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The mesenchymal stem cells (MSCs)-derived exosomes hold a promise for addressing neurodegeneration-associated neurological disorders owing to their distinctive immunomodulatory and regenerative properties. The investigation explored the therapeutic potential of MSCs-derived exosomes to mitigate the pathological changes in the cerebellar cortex in a rat model of PD. Thirty rats were divided into control, PD, and PD-BM-MSCs-derived exosomes groups. For 5 weeks, rodents were administered a subcutaneous injection of 2\u2005mg\/kg\/day of rotenone to induce a PD model. The PD group exhibited a substantial increase in relative cerebellar mRNA HOTAIR, BAX, and caspase 3 gene expression, along with a concomitant decrease in relative cerebellar miRNA-221 gene expression. Light and transmission electron microscopy also depicted marked degenerative changes in the cerebellar cortex. The immune expression of glial fibrillary acidic protein and ionized calcium-binding adaptor molecule-1 markedly increased, while synaptophysin expression markedly decreased. Interestingly, all changes showed a significant regression following treatment with exosomes derived from BM-MSCs. In conclusion, BM-MSCs-derived exosomes may be a promising PD intervention strategy.<\/jats:p>","DOI":"10.1093\/mam\/ozaf062","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T07:42:13Z","timestamp":1750750933000},"source":"Crossref","is-referenced-by-count":2,"title":["Ameliorative Potential of Mesenchymal Stem Cells-derived Exosomes on the Cerebellar Cortex in a Rat Model of Parkinson's Disease: Targeting HOTAIR\/miRNA-221 Signaling Axis: A Histological, Immunohistochemical, and Biochemical Study"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5233-1990","authenticated-orcid":false,"given":"Amany Mohamed","family":"Shalaby","sequence":"first","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine, Tanta University , Tanta 31527 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