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

Siti Norsyafika Kamarudin,Minaketan Tripathy,Nafeeza Mohd Ismail,Renad Alyautdin,Igor Iezhitsa

doi:10.21307/ane-2020-001

Siti Norsyafika Kamarudin, Minaketan Tripathy + Show 3 more

Open Access

https://doi.org/10.21307/ane-2020-001

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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.

Highlights

Stroke remains a major health burden as the sec‐ ond leading cause of death worldwide, according to data published in 2012 by the World Health Organiza‐ tion
brain‐derived neurotrophic factor (BDNF) was incorporated into PLGA NPs, and subse‐ quent coating with poloxamer 188 (PLX188) was confirmed by particle size and zeta potential measurement
Incorporation of BDNF increased the average size of the naked PLGA NPs from 27.8 ± 5.28 nm to 106.7 ± 3.42 nm, and the subsequent coating of NPs with PLX188 further increased the size to 186.6 ± 19.11 nm (Table I)

Summary

Introduction

Stroke remains a major health burden as the sec‐ ond leading cause of death worldwide, according to data published in 2012 by the World Health Organiza‐ tion. Stroke can be defined as an umbrella of conditions caused by the occlusion or haemorrhage of cerebral blood vessels supplying the brain (Lo et al, 2003). In both cases, stroke involves the death and dysfunction of neuronal cells and neurologi‐ cal deficits that reflect the location and size of the com‐ promised brain area (Lo et al, 2003). Current ther‐ apies for AIS are inadequate, and the only approved medical therapy for AIS is tissue plasminogen activator (tPA), a thrombolytic agent that targets the thrombus within the blood vessel

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