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 (lactide-co-glycolide) (PLGA) nanoparticles (NPs) are biodegradable carriers that participate in the transport of neuroprotective drugs across the blood brain barrier (BBB). Targeted brain-derived neurotrophic factor (BDNF) delivery across the BBB could provide neuroprotection in brain injury. We tested the neuroprotective effect of PLGA nanoparticle-bound BDNF in a permanent middle cerebral artery occlusion (pMCAO) model of ischemia in rats. Sprague-Dawley rats were subjected to pMCAO. Four hours after pMCAO, two groups were intravenously treated with BDNF and NP-BDNF, 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 neuron-specific enolase and S100 calcium-binding protein β (S100β), and the brain was evaluated to measure the infarct volume. The NP-BDNF-treated group showed significant improvement in mNSS compared with pMCAO and BDNF-treated groups and showed improved rotarod performance. The infarct volume in rats treated with NP-BDNFs was also significantly smaller. These results were further corroborated by correlating differences in estimated NSE and S100β. NP-BDNFs exhibit a significant neuroprotective effect in the pMCAO model of ischemia in rats.

The Recent Applications of PLGA-Based Nanostructures for Ischemic Stroke

“…The modified neurologic severity score (mNSS) remained significantly higher in the post-BDNF-treated group by 14-fold ( p < 0.001), and it was improved in the post-NP-BDNF-treated group by a 7-fold decrease ( p < 0.001), when compared with sham-operated rats. Therefore, therapy with NP-BDNF decreased the infarct size, the severity of limb paralysis, and the expression of brain-tissue damage markers compared to BDNF administration [ 81 ]. Jaclyn et al created a BDNF delivery system using a hydrogel containing hyaluronic acid, methylcellulose (HAMC), and PLGA NPs and applied it directly to the epidermis directly above the stroke.…”