Apelin-13/APJ promotes neural stem cells to repair ischemic stroke

Area of Science:

• Neuroscience
• Regenerative Medicine
• Pharmacology

Background:

• Neural stem cell (NSC) therapy shows promise for ischemic stroke but is limited by the harsh ischemic and hypoxic brain environment.
• Drug stimulation strategies are being explored to enhance NSC therapeutic efficacy in ischemic stroke models.

Purpose of the Study:

• To investigate the potential of the small molecule peptide Apelin-13 to improve NSC function under simulated ischemic conditions.
• To elucidate the mechanisms by which Apelin-13 affects NSC viability, migration, apoptosis, and neurotrophic factor expression.

Main Methods:

• Neural stem cells were subjected to oxygen-glucose deprivation (OGD) to mimic ischemic conditions.
• The effects of Apelin-13 treatment on NSC viability, migration, and apoptosis were assessed.
• Expression levels of brain-derived neurotrophic factor (BDNF) were measured.
• The role of the Apelin-13 receptor, APJ, was investigated using knockdown experiments.

Main Results:

• Apelin-13 (100 nM) mitigated OGD-induced suppression of NSC viability and enhanced NSC migration under OGD.
• Apelin-13 reduced OGD-induced NSC apoptosis and modulated the Bcl-2 to Bax ratio.
• Apelin-13 further increased BDNF expression in NSCs under OGD conditions.
• Knockdown of the APJ receptor abolished the beneficial effects of Apelin-13 on NSCs and BDNF expression during OGD.

Conclusions:

• Apelin-13 significantly enhances NSC viability, migration, and survival while reducing apoptosis under OGD conditions, mediated through the APJ receptor.
• The Apelin-13/APJ system, potentially via downstream BDNF, represents a promising therapeutic strategy to improve NSC-based treatments for ischemic stroke.
• Targeting the Apelin-13/APJ pathway could activate endogenous NSCs for treating ischemic stroke.