RG8: Stroke and Neuroprotection
Stroke is the first cause of death and disability in Portugal and the second in Europe, being associated with enormous social and economic burden. Ischemic stroke results from the lack of blood supply (ischemia) caused by thrombosis or embolism. Cerebral ischemia causes calcium overload, excitotoxicity, oxidative stress, excessive neuroinflammation and ultimately neural cell death.
Main focus: cerebrovascular diseases like stroke, dementia, vascular dementia, and age-related white matter changes.
Main research lines:
- Enhancement of endogenous mechanisms of defense. (Pre)conditioning or hormesis induction consists of an insult that does not cause damage but triggers a protective state (tolerance) that activates endogenous mechanisms of defense. Thus, the first research line is pre-clinical and concerns the use of the endogenous carbon monoxide molecule in the modulation of brain cell metabolism and glia-neuron communication to promote cytoprotection.
- The second is a translational research strategy based on remote ischemic conditioning for stimulating endogenous mechanisms of defense. Both approaches target protection of brain parenchyma against excessive neuroinflammation and cell death.
- Finally, the third research line is clinical and concerns both acute stroke treatment and secondary prevention. Age-related white matter lesions of presumed vascular etiology have also been the focus of our attention. Age associated cognitive and motor impairment, including Alzheimer disease and Parkinson disease are studied in collaboration with RG9: Neurophysiology and Degeneration.
- To understand the underlying molecular mechanisms of ischemia and reperfusion in brain parenchyma;
- To identify novel circulating biomarkers for stroke with diagnostic and prognostic value;
- To contribute to acute stroke treatment and secondary prevention.
Keywords: Stroke; Ischemia; Hypoxia; Dementia; Neuroprotection
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Dias-Pedroso D, Guerra J, Gomes A, Oudot C, Brenner C, Santos CN, Vieira HLA (2019) Phenolic metabolites modulate cardiomyocyte beating in response to isoproterenol. Cardiovascular Toxicology 19(2):156-167
Almeida AS, Soares NL, Sequeira CO, Pereira SA, Sonnewald U, Vieira HLA (2018) Improvement of neuronal differentiation by carbon monoxide: role of pentose phosphate pathway. Redox Biology 17:338-347
Dreyer-Andersen N, Almeida AS, Jensen P, Kamand M. Okarmus J, Rosenberg T, Friis SD, Martínez Serrano A, Blaabjerg M, Kristensen BW, Skrydstrup T, Gramsbergen JB, Vieira HLA, Meyer M (2018) Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells. PlosONE 13(1):e0191207
Santos CN, Gomes A, Oudot C, Dias-Pedroso D, Rodriguez-Mateos A, Vieira HLA, Brenner C (2018) Pure polyphenols applications for cardiac health and disease. Current Pharmaceutical Design (in press)