Aurora Semerano, MD
Wang C, Börger V, Mohamud Yusuf A, Tertel T, Stambouli O, Murke F, Freund N, Kleinschnitz C, Herz J, Gunzer M, et al. Postischemic Neuroprotection Associated With Anti-Inflammatory Effects by Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles in Aged Mice. Stroke. 2022;53:e14–e18.
Age is the most important non-modifiable stroke risk factor. Over 80% of ischemic strokes occur in people aged 65 years and older. Elderly patients with stroke have higher mortality, greater disability, and longer hospitalizations, they receive less evidence-based care, and they are less likely to be discharged to their original place of residence.1 Understanding the mechanisms of increased vulnerability that occurs with age is pivotal to reveal new therapeutic opportunities for stroke.
A profound dysregulation of the immune system is observed in elderly people, and it is commonly referred to with the term “inflamm-ageing”,2 characterized by a persistent subtle increase of inflammatory stress accompanied by a blunted inflammatory response to immunogenic triggers. “Inflamm-ageing” likely contributes to the pathophysiology of different age-dependent conditions, including stroke. Patients with ischemic stroke showed increased plasma levels of the pro-inflammatory cytokine TNF-α with age.3 A transcriptomic analysis of peripheral blood RNA in patients with acute ischemic stroke revealed differential expression in aged and young patients, mostly in genes associated with altered B-cell receptor signaling, lymphocyte proliferation, and leukocyte homeostasis.4 In human postmortem brain tissue, age positively correlates with neutrophil infiltration, MMP-9 expression, and hemorrhagic transformation.5 However, studying ageing and its consequences in humans is tricky as other cerebrovascular risk factors can operate as confounders. In this context, experimental stroke in rodents offers the advantage to isolate the effects of ageing. TNF-α inhibition restored the volume of cerebral infarct, neuromotor performance, and survival rates in aged stroke mice to the levels observed in young ones.3 After middle cerebral artery occlusion (MCAO), aged animals reconstituted with young bone marrow showed reduced behavioral deficits and significantly fewer brain-infiltrating neutrophils compared to younger controls.5