​<EM>BLOOD CELL–DERIVED SECRETOME AS A NEUROPROTECTIVE STRATEGY IN COMORBIDITY-RELEVANT MODELS OF ISCHEMIC STROKE</EM>

The blood cell–derived secretome (Sec) from healthy donors represents a promising therapeutic strategy that mediates systemic protective effects. This approach may remain effective even in patients with comorbidities, including advanced age and conditions associated with increased systemic inflammation, where conditioning-based interventions are less effective. The therapeutic effects of Sec derived from young, healthy donors were evaluated in two clinically relevant models of ischemic injury induced by Middle Cerebral Artery Occlusion (MCAO). In aged 13-month-old rats, groups included MCAO and MCAO+Sec. In the lipopolysaccharide (LPS)-induced systemic inflammation model, groups included MCAO, LPS+MCAO, and LPS+MCAO+Sec. Outcomes were evaluated using complementary functional (neurological scoring), histological (FluoroJade labeling), and biochemical (TTC staining and comet assay) measures of neuroprotection. Sec treatment significantly reduced neurological deficit scores in both aged and LPS models. Infarct size was also significantly reduced in Sec-treated groups compared with MCAO controls in both models. FluoroJade-positive cells were significantly lower in the cortex and striatum penumbra in the LPS model. At the same time, a trend toward reduction was observed in the striatum penumbra of aged rats, though not statistically significant. Comet assay revealed a marked reduction in oxidative stress in Sec-treated LPS rats, whereas aged rats showed a modest, non-significant decrease. These findings demonstrate that Sec confers robust neuroprotection under conditions of aging and systemic inflammation, highlighting its potential as a translatable therapeutic strategy. Future studies should explore its mechanistic pathways and broader applicability for mitigating ischemic brain injury in comorbid populations.
Supported by APVV 21-0069 and VEGA 2/0037/25.