Pharmacological inhibition of mTORC1 reduces neural death and damage volume after MCAO by modulating microglial reactivity.

Autor: Villa-González M; Departamento de Biología (Fisiología Animal), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain., Rubio M; Physiopathology and Imaging of Neurological Disorders, Normandie University, UNICAEN, UMR-S U1237, INSERM, Institut Blood and Brain @ CaenNormandie, GIP Cyceron, Caen, France., Martín-López G; Departamento de Biología (Fisiología Animal), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain., Mallavibarrena PR; Departamento de Biología (Fisiología Animal), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain., Vallés-Saiz L; Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain., Vivien D; Physiopathology and Imaging of Neurological Disorders, Normandie University, UNICAEN, UMR-S U1237, INSERM, Institut Blood and Brain @ CaenNormandie, GIP Cyceron, Caen, France.; Department of Clinical Research, Caen-Normandie Hospital (CHU), Caen, France., Wandosell F; Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain. fwandosell@cbm.csic.es.; Centro de Investigaciones Biológicas en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. fwandosell@cbm.csic.es., Pérez-Álvarez MJ; Departamento de Biología (Fisiología Animal), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain. mj.perez@uam.es.; Instituto Universitario de Biología Molecular (IUBM-UAM), Madrid, Spain. mj.perez@uam.es.
Jazyk: angličtina
Zdroj: Biology direct [Biol Direct] 2024 Apr 06; Vol. 19 (1), pp. 26. Date of Electronic Publication: 2024 Apr 06.
DOI: 10.1186/s13062-024-00470-5
Abstrakt: Ischemic stroke is a sudden and acute disease characterized by neuronal death, increment of reactive gliosis (reactive microglia and astrocytes), and a severe inflammatory process. Neuroinflammation is an early event after cerebral ischemia, with microglia playing a leading role. Reactive microglia involve functional and morphological changes that drive a wide variety of phenotypes. In this context, deciphering the molecular mechanisms underlying such reactive microglial is essential to devise strategies to protect neurons and maintain certain brain functions affected by early neuroinflammation after ischemia. Here, we studied the role of mammalian target of rapamycin (mTOR) activity in the microglial response using a murine model of cerebral ischemia in the acute phase. We also determined the therapeutic relevance of the pharmacological administration of rapamycin, a mTOR inhibitor, before and after ischemic injury. Our data show that rapamycin, administered before or after brain ischemia induction, reduced the volume of brain damage and neuronal loss by attenuating the microglial response. Therefore, our findings indicate that the pharmacological inhibition of mTORC1 in the acute phase of ischemia may provide an alternative strategy to reduce neuronal damage through attenuation of the associated neuroinflammation.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje