Preserving and enhancing mitochondrial function after stroke to protect and repair the neurovascular unit: novel opportunities for nanoparticle-based drug delivery

The neurovascular unit (NVU) is composed of vascular cells, glia, and neurons that form the basic component blood brain barrier. This intricate structure rapidly adjusts cerebral flow to match metabolic needs activity. However, NVU exquisitely sensitive damage displays limited repair after a stroke. To effectively treat stroke, it therefore considered crucial both protect NVU. Mitochondrial calcium (Ca 2+ ) uptake supports function by buffering Ca stimulating energy production. excessive mitochondrial causes toxic overloading triggers numerous cell death pathways which destroy one earliest pathological events in Drugs preserve integrity should confer profound protection blocking initiation injury events. We have shown efflux are mediated uniporter complex (MCU cx sodium/Ca /lithium exchanger (NCLX), respectively. Moreover, our recent pharmacological studies demonstrated MCU inhibition NCLX activation suppress ischemic excitotoxic neuronal overloading. These findings suggest combining with markedly In terms promoting repair, nuclear hormone receptor promising approach. Retinoid X (RXR) thyroid (TR) agonists activate complementary transcriptional programs stimulate biogenesis, inflammation, enhance production new neurons. RXR TR agonism thus further improve clinical benefits increasing repair. drugs either inhibit , or NCLX, TR, suffer from adverse effects caused undesired actions on healthy tissues. overcome this problem, we describe use nanoparticle drug formulations preferentially target metabolically compromised damaged NVUs an hemorrhagic nanoparticle-based approaches potential safety efficacy maximizing delivery diseased minimizing exposure peripheral