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Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity

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Resumo:Spinal cord injury (SCI) is a severe refractory disabling condition accompanied by complicated patholog- ical 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 excita- tory 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 in- hibiting 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 neuropro- tective 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 con- tinuity 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.
Autores principais:Zhao, X.
Outros Autores:Jin, L.; Zhu, Z.; Lu, H.; Shi, H.; Zhong, Q.; Oliveira, J. M.; Reis, R. L.; Gao, C.; Zhengwei, M.
Assunto:Dextran Microgel Spinal cord injury Excitotoxicity GVIA Motor functional recovery
Ano:2021
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho

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