Brain Pericytes Acquire Stemness via the Nrf2-Dependent Antioxidant System

Area of Science:

• Neuroscience
• Stem Cell Biology
• Regenerative Medicine

Background:

• Pericytes (PCs) are crucial support cells in capillaries.
• Recent evidence suggests PCs possess multipotent stem cell characteristics and contribute to tissue repair.
• The transformation of normal brain pericytes (nPCs) into ischemic pericytes (iPCs) following stroke is an area requiring further investigation.

Purpose of the Study:

• To compare the characteristics of normal brain pericytes (nPCs) and ischemic pericytes (iPCs).
• To investigate the role of oxidative stress and the Nrf2 pathway in pericyte reprogramming after ischemic stroke.

Main Methods:

• Isolation and characterization of nPCs and iPCs from a mouse stroke model.
• Assessment of reactive oxygen species and Nrf2 levels.
• Induction of Nrf2 pathway activation using oxygen-glucose deprivation/reoxygenation and tBHQ treatment.
• Analysis of stem cell marker expression (nestin, Sox2, CDH1) and neuronal differentiation.

Main Results:

• nPCs and iPCs share common pericytic markers.
• iPCs exhibit higher levels of reactive oxygen species and nuclear Nrf2 accumulation compared to nPCs.
• Nrf2 activation (via OGD/reoxygenation or tBHQ) increases nestin levels in nPCs.
• Overexpression of Nrf2 in PCs promotes epithelial marker expression and the formation of neurosphere-like clusters that differentiate into neurons.

Conclusions:

• Oxidative stress and the Nrf2 pathway are essential for converting pericytes into stem cells post-stroke.
• These findings highlight the potential of targeting the Nrf2 pathway for novel therapeutic strategies in ischemic stroke treatment.