Preclinical models of stroke in aged animals with or without comorbidities: role of neuroinflammation.
Age is the principal nonmodifiable risk factor for stroke. Over the past 10 years, suitable models for stroke in aged rats have been established. At genetic and cellular level there are significant differences in behavioral, cytological and genomics responses to injury in old animals as compared with the young ones. Behaviorally, the aged rats have the capacity to recover after cortical infarcts albeit to a lower extent than the younger counterparts. Similarly, the increased vulnerability of the aged brain to stroke, together with a decreased interhemisphere synchrony after stroke, assessed by different experimental methods (MRI, fMRI, in vivo microscopy, EEG) leads to unfavorable recovery of physical and cognitive functions in aged people and may have a prognostic value for the recovery of stroke patients. Furthermore, in elderly, comorbidities like diabetes or arterial hypertension are associated with higher risk of stroke, increased mortality and disability, and poorer functional status and quality of life. Aging brain reacts strongly to ischemia-reperfusion injury with an early inflammatory response. The process of cellular senescence can be an important additional contributor to chronic post-stroke by creating a "primed" inflammatory environment in the brain. Overall, these pro-inflammatory reactions promote early scar formation associated with tissue fibrosis and reduce functional recovery. A better understanding of molecular factors and signaling pathways underlying the contribution of comorbidities to stroke-induced pathological sequelae, may be translated into successful treatment or prevention therapies for age-associated diseases which would improve lifespan and quality of life.
Department of Functional Sciences, Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy, Craiova, Craiova, Romania.
A-M
AM
Buga
Mario
M
Di Napoli
A
A
Popa-Wagner
D000367:Age Factors; D000375:Aging; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D015897:Comorbidity; D004195:Disease Models, Animal; D006801:Humans; D009443:Neuritis / Q000150:complications* / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D011379:Prognosis; D020127:Recovery of Function; D012307:Risk Factors; D020521:Stroke / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000523:psychology