MicroRNA-199a-5p attenuates blood-brain barrier disruption following ischemic stroke by regulating PI3K/Akt signaling

Guangxiao Ni1, Lulu Kou1, Chunqiao Duan1

  • 1Department of Rehabilitation of the Second Hospital of Hebei Medical University, Shijiazhuang, China.

Plos One
|September 20, 2024
PubMed
Abstract

Insights

MicroRNA-199a-5p (miR-199a-5p) mimic improved neurological function and reduced blood-brain barrier (BBB) disruption after ischemic stroke in rats by activating the PI3K/Akt pathway.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Ischemic stroke poses a significant threat to brain health, often leading to blood-brain barrier (BBB) disruption.
  • MicroRNAs (miRNAs) are emerging as key regulators in post-stroke recovery and BBB integrity.
  • Understanding the role of specific miRNAs like miR-199a-5p in stroke pathophysiology is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the regulatory role of miR-199a-5p in maintaining blood-brain barrier (BBB) integrity following ischemic stroke.
  • To elucidate the involvement of the PI3K/Akt signaling pathway in miR-199a-5p-mediated effects on BBB integrity.

Main Methods:

  • Adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO) to induce ischemic stroke.
  • Neurological function was assessed using the Ludmila Belayev 12-point scoring system.
  • Blood-brain barrier integrity was evaluated using Evans Blue staining, immunofluorescence, western blotting, and RT-PCR.

Main Results:

  • miR-199a-5p mimic treatment enhanced motor activity and proprioception in MCAO rats.
  • miR-199a-5p mimic reduced PIK3R2 expression, activated the PI3K/Akt pathway, and increased Claudin-5 and VEGF expression in the ischemic penumbra.
  • Treatment with miR-199a-5p mimic alleviated inflammation, decreased BBB leakage, and reduced neurocyte apoptosis.

Conclusions:

  • MiR-199a-5p mimic plays a protective role in ischemic stroke by modulating the PI3K/Akt pathway.
  • This miRNA intervention attenuated BBB disruption and reduced inflammatory responses post-stroke.
  • miR-199a-5p represents a potential therapeutic target for mitigating stroke-induced brain damage.