Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity. (June 2021)

• Record Type: Journal Article
• Authors: Zhao, Xinlian; Jin, Lulu; Zhu, Zhixin; Lu, Haohao; Shi, Haifei; Zhong, Qi; Oliveira, Joaquim Miguel; Reis, Rui L.; Gao, Changyou; Mao, Zhengwei
• Is Part Of: Applied materials today. Volume 23(2021)
• Publication Date: 2021-06
• Subjects: Excitotoxicity -- Spinal cord injury -- Microgel -- GVIA -- Motor functional recovery; Materials science -- Periodicals; Materials -- Research -- Periodicals; 620.1105
• DOI: 10.1016/j.apmt.2021.101064
• Languages: English
• ISSNs: 2352-9407

Abstract

Highlights: GVIA-loaded microgels were prepared to alleviate excitotoxicity after SCI. DexGVIA can adsorb glutamate/Ca 2+ to attenuate neuron-toxic microenvironment. DexGVIA reduce intracellular Ca 2+ concentration via sustained release of GVIA. DexGVIA increase the integrity and continuity of spinal cord structure after SCI. DexGVIA promote neurons/gliacytes regeneration, and improve motor function recovery. Abstract: Spinal cord injury (SCI) is a severe refractory disabling condition accompanied by complicated pathological processes, such as excessive glutamate release in the extracellular environment and massive influx of Ca 2+ into cells. Dextran can absorb extracellular glutamate and Ca 2+ to attenuate persistent excitatory processes that are detrimental to normal cells. Calcium channel inhibitors reduce the influx of Ca 2+, thereby relieving subsequent cytotoxicity such as mitochondria damage. Here, a bifunctional microgel was designed for delivering GVIA, an N-type calcium ion channel blocker, to achieve a combinational therapy of simultaneously reducing the Ca 2+ and glutamate concentrations in extracellular environment and inhibiting excess Ca 2+ influx. The obtained dextran microgels could effectively encapsulate GVIA peptide, which displayed sustained release. Microgels loaded with GVIA (DexGVIA) played an excellent neuroprotective role by relieving the influx of Ca 2+ in vitro . DexGVIA also exhibited promising therapeutic effect in vivo via reducing the lesion cavity, saving neurons and gliacytes from the injury, and improving continuity and integrity of the spinal cord, thus distinctly accelerated motor functional recovery of SCI rats. Our work provided a combinational strategy against excitotoxicity, with potential applications not only in SCI, but also in other pathologically similar conditions of the central nervous system. Graphical abstract: Image, graphical abstract