Publicação
Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity
| 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 |
| _version_ | 1866877991239286784 |
|---|---|
| author | Zhao, X. |
| author2 | Jin, L. Zhu, Z. Lu, H. Shi, H. Zhong, Q. Oliveira, J. M. Reis, R. L. Gao, C. Zhengwei, M. |
| author2_role | author author author author author author author author author |
| author_facet | Zhao, X. Jin, L. Zhu, Z. Lu, H. Shi, H. Zhong, Q. Oliveira, J. M. Reis, R. L. Gao, C. Zhengwei, M. |
| author_role | author |
| contributor_name_str_mv | Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Zhao, X.\"},{\"Person.name\":\"Jin, L.\"},{\"Person.name\":\"Zhu, Z.\"},{\"Person.name\":\"Lu, H.\"},{\"Person.name\":\"Shi, H.\"},{\"Person.name\":\"Zhong, Q.\"},{\"Person.name\":\"Oliveira, J. M.\"},{\"Person.name\":\"Reis, R. L.\"},{\"Person.name\":\"Gao, C.\"},{\"Person.name\":\"Zhengwei, M.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Zhao, X. Jin, L. Zhu, Z. Lu, H. Shi, H. Zhong, Q. Oliveira, J. M. Reis, R. L. Gao, C. Zhengwei, M. |
| datacite.date.Accepted.fl_str_mv | 2021-06-01T00:00:00Z |
| datacite.date.embargoed.fl_str_mv | 10000-01-01T00:00:00Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.subjects.subject.fl_str_mv | Dextran Microgel Spinal cord injury Excitotoxicity GVIA Motor functional recovery |
| datacite.titles.title.fl_str_mv | Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity |
| dc.contributor.none.fl_str_mv | Universidade do Minho |
| dc.creator.none.fl_str_mv | Zhao, X. Jin, L. Zhu, Z. Lu, H. Shi, H. Zhong, Q. Oliveira, J. M. Reis, R. L. Gao, C. Zhengwei, M. |
| dc.date.Accepted.fl_str_mv | 2021-06-01T00:00:00Z |
| dc.date.embargoed.fl_str_mv | 10000-01-01T00:00:00Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/73988 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| dc.subject.none.fl_str_mv | Dextran Microgel Spinal cord injury Excitotoxicity GVIA Motor functional recovery |
| dc.title.fl_str_mv | Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | restrictedAccess |
| format | article |
| fulltext.url.fl_str_mv | https://prod-dspace.uminho.pt/bitstreams/952182fd-c9c0-4462-8454-d1da6dfd11c9/download |
| id | rum_feefa2fc06046ceca42e02c473c6a7e5 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/73988 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/73988 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Zhao, X. Jin, L. Zhu, Z. Lu, H. Shi, H. Zhong, Q. Oliveira, J. M. Reis, R. L. Gao, C. Zhengwei, M. |
| publishDate | 2021 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engElsevierporSpinal 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.application/pdfporConotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicityZhao, X.Jin, L.Zhu, Z.Lu, H.Shi, H.Zhong, Q.Oliveira, J. M.Reis, R. L.Gao, C.Zhengwei, M.HostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptISSNIsPartOf2352-9407DOIIsPartOf10.1016/j.apmt.2021.1010642021-062021-032021-09-10T08:16:05Z2021-06-01T00:00:00Z10000-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/73988http://purl.org/coar/access_right/c_16ecrestricted accessDextranMicrogelSpinal cord injuryExcitotoxicityGVIAMotor functional recovery3812655 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_f1cfapplication/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/952182fd-c9c0-4462-8454-d1da6dfd11c9/download |
| spellingShingle | Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity Zhao, X. Dextran Microgel Spinal cord injury Excitotoxicity GVIA Motor functional recovery |
| status | SINGLETON |
| subject.fl_str_mv | Dextran Microgel Spinal cord injury Excitotoxicity GVIA Motor functional recovery |
| title | Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity |
| title_full | Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity |
| title_fullStr | Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity |
| title_full_unstemmed | Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity |
| title_short | Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity |
| title_sort | Conotoxin loaded dextran microgel particles alleviate effects of spinal cord injury by inhibiting neuronal excitotoxicity |
| topic | Dextran Microgel Spinal cord injury Excitotoxicity GVIA Motor functional recovery |
| topic_facet | Dextran Microgel Spinal cord injury Excitotoxicity GVIA Motor functional recovery |
| url | https://hdl.handle.net/1822/73988 |
| visible | 1 |