Rapamycin up-regulation of autophagy reduces infarct size and improves outcomes in both permanent MCAL, and embolic MCAO, murine models of stroke.
Kathleen M BuckleyDaniel L HessIrina Y SazonovaSudharsan Periyasamy-ThandavanJohn R BarrettRussell KirksHarrison GraceGalina KondrikovaMaribeth H JohnsonDavid C HessPatricia V SchoenleinMd Nasrul HodaWilliam D HillPublished in: Experimental & translational stroke medicine (2014)
While both inhibition and enhancement of autophagy by pharmacological intervention decreased lesion size and improved neurological scores, the enhancement with rapamycin showed a greater degree of improvement in outcomes as well as in survival. The protective action seen with chloroquine may be in part due to off-target effects on apoptosis separate from blocking lysosomal activity in autophagy. We conclude pharmacologic induction of autophagy is more advantageous than its blockade in physiologically-relevant permanent and slow reperfusion stroke models.
Keyphrases
- endoplasmic reticulum stress
- cell death
- oxidative stress
- signaling pathway
- atrial fibrillation
- cerebral ischemia
- randomized controlled trial
- acute myocardial infarction
- metabolic syndrome
- type diabetes
- heart failure
- acute ischemic stroke
- adipose tissue
- brain injury
- percutaneous coronary intervention
- insulin resistance
- left ventricular
- acute coronary syndrome
- weight loss