Journal Article

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

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

2024

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Adult / Animal models / Anticholinergics / Axonogenesis / Biomedical and Life Sciences / Biomedicine / Blood-brain barrier / Brain Injuries, Traumatic - blood / Brain Injuries, Traumatic - drug therapy / Brain Injuries, Traumatic - genetics / Cell Biology / Cellular stress response / Chromosome 5 / Clinical trials / Double-Blind Method / Down-Regulation - drug effects / Down-Regulation - genetics / Epilepsy / Epilepsy, Post-Traumatic - blood / Extracellular vesicles / Extracellular Vesicles - metabolism / Female / Humans / Male / MicroRNAs / MicroRNAs - blood / MicroRNAs - genetics / MicroRNAs - metabolism / Middle Aged / miRNA / Neurobiology / Neurology / Neurosciences / Next-generation sequencing / Patients / Placebos / Size distribution / Traumatic brain injury / Young Adult