeneration in a variety of in vitro and in vivo models of PD. In view of the results obtained in preclinical research, the endocannabinoid system may represent a promisint target for developing effective neuroprotective clinical therapies.

Ane Murueta-Goyena Larrañaga is a PhD student in Neuroscience in the University of the Basque Country. Her thesis research is focused on determining the long-term consequences of MK-801 administration in behavior and in the density of different GABAergic populations.

The function of N-methyl-D-aspartate receptor (NMDAr) is critical for the processes underlying learning, memory and synaptic plasticity. The hypofunction of NMDAr is currently the most accepted hypothesis for the pathophysiology of schizophrenia. This condition is induced in animal models using NMDA antagonist drugs, such as MK801, also known as Dizocilpine. Repeated injections during early postnatal days seem to be necessary to induce long-term structural brain changes and behaviors reminiscent of schizophrenia. Disturbances in glutamartergic transmission are especially relevant to mimic negative and cognitive symptoms of the disease. Schizophrenia is considered a neurodevelopmental disorder, although symptoms usually emerge during late adolescence/early adulthood, coinciding with GABAergic circuit maturation. It has been suggested that NMDA hypofunction preferentially affects GABAergic interneurons and perturbs the maturation of GABAergic circuits, including disrupted synaptic integration in early brain development and modified network activity and plasticity in adulthood. One of the most consistent findings is a downregulation of parvalbumin (PV) and glutamate descarboxylase 67 (GAD67) expressions in PV+ interneurons, which have been reliably reproduced in animal models of MK801. The modification in PV+ activity in prefrontal cortex and hippocampus generates a dyssynchrony in gamma oscillations, which are necessary for attention maintenance, working memory and executive functions in humans and rodents. One of the major challenges in schizophrenia research is trying to modify brain circuits that present long lasting aberrant synaptic wiring.

MARIAN M. DE PANCORBO is full Professor at the University of the Basque Country (UPV/EHU) since 2004. She is the Director of BIOMICs Research Group and the Coordinator of Lascaray Research Center of the UPV/EHU. She has published more than 150 papers in reputed journals and has organized the Service of Genetic Identification in the UPV/EHU.

DNA methylation is a key epigenetic mechanism that plays a crucial role in transcriptional regulation and controls several neurobiological and cognitive processes and has been shown to be involved in neurogenesis and brain development, neuronal activity, memory formation, drug addiction and neurodegeneration. In fact, neurological diseases have been associated with dysregulated DNA methylated profiles as well as with mutations in DNA methyltransferases 7 and methyl-CpG-binding proteins. Epigenomic landscapes are variable between cells and tissue types and, fluctuate in time according to a number of factors such as the age related, environmental or nutritional factors among others. The dynamism and tissue specificity of the epigenetic marks make specially challenging to design a successful epigenomic study, as opposed to the genomic studies of germline genetic variations, where the selection of tissue type or phenotyping of the sample is largely irrelevant. Thus, a key question for the current epigenetic studies concerns the degree to which easily accessible peripheral tissues (such as blood) can be used to ask questions about the epigenomic changes taking place in inaccessible tissues such as the brain. In the current study we have compared the methylation profiles in brain (cortex and hippocampus) and blood samples within the same individuals in order to create an inventory of epigenetic marks for which measurements in blood are informative for the brain tissue. The DNA methylation profiling of 13 matched cortex, hippocampus and whole blood samples was compared using the Illumina HumanMethylation27 DNA Analysis BeadChip assay.

Rosa María Hernandez obtained her PhD in Pharmacy at the Universidad de Salamanca in 1992. In 1993, Dr. Hernandez moved to University of the Basque Country (UPV/EHU) . Professor since 2009. She is Principal Investigator in several research projects and has supervised 16 PhD thesis works and co-authored more than 160 scientific articles and 10 patents. h-index: 32. Her research fields focus on several areas of drug delivery including micro- and nanoencapsulation of peptides and proteins as vaccine delivery systems, encapsulation of growth factors as an alternative therapy for Parkinson or Alzheimer’s diseases and cell based therapies for regenerative medicine.

Over the past years there has been a remarkable increase in the prevalence of neurodegenerative diseases (NDs). Clinically, NDs include chronically progressive dementias, ataxias and disorders of movement. The most common age-related NDs are Alzheimer’s and Parkinson’s diseases. Due to the low effectiveness of these treatments, promising and interesting therapies, such as growth factors (GFs), have been investigated. Nevertheless, the success of these new treatment options not only depends on the application of the specific neurotrophin, but also on a suitable approach for delivering these proteins to the brain. The development of appropriate drug delivery systems (DDS) may allow an enhancement of the GFs concentration in the brain, reaching therapeutic levels. In this sense, nanotechnologies could offer novel opportunities to formulate GFs using a wide variety of biodegradable nanocarriers, including polymeric nanospheres, lipidic nanocarriers, liposomes, and gene therapy, as possible treatments for the different neurodegenerative disorders.

Xavier Gironès is Director of Educational Innovation and Research at the Bages University Foundation (FUB), Universitat de Vic - Central University of Catalonia (UVic-UCC). PhD in Biology at the University of the Basque Country (UPV-EHU) and research assistant at the Institute for Research in Biomedical Sciences (IDIBAPS) at the Hospital Clinic Foundation. He has worked in various scientific and social projects related to stroke, Alzheimer's disease and other neurodegenerative diseases. His knowledge in neuroscience has led him to be the author in multiple papers and speaker at conferences both nationally and internationally. In this field he has excelled in the application of ICT solutions in neurodegenerative diseases.

At the present there is no unique explanation for the etiology of neurodegenerative diseases. Many of the explanations associate their appearance to many and different factors, both biological, environmental and genetic. Epidemiological data show that some chronic diseases act as risk factors in neurodegeneration. These include diabetes mellitus, hypertension, depression or obesity. The prevention of these chronic diseases could be reduced by 20% the prevalence of Alzheimer's. Also a reduction of only 25% in the prevalence of diabetes mellitus and hypertension, could reduce by 600,000 annual cases of Alzheimer's disease worldwide. In this collection of factors, also play an important role toxic habits, balanced diet, moderate physical activity or smoking. Given this variety of factors the prevention shown as the only viable strategy to combat the appearance and development of neurodegeneration. It is proposed as a more suitable strategy the control of cardiovascular parameters, such as cholesterol and triglycerides, and avoid high levels of oxidative stress, such as that caused by smoking or high levels of glucose in serum, due to advanced glycation end products. Furthermore there are protective factors that prove to be effective in reducing the prevalence of neurodegenerative diseases. The vast majority of these factors are also associated with the protection of the cardiovascular system, showing an association between them and the right brain health and delay aging. If the heart is protected, we protect the brain.

Elena Vecino completed her PhD at the University of Salamanca, Spain and a second PhD at the University of Lund (Sweden). She has researched in several European and American Universities. Full Professor of Cell Biology in 2014 at the University of Basque Country, directs the Experimental Ophthalmo-Biology Group (www.ehu.es/GOBE). She has published more tan 100 papers, directed 12 PhDs and has been member of National and International Agencies of evaluation research projects. She has been awarded by several institutions like the American Glaucoma Foundation, the ONCE, and recently has received the Alcon Foundation price for the excellence research in Glaucoma.

The retinal Müller glia, provide structural and trophic support to retinal ganglion cells (RGCs) in the healthy retina and may also have a function in promoting cell survival after injury. Defining and understanding glial heterogeneity is an important goal since it would enable to better understand the fundamental role of these cells during retinal pathologies. Their knowledge can open novel therapeutic avenues, such as targeted manipulations of sub-populations in order to quench pro-inflammatory destructive processes and/or stimulate regeneration of neurons in retinal degenerative eye diseases like glaucoma . Muller glia primary cell cultures in combination with RGCs have been studied. The heterogeneity of the glial cultures was characterized and their effect on RGC survival and neurite elongation. We found that cultured adult RGCs in close contact with adult Müller cells exhibit improved cell viability and significant neurite elongation. Not all Müller cells express their molecular markers with the same intensity. Moreover the condition media secreted by Müller glia neuro-protects the RGCs. These results suggest that Müller glia support RGC regeneration not only by direct interaction, but also releasing soluble trophic factors. Further understanding of the relationship between retinal glia and RGCs is important in order to identify potential therapeutic targets to encourage retinal neuroregeneration.

Juan Carlos Gomez graduated in medicine in 1992, and continued his training as a neurologist at the service of Neurology at University Hospital Cruces. He has completed his PhD from Department of Neurosciencience (UPV/EHU) and postdoctoral studies from New York Univestity (NYU). He is the director of Neurodegenerative Disease Group, Biocruces Research Institute. He has published more than 80 papers in reputed journals (Neurology, Lancet Neurology, Annals of Neurology, Movement Disoders, JNNP…). He has directed doctoral theses and has several international research projects. He has been funded by the Michael J Fox Foundation to conduct a study of biomarkers in Parkinson's disease.

In the last 10 years we have studied different mutations that cause Parkinson's disease or similar diseases. In 2004, our group described the third point mutation in the alpha-synuclein (SNCA) gene (G188A), which results in glutamic acid substitution by lysine in position 46 of the alpha-synuclein gene (E46K). The mutation was found in one large kindred with affected individuals spanning two generations. Alpha synuclein is a critical protein to the pathophysiology of PD. It is involved in the exocytosis of dopamine and other monoamines, and is present in Lewy bodies, the neuropathological characteristic finding in this disease. We have characterized the phenotype of this particular mutation, it shows severe parkinsonism and subsequent development of profound dementia and sleep disturbances that were present at early stages of the disease Our group is investigating disorders of the autonomic nervous system in these genotypes to better characterize different phenotypes, and to be extrapolated to other patients with idiopathic Parkinson's disease allowing us to define different subtypes of disease. The aim of our new research is to characterize E46K mutation carriers evaluating by MRI the integrity of the structure, microstructure and functional connectivity of the brain and the correlation of these findings with cognitive performance and visual disorders in family members at different clinical stages.

Gaizka Bilbao Barandika is Head of Section in the Department of Neurosurgery at Cruces Universitary Hospital. He is engaged in Movement Disorders Surgery among other areas. He has published some papers in this field. He got his thesis from the Basque Country University in 1995 and is at present Associate Professor of Neurosurgery in the same University.

Parkinson and Alzheimer diseases are the main and more frequent well-known neurodegenerative pathological entities. Both of them are responsible for a huge consumption of clinical, economic and social resources. Accordingly, a great effort is being made to get a disease-modifying therapy that alleviates that burden. Shortly, it could be defined as any intervention that favorably influences the underlying pathology or etiology, and thus, avoids a clinical decline. Among the current ways for treating Parkinson disease are levodopa, surgical approaches that target the subthalamic nucleus and a myriad of alternative medications. All of them have proved clinical benefit in patients. As far as Alzheimer disease is concerned, there is a dearth of treatments that put refrain, even in a very limited way, on the bleak ongoing development and progress of clinical deterioration. Lately, new surgical alternatives have been tried by stimulating certain areas of the brain (the forniceal area and the nucleus basalis Meynert) with promising results. What is worrying is that although a neuroprotective effect has been demonstrated by different agents and surgical procedures in vitro and in vivo in both diseases, there is not clinical evidence in patients. The way of lesioning, the imperfect animal models or the unknown etiology might explain the inconsistent results.