LaNCE Research Group is based at the Department of Neuroscience of the University of the Basque Country (UPV/EHU). The group is composed by Basic and Clinical researchers belonging to several Departments of the University ensuring a traslational approach to Neuroscience:

  • Department of Neuroscience
  • Department of Surgery

Our main research topic is brain vasculature, focused on anatomical organisation, morphological substrate of main function and pathological changes in disorders such as tumours, traumatic brain injuries or haemorrhages. The focus of our research is microvasculature, territory where metabolic interchanges between blood and parenchyma are done and the molecules that regulate the neurogliovascular unit, that we have termed as angioglioneurins, with VEGF as the key role player. Microvascular networks is also the level where modifications due to plascitity are done in order to adapt to new conditions, such as neoangiogenesis, oedema origin and reabsorption, formation of microtrombi. The development of the cortical microvascular network is resumed in this video

Our research interests share thus experimental and clinical aims.

Our main research topics are:

1. Postnatal development of Brain Vascularization and Blood Brain Barrier

WeI reported a decrease of the vascular density in dark reared animals and a retard in the maturation of the vascular pattern. The next step was the immunohistochemical distribution of VEGF and its receptors in animals reared in several conditions including animals reared in complex visual environments combined with the role played by VEGF in other pathological situations as the Traumatic Brain Injury, performed in a model of cortical micronecrosis by UV irradiation.
At this moment we are working on the Biochemical quantification of the VEGF along the postnatal development of the different experimental groups and the effects of the intracortical administration and inhibition of the VEGF by osmotic minipumps on immunohistochemical distribution and Biochemical levels.
Another point of our current interest is the role played by physical exercise in enriched environments and its potentially useful therapeutical effects in several experimental injuries.

2. Identification analysis and validation of clinical, biological and molecular markers to improve prognosis in brain tumours.

Apart from the physiological role of the VEGF on the postnatal development of the cortex, pathological angiogenesis occur in pathologies such as brain tumours. High grade gliomas are the most common primary brain tumours and are the most vascularized ones, as their growth and survival depends on a constant vascular remodelling.
The aim of this research line is to identify and validate clinical and biological indicators statistically significant to ameliorate the diagnosis, treatment and prognosis of patients with brain tumours, being angiogenic cytokines one of them, as they participate not only in the progression of the tumour, but also in the progression of the oedema, which is one of the main clinical complications.
Cases and material from tumour banks are used and a phenotypic and genotypic characterisation is also performed, including the comprehension and even prognosis of the patient clinical course. Our work also include studies on the peculiar tumoral microenvironment, fundamental to understand many of the limitations of most treatments and field of new therapeutic strategies. For this purpose we analyse the antigenic profile by antibody arrays correlating them with DNA arrays and tissue arrays. As previously related, most of the studied molecules are involved in the angiogenic switch characteristic of gliomas.

3. Microvascularization of brain tumours and its environment. Regulation of angiogenesis

Brain gliomas are characterised by their aggressivity and vascularization. We have developed a model of transplacentary induction of gliomas in rats by Ethyl Nitrosurea administration. This model reproduces glial tumours similar to human ones where we analyse the progression of the tumour as well as the microvascular changes and the interphase tumoral/normal tissue. Firstly we identified  histopathologically the experimental gliomas and now we are performing the molecular characterisation of theses tumours and their relationship with the BBB permeability. For this purpose we locate and evaluate tumours in vivo by MRI. The analysis of implied molecules is done by the use of antibody and c-DNA matrices as well as immunohistochemistry and biochemistry (EIA and Western Blot). The aim is to find evidences of the regulation of the angiogenic switch and the permeability of the BBB, both are necessary to design antiangiogenic strategies and to develop a controlled permeability of the BBB to allow the passage of drugs to the CNS.

4. Combination of Neuroprotective strategies in Traumatic injuries in the developing brain.

Despite the general belief that the young brain is more resilient to injury than the adult brain, lesions at early ages often produce more severe effects than equivalent lesions in adults, or evolve in a completely different way. Clinical experience suggests that injury to the immature brain can result in abnormal development and long-standing neurobehavioral impairment, even if there is little evidence of morphological damage.
Our interest is focused on the combination of neuroprotective and neurorescue factors such as enriched environment, physical exercise and VEGF to find the better synergic strategy. The combination of an enriched environment and VEGF infusion shows a better recovery of the tissue surrounding the lesion. An enriched environment has been proposed for treatment of several types of brain damage because among other effects, its angiogenic and anti-apoptotic effects could tip the balance for the insulted cells in the transitional penumbra area towards survival instead of towards death.
Another fact that could contribute to neuroprotection is the acceleration of cortical maturation induced by an EE. A higher degree of maturation could diminish the spread of brain edema, minimizing the consequences of the injury.
Our work include stereological, morphological and neurobehavioral studies to achieve the results of the different proposed strategies.

Research team:

Jose Vicente Lafuente. PhD.  Head of the Group. Professor of Anatomy

Susana Bulnes. PhD. Lecturer of Anatomy

Harkaitz Bengoetxea. PhD. Assistant Professor of Anatomy

Naiara Ortuzar. PhD. Assistant Professor of Anatomy

Catalina Requejo. PhD. Postdoctoral Fellow

Hodei Cepeda. Master in Neuroscience. Predoctoral Fellow

Ane Murueta-Goyena. Master in Neuroscience. Predoctoral Fellow

Iñigo Pomposo. PhD. Neurosurgeon. Lecturer of Surgery

Alex Carrasco. PhD. Neurosurgeon. Lecturer of Surgery

 

 

Repository

Here is located the repository of the papers published by LaNCE