Rapamycin Treatment Reduces Brain Pericyte Constriction in Ischemic Stroke

Area of Science:

• Neuroscience
• Vascular Biology
• Pharmacology

Background:

• Brain pericyte contraction and death contribute to microvascular no-reflow after ischemic stroke.
• Mammalian target of rapamycin (mTOR) inhibition reduces cancer cell motility and neuronal death in stroke.
• The effect of mTOR inhibition on brain pericytes during ischemia is unknown.

Purpose of the Study:

• To investigate the impact of mTOR inhibition on brain pericyte contraction and viability during ischemia.
• To evaluate the therapeutic potential of rapamycin in a mouse model of ischemic stroke.

Main Methods:

• In vitro study of cultured pericytes under simulated ischemia.
• Assessment of pericyte contraction and viability with and without rapamycin.
• In vivo study using a mouse model of middle cerebral artery occlusion and recanalization.

Main Results:

• Pericytes contracted within 1 hour and died after 7 hours of simulated ischemia.
• Rapamycin significantly reduced pericyte contraction rate but did not affect viability.
• Rapamycin increased capillary diameter and the number of open capillaries post-stroke in mice.

Conclusions:

• mTOR inhibition by rapamycin mitigates pericyte contraction during ischemia via a calcium-independent pathway.
• Rapamycin enhances cerebral reperfusion by improving capillary patency after stroke.
• Rapamycin shows promise as an adjuvant therapy to improve outcomes post-ischemic stroke.