Protective Effects of Adipose-derived Stem Cell Exosomes vs Dexamethasone on Neuromotor Deficits in Focal Cerebral...

Cerebral ischemia is a leading cause of mortality and long-term disability worldwide, characterized by restricted blood flow to the brain, resulting in inflammation, oxidative stress, and neuronal death. Current therapies, such as thrombolytics and corticosteroids, offer limited efficacy in reversing neuronal damage. Recent advances suggest that exosomes derived from mesenchymal stem cells (MSCs) may provide neuroprotective benefits through anti-inflammatory and regenerative mechanisms. This study aimed to evaluate the therapeutic effects of exosomes derived from adipose tissue-MSCs (AT-MSCs) compared to dexamethasone in a rat model of transient focal cerebral ischemia.

Twenty adult male Wistar rats were randomly assigned to four groups: Sham, transient middle cerebral artery occlusion (MCAO) control, exosome-treated, and dexamethasone-treated. MACO was induced to simulate an ischemic stroke. Exosomes were administered intravenously, while dexamethasone was given intraperitoneally. Behavioral assessments (Bederson and Garcia scores), infarct volume (2,3,5-triphenyltetrazolium chloride [TTC] staining), serum inflammatory markers (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]), and histopathological changes (H&E and Nissl staining) were analyzed.

Exosome treatment significantly improved neurological function and motor performance compared to the MCAO group, with superior outcomes relative to dexamethasone. Exosomes markedly reduced infarct volume and inflammatory biomarker levels, and histological analyses revealed preserved neuronal structure and reduced necrosis. Nissl staining revealed a higher count of healthy neurons in the exosome group compared to the other treatment groups.

Exosomes derived from AT-MSCs offer superior neuroprotective effects in ischemic brain injury compared to dexamethasone. Their multi-modal mechanisms-including anti-inflammatory, anti-apoptotic, angiogenic, and neuroregenerative effects-highlight their potential as a novel therapeutic approach for stroke management. Future research should focus on clinical translation, dosage optimization, and long-term safety evaluation.