Fisiopatología Neurovascular

The interest of our group is cerebrovascular disease, one of the leading causes of death and disability, with an increasing prevalence due to the ageing of the population. Specifically, our major focus is the investigation of stroke and vascular cognitive impairment, among the most devastating disorders and a major socio-economic problem for societies and health-care systems worldwide because of their enormous costs.

Stroke is caused by the interruption of the blood supply to the brain: most strokes (87%) are ischaemic (caused by thrombosis or embolisms) and the rest are haemorrhagic (caused mainly by rupture of blood vessel or aneurysm). By cutting off the supply of oxygen and nutrients, stroke causes damage to the brain tissue: the effects depend on which part of the brain is injured and how severely it is affected. A very severe stroke can cause sudden death. But stroke is more incapacitating than lethal: it is the major cause of neurological disability and the second cause of dementia after Alzheimer's disease (AD).

Dementia is one of the most common ageing-associated disorders. In particular, vascular dementia (VD) refers to brain disorders where cognitive decline is of cardiovascular basis. Nowadays, the term vascular cognitive impairment (VCI) is preferred to better reflect the full range of cognitive syndromes resulting from cerebrovascular disease, from the clinically well-defined stroke to subclinical cerebrovascular injuries, where VD would be the most severe expression. Cerebrovascular disease is also as an adjuvant for the expression of dementia caused by other factors, including AD and other neurodegenerative diseases; in fact, mixed forms of the disease (VD/AD) are now believed to be much more common than the “pure” ones. Pathogenic mechanisms and, therefore, resulting neuropathologies vary for each VCI subtype, a fact not sufficiently considered in this area of research.

In this context, our group studies key questions in stroke and VCI by applying different models and novel technologies, with the final aim to translate findings to patients. Our laboratory has established relevant paradigms of ischemic and hemorrhagic stroke, of post-stroke dementia, as well as of VCI induced by carotid stenosis-induced hypoperfusion and by high-sodium-induced pre-hypertension. In acute stroke, we have contributed to the clarification of the actions of several receptors/molecules (Cuartero et al, Circulation 2014) as well as to the elucidation of mechanisms of central and systemic inflammation and immunothrombosis (Garcia-Culebras et al., Stroke 2019; Peña-Martinez et al. Stroke 2019), and excitotoxicity (Mallolas et al., JEM 2006; Godino et al., JCI 2013), among others. We have characterized maladaptive neurogenesis and the development of aberrant hippocampal circuitry as major mechanisms of VCI (Cuartero et al., JCI 2019). We are also interested in neuroimaging as a tool for the identification of non-invasive, differential biomarkers of VCI subtypes.