Línies de recerca

  • Blood-brain barrier disruption in cerebrovascular diseases

    Blood-brain barrier (BBB) disruption is one of the major deleterious mechanisms implicated in the physiopathology of Central Nervous System diseases. In experimental models the BBB is rapidly disrupted after acute ischemic stroke or subarachnoid hemorrhage onset, persists for days through the acute and early subacute phases and contributes to poor outcomes. However, the clinical relevance and mediators of early BBB disruption in these diseases are poorly understood. We aim to evaluate the dynamics, prognostic relevance and underlying mechanisms of BBB disruption through a translational approach, with special focus in the deleterious role of oxidative stress and in the diagnostic yield of advanced neuroimaging techniques.

  • Brain-gut cross-talk in stroke: targeting gut barrier dysfunction and immune responses to improve stroke outcome

    Infection is a frequent complication of stroke associated with mortality and poor neurological recovery. Recent experimental studies show that post-stroke infection results from translocation of gut commensal microbiota, which results in the activation of immune cells that reach the brain after stroke promoting neuroinflammation. In this project, we explore whether bacterial translocation in the gut explains stroke-associated infections in patients with ischemic and hemorrhagic stroke and we will measure the capacity of peripheral blood mononuclear cell to alter the expression of genes involved in gut barrier function. We expect that understanding the mechanisms underlying gut barrier dysfunction, bacterial translocation, and subsequent immune cell activation, will help develop treatments to reduce the deleterious consequences of infections and immunity on the brain lesion.

  • Inflammatory and immune responses to stroke

    Brain cell death after acute stroke triggers inflammation, involving glial and endothelial cell activation, invasion of leukocytes to the damaged tissue and peripheral reactions. Several lines of evidence support that excessive inflammation exacerbates brain damage but it is becoming apparent that certain aspects of the inflammatory response are necessary to set processes later involved in tissue repair. We investigate the contribution of inflammatory and innate immune responses to stroke brain damage. We have different lines of research particularly focusing on various immune cellular players including the brain resident microglia and perivascular macrophages, and neutrophils, monocytes/macrophages, and dendritic cells. We study the modulation of these responses as potential therapeutic interventions to improve stroke outcome.

  • The chemical optimization of cerebral embolectomy

    Mechanical thrombectomy (MT) increases brain reperfusion and the likelihood of good outcome in patients with acute stroke but only about one third obtain complete brain reperfusion. We aim to evaluate whether rescue intraarterial (IA) thrombolysis following MT improves the rate of complete brain reperfusion and outcome in selected patients with acute stroke. The expected results of our study could modify the current therapeutic guidelines used worldwide to treat these patients.

  • Therapeutic use of uric acid as peroxynitrite scavenger in acute ischemic stroke

    Studies at our lab have identified the value of uric acid administration after a brain embolism and how it acts in synergy with reperfusion therapies to neuroprotect the ischemic brain. We aim to consolidate these findings and unravel the mechanisms involved. We have provided strong signals of the efficacy of uric acid administrtation in patients with acute stroke and our major goal for these years is to validate this approach in confirmatory trials that might lead to its regulatory approval.    

  • Vascular changes with aging and in animal models of vascular dementia

    Vascular dementia (VaD) is recognized as one of the leading causes of cognitive impairment and dementia in the elderly, and has become one of the most common causes of morbidity. It is critical to implement new ways of addressing VaD with new experimental designs, and new tools that facilitate its study in all stages, and to provide accurate and early diagnosis. Based on this premise, we incorporate different risk factors such as age, atherosclerosis, and hypertension, amongst others, in the study of brain lesions in gray matter and white matter caused by chronic hypoperfusion in murine models of VaD.