miR-9-5p is Downregulated in Serum Extracellular Vesicles of Patients Treated with Biperiden After Traumatic Brain Injury

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Villena-Rueda, Beatriz Enguidanos ; Kajitani, Gustavo Satoru ; Ota, Vanessa Kiyomi ; Honorato-Mauer, Jessica ; Santoro, Marcos Leite ; Bugiga, Amanda Victoria Gomes ; Rosa, Joice Santos ; Asprino, Paula Fontes ; Meneghetti, Paula ; Torrecilhas, Ana Claudia ; Intasqui, Paula ; Bertolla, Ricardo Pimenta ; Foresti, Maira Licia ; Naffah-Mazzacoratti, Maria da Graca ; Mello, Luiz Eugenio Araujo de Moraes ; Belangero, Sintia Iole

• Tipo de documento: Artigo Científico
• Fonte: Molecular Neurobiology; v. 61, n. 11, p. 13-pg., 2024-04-26.

Resumo

Traumatic brain injury (TBI) is a prevalent and debilitating condition, which often leads to the development of post-traumatic epilepsy (PTE), a condition that yet lacks preventive strategies. Biperiden, an anticholinergic drug, is a promising candidate that has shown efficacy in murine models of PTE. MicroRNAs (miRNAs), small regulatory RNAs, can help in understanding the biological basis of PTE and act as TBI- and PTE-relevant biomarkers that can be detected peripherally, as they are present in extracellular vesicles (EVs) that cross the blood-brain barrier. This study aimed to investigate miRNAs in serum EVs from patients with TBI, and their association with biperiden treatment and PTE. Blood samples of 37 TBI patients were collected 10 days after trauma and treatment initiation in a double-blind clinical trial. A total of 18 patients received biperiden, with three subjects developing PTE, and 19 received placebo, with two developing PTE. Serum EVs were characterized by size distribution and protein profiling, followed by high-throughput sequencing of the EV miRNome. Differential expression analysis revealed no significant differences in miRNA expression between TBI patients with and without PTE. Interestingly, miR-9-5p displayed decreased expression in biperiden-treated patients compared to the placebo group. This miRNA regulates genes enriched in stress response pathways, including axonogenesis and neuronal death, relevant to both PTE and TBI. These findings indicate that biperiden may alter miR-9-5p expression in serum EVs, which may play a role in TBI resolution. (AU)

• Processo FAPESP: 23/04184-0 - Busca por miRNAs provenientes de vesículas extracelulares relevantes para a epileptogênese e escore poligênico de risco de pacientes que sofreram traumatismo cranioencefálico
• Beneficiário: Beatriz Enguidanos Villena Rueda
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 22/14055-0 - Avaliação do potencial prognóstico de MicroRNAs no desenvolvimento de epilepsia pós trauma cranioencefálico
• Beneficiário: Gustavo Satoru Kajitani
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/24561-5 - Epileptogênese, biomarcadores e epilepsia pós-traumática
• Beneficiário: Luiz Eugenio Araujo de Moraes Mello
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 21/14564-0 - Busca por miRNAs provenientes de exossomos relevantes para a epileptogênese
• Beneficiário: Beatriz Enguidanos Villena Rueda
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica