Ischemic stroke is devastating, with serious long-term disabilities affecting millions of people worldwide. Growing evidence has shown that mesenchymal stem cells (MSCs) administration after
stroke provides neuroprotection and enhances the quality of life in
stroke patients. Previous studies from our lab have shown that 1 × 105 MSCs administered intra-arterially (IA) at 6 h post
stroke provide neuroprotection through the modulation of
inflammasome and
calcineurin signaling.
Ischemic stroke induces endoplasmic reticulum (ER) stress, which exacerbates the pathology. The current study intends to understand the involvement of
brain-derived neurotrophic factor/
tropomyosin receptor
kinase B (
BDNF/TrkB) signaling in preventing apoptosis induced by ER stress post
stroke following IA MSCs administration.
Ischemic stroke was induced in ovariectomized female Sprague Dawley rats. The MSCs were administered IA, and animals were sacrificed at 24 h post
stroke.
Infarct area, neurological deficit score, motor coordination, and biochemical parameters were evaluated. The expression of various genes and
proteins was assessed. An inhibition study was also carried out to confirm the involvement of
BDNF/TrkB signaling in ER stress-induced apoptosis. IA-administered MSCs improved functional outcomes, reduced
infarct area, increased neuronal survival, and normalized biochemical parameters.
mRNA and
protein expression of ER stress markers were reduced, while those of
BDNF and TrkB were increased. Reduction in ER stress-mediated apoptosis was also observed. The present study shows that IA MSCs administration post
stroke provides neuroprotection and can modulate ER stress-mediated apoptosis via the
BDNF/TrkB signaling pathway.