Neuroprotective effect of poly(lactic-co-glycolic acid) nanoparticle-bound brain-derived neurotrophic factor in a permanent middle cerebral artery occlusion model of ischemia in rats.

ABSTRACT

Poly (lactide­co­glycolide) (PLGA) nanoparticles (NPs) are biodegradable carriers that participate in the transport of neuroprotective drugs across the blood brain barrier (BBB). Targeted brain­derived neurotrophic factor (BDNF) delivery across the BBB could provide neuroprotection in brain injury. We tested the neuroprotective effect of PLGA nanoparticle­bound BDNF in a permanent middle cerebral artery occlusion (pMCAO) model of ischemia in rats. Sprague­Dawley rats were subjected to pMCAO. Four hours after pMCAO, two groups were intravenously treated with BDNF and NP­BDNF, respectively. Functional outcome was assessed at 2 and 24 h after pMCAO, using the modified neurologic severity score (mNSS) and rotarod performance tests. Following functional assessments, rats were euthanized blood was taken to assess levels of the neurobiomarkers neuron­specific enolase and S100 calcium­binding protein ß (S100ß), and the brain was evaluated to measure the infarct volume. The NP­BDNF­treated group showed significant improvement in mNSS compared with pMCAO and BDNF­treated groups and showed improved rotarod performance. The infarct volume in rats treated with NP­BDNFs was also significantly smaller. These results were further corroborated by correlating differences in estimated NSE and S100ß. NP­BDNFs exhibit a significant neuroprotective effect in the pMCAO model of ischemia in rats.