Neuroprotective ferulic acid (FA)–glycol chitosan (GC) nanoparticles for functional restoration of traumatically injured spinal cord

Abstract

An urgent unmet need exists for early-stage treatment of spinal cord injury (SCI). Currently methylprednisolone is the only therapeutic agent used in clinics, for which the efficacy is controversial and the side effect is well-known. We demonstrated functional restoration of injured spinal cord by self-assembled nanoparticles composed of ferulic acid modified glycol chitosan (FA-GC). Chitosan and ferulic acid are strong neuroprotective agents but their systemic delivery is difficult. Our data has shown a prolonged circulation time of the FA-GC nanoparticles allowing for effective delivery of both chitosan and ferulic acid to the injured site. Furthermore, the nanoparticles were found both in the gray matter and white matter. The in vitro tests demonstrated that nanoparticles protected primary neurons from glutamate-induced excitotoxicity. Using a spinal cord contusion injury model, significant recovery in locomotor function was observed in rats that were intravenously administered nanoparticles at 2 h post injury, as compared to non-improvement by methylprednisolone administration. Histological analysis revealed that FA-GC treatment significantly preserved axons and myelin and also reduced cavity volume, astrogliosis, and inflammatory response at the lesion site. No obvious adverse effects of nanoparticles to other organs were found. The restorative effect of FA-GC presents a promising potential for treating human SCIs.

Comparative study of neuropharmacological, analgesic properties and phenolic profile of Ajwah, Safawy and Sukkari cultivars of date palm (Phoenix dactylifera)

“…Neuroprotective effect of these two flavonols is well established and the mechanism of action is believed to be their antioxidant activity and beneficial actions on brain cells which include positive effects on mood (Mandel and Youdim 2004; Nehlig 2013). Although neuroprotection by hydroxycinnamic acids can be much less as compared to catechins, the effect of trans -ferulic acid cannot be ruled out since it is reported to exert neuroprotective effect in in-vivo and in-vitro tests and its antioxidant capacity might be the contributing factor for such activity (Cheng et al 2008; Luo and Sun 2011; Wu et al 2014). The traditional use of date plam in headache prompted us to test the extracts for antinociceptive activity.…”

Strategies to improve nerve regeneration after radical prostatectomy: a narrative review

“…(i) Neuroprotective/neuroregenerative effect [84] (ii) Antitumoral activity [95] (iii) Antinflammatory and analgesic effect [96] (iv) Hemostatic activity [97] (v) Antimicrobial activity [98] In vitro studies on chitosan membrane showed its suitability as a substrate for proliferation, survival of Schwann cells as well as survival and differentiation of neuronal cells.…”

Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury

“…PLGA-NPs and carboxymethylchitosan/polyamidoamine dendrimers loaded with MP have shown significant reduction in the lesion size, improved behavioral outcomes, suppression of microglial and astrocytic responses and improved axon regeneration in hemisection SCI models (84, 85). Systemic administration of ferulic acid (FA)- glycol chitosan (GC) (FA-GC) NPs was reported to cause improvements in locomotion, axonal and myelin protection, attributed to the neuroprotective properties of FA and GC which extend anti-oxidative effects to prevent inflammation and excitotoxicity (86). Administration of small molecule inhibitors such as Chicago sky blue, a macrophage migration inhibitory factor, encapsulated in NPs increased white matter and blood vessel integrity post-SCI (87), but demonstrated activation of both pro- and anti-inflammatory signals which could be ascribed to dynamic changes in macrophage phenotypes while still being reparative in nature (88).…”