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Article: Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury

TitleLithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury
Authors
KeywordsAxonal regeneration
Behavioral analysis
Chondroitin sulfate
Lithium
Rubrospinal tract
Spinal cord injury
Issue Date2004
PublisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/neu
Citation
Journal Of Neurotrauma, 2004, v. 21 n. 7, p. 932-943 How to Cite?
AbstractAfter spinal cord injury, enzymatic digestion of chondroitin sulfate proteoglycans promotes axonal regeneration of central nervous system neurons across the lesion scar. We examined whether chondroitinase ABC (ChABC) promotes the axonal regeneration of rubrospinal tract (RST) neurons following injury to the spinal cord. The effect of a GSK-3β inhibitor, lithium chloride (LiCl), on the regeneration of axotomized RST neurons was also assessed. Adult rats received a unilateral hemisection at the seventh cervical spinal cord segment (C7). Four weeks after different treatments, regeneration of RST axons across the lesion scar was examined by injection of Fluoro-Gold at spinal segment T2, and locomotor recovery was studied by a test of forelimb usage. Injured RST axons did not regenerate spontaneously after spinal cord injury, and intraperitoneal injection of LiCl alone did not promote the regeneration of RST axons. Administration of ChABC at the lesion site enhanced the regeneration of RST axons by 20%. Combined treatment of LiCl together with ChABC significantly increased the regeneration of RST axons to 42%. Animals receiving combined treatment used both forelimbs together more often than animals that received sham or single treatment. Immunoblotting and immunohistochemical analysis revealed that LiCl induced the expression of inactive GSK-3β as well as the upregulation of Bcl-2 in injured RST neurons. These results indicate that in vivo, LiCl inhibits GSK-3β and reinforces the regeneration-promoting function of ChABC through a Bcl-2-dependent mechanism. Combined use of LiCl together with ChABC could be a novel treatment for spinal cord injury.
Persistent Identifierhttp://hdl.handle.net/10722/67665
ISSN
2015 Impact Factor: 4.377
2015 SCImago Journal Rankings: 1.945
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYick, LWen_HK
dc.contributor.authorSo, KFen_HK
dc.contributor.authorCheung, PTen_HK
dc.contributor.authorWu, WTen_HK
dc.date.accessioned2010-09-06T05:57:10Z-
dc.date.available2010-09-06T05:57:10Z-
dc.date.issued2004en_HK
dc.identifier.citationJournal Of Neurotrauma, 2004, v. 21 n. 7, p. 932-943en_HK
dc.identifier.issn0897-7151en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67665-
dc.description.abstractAfter spinal cord injury, enzymatic digestion of chondroitin sulfate proteoglycans promotes axonal regeneration of central nervous system neurons across the lesion scar. We examined whether chondroitinase ABC (ChABC) promotes the axonal regeneration of rubrospinal tract (RST) neurons following injury to the spinal cord. The effect of a GSK-3β inhibitor, lithium chloride (LiCl), on the regeneration of axotomized RST neurons was also assessed. Adult rats received a unilateral hemisection at the seventh cervical spinal cord segment (C7). Four weeks after different treatments, regeneration of RST axons across the lesion scar was examined by injection of Fluoro-Gold at spinal segment T2, and locomotor recovery was studied by a test of forelimb usage. Injured RST axons did not regenerate spontaneously after spinal cord injury, and intraperitoneal injection of LiCl alone did not promote the regeneration of RST axons. Administration of ChABC at the lesion site enhanced the regeneration of RST axons by 20%. Combined treatment of LiCl together with ChABC significantly increased the regeneration of RST axons to 42%. Animals receiving combined treatment used both forelimbs together more often than animals that received sham or single treatment. Immunoblotting and immunohistochemical analysis revealed that LiCl induced the expression of inactive GSK-3β as well as the upregulation of Bcl-2 in injured RST neurons. These results indicate that in vivo, LiCl inhibits GSK-3β and reinforces the regeneration-promoting function of ChABC through a Bcl-2-dependent mechanism. Combined use of LiCl together with ChABC could be a novel treatment for spinal cord injury.en_HK
dc.languageengen_HK
dc.publisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/neuen_HK
dc.relation.ispartofJournal of Neurotraumaen_HK
dc.rightsThis is a copy of an article published in the [Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury] © [2004] [copyright Mary Ann Liebert, Inc.]; [Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury} is available online at: http://www.liebertonline.com.</-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAxonal regenerationen_HK
dc.subjectBehavioral analysisen_HK
dc.subjectChondroitin sulfateen_HK
dc.subjectLithiumen_HK
dc.subjectRubrospinal tracten_HK
dc.subjectSpinal cord injuryen_HK
dc.subject.meshAdjuvants, Immunologic - therapeutic useen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCervical Vertebraeen_HK
dc.subject.meshChondroitin ABC Lyase - metabolism - pharmacologyen_HK
dc.subject.meshDrug Synergismen_HK
dc.subject.meshImage Processing, Computer-Assisteden_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshLithium Chloride - therapeutic useen_HK
dc.subject.meshMotor Activity - drug effectsen_HK
dc.subject.meshNerve Regeneration - drug effectsen_HK
dc.subject.meshNeurons - drug effects - pathologyen_HK
dc.subject.meshProto-Oncogene Proteins c-bcl-2 - biosynthesis - drug effectsen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Sprague-Dawleyen_HK
dc.subject.meshRecovery of Functionen_HK
dc.subject.meshSpinal Cord Injuries - drug therapy - pathologyen_HK
dc.titleLithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injuryen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0897-7151&volume=21 no 7&spage=932&epage=943&date=2004&atitle=Lithium+chloride+reinforces+the+regeneration-promoting+effect+of+chondroitinase+ABC+on+rubrospinal+neurons+after+spinal+cord+injuryen_HK
dc.identifier.emailSo, KF:hrmaskf@hkucc.hku.hken_HK
dc.identifier.emailCheung, PT:ptcheung@hkucc.hku.hken_HK
dc.identifier.emailWu, WT:wtwu@hkucc.hku.hken_HK
dc.identifier.authoritySo, KF=rp00329en_HK
dc.identifier.authorityCheung, PT=rp00351en_HK
dc.identifier.authorityWu, WT=rp00419en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1089/0897715041526221en_HK
dc.identifier.pmid15307905en_HK
dc.identifier.scopuseid_2-s2.0-3242879990en_HK
dc.identifier.hkuros95599en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-3242879990&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume21en_HK
dc.identifier.issue7en_HK
dc.identifier.spage932en_HK
dc.identifier.epage943en_HK
dc.identifier.isiWOS:000222973800010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYick, LW=6603414804en_HK
dc.identifier.scopusauthoridSo, KF=34668391300en_HK
dc.identifier.scopusauthoridCheung, PT=7202595465en_HK
dc.identifier.scopusauthoridWu, WT=7407081122en_HK

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