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Article: Inhibition of caspases promotes long-term survival and reinnervation by axotomized spinal motoneurons of denervated muscle in newborn rats

TitleInhibition of caspases promotes long-term survival and reinnervation by axotomized spinal motoneurons of denervated muscle in newborn rats
Authors
Issue Date2003
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexnr
Citation
Experimental Neurology, 2003, v. 181 n. 2, p. 190-203 How to Cite?
AbstractWe examined whether (1) a pan-caspase inhibitor, Boc-D-FMK, exerts long-term neuroprotective effects on spinal motoneurons (MNs) after root avulsion in neonatal rats and (2) whether the rescued spinal MNs regenerate their axons into a peripheral nerve (PN) graft and reinnervate a previously denervated target muscle. Eight weeks after root avulsion, 67% of spinal MNs remained in the Boc-D-FMK-treated group, whereas all MNs died in the sham control group. By 12 weeks postinjury, however, all Boc-D-FMK treated MNs died. In the regeneration experiment, a PN graft was implanted at different times after injury. The animals were allowed to survive for 4 weeks following the operation. Without caspase inhibition, MNs did not regenerate at any time point. In animals treated with Ac-DEVD-CHO, a caspase-3-specific inhibitor, and Boc-D-FMK, 44 and 62% of MNs, respectively, were found to regenerate their axons into a PN graft implanted immediately after root avulsion. When the PN graft was implanted 2 weeks after injury, however, MNs failed to regenerate following Ac-DEVD-CHO treatment, whereas 53% of MNs regenerated their axons into the graft after treatment with Boc-D-FMK. No regeneration was observed when a PN graft was implanted later than 2 weeks after injury. In the reinnervation study, injured MNs and the target biceps muscle were reconnected by a PN bridge implanted 2 weeks after root avulsion with administration of Boc-D-FMK. Eight weeks following the operation, 39% of MNs reinnervated the biceps muscle. Morphologically normal synapses and motor endplates were reformed in the muscle fibers. Collectively, these data provide evidence that injured neonatal motoneurons can survive and reinnervate peripheral muscle targets following inhibition of caspases. © 2003 Elsevier Science (USA). All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/149616
ISSN
2015 Impact Factor: 4.657
2015 SCImago Journal Rankings: 2.427
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, YMen_US
dc.contributor.authorYick, LWen_US
dc.contributor.authorYip, HKen_US
dc.contributor.authorSo, KFen_US
dc.contributor.authorOppenheim, RWen_US
dc.contributor.authorWu, Wen_US
dc.date.accessioned2012-06-26T05:56:05Z-
dc.date.available2012-06-26T05:56:05Z-
dc.date.issued2003en_US
dc.identifier.citationExperimental Neurology, 2003, v. 181 n. 2, p. 190-203en_US
dc.identifier.issn0014-4886en_US
dc.identifier.urihttp://hdl.handle.net/10722/149616-
dc.description.abstractWe examined whether (1) a pan-caspase inhibitor, Boc-D-FMK, exerts long-term neuroprotective effects on spinal motoneurons (MNs) after root avulsion in neonatal rats and (2) whether the rescued spinal MNs regenerate their axons into a peripheral nerve (PN) graft and reinnervate a previously denervated target muscle. Eight weeks after root avulsion, 67% of spinal MNs remained in the Boc-D-FMK-treated group, whereas all MNs died in the sham control group. By 12 weeks postinjury, however, all Boc-D-FMK treated MNs died. In the regeneration experiment, a PN graft was implanted at different times after injury. The animals were allowed to survive for 4 weeks following the operation. Without caspase inhibition, MNs did not regenerate at any time point. In animals treated with Ac-DEVD-CHO, a caspase-3-specific inhibitor, and Boc-D-FMK, 44 and 62% of MNs, respectively, were found to regenerate their axons into a PN graft implanted immediately after root avulsion. When the PN graft was implanted 2 weeks after injury, however, MNs failed to regenerate following Ac-DEVD-CHO treatment, whereas 53% of MNs regenerated their axons into the graft after treatment with Boc-D-FMK. No regeneration was observed when a PN graft was implanted later than 2 weeks after injury. In the reinnervation study, injured MNs and the target biceps muscle were reconnected by a PN bridge implanted 2 weeks after root avulsion with administration of Boc-D-FMK. Eight weeks following the operation, 39% of MNs reinnervated the biceps muscle. Morphologically normal synapses and motor endplates were reformed in the muscle fibers. Collectively, these data provide evidence that injured neonatal motoneurons can survive and reinnervate peripheral muscle targets following inhibition of caspases. © 2003 Elsevier Science (USA). All rights reserved.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexnren_US
dc.relation.ispartofExperimental Neurologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnimals, Newbornen_US
dc.subject.meshAxotomyen_US
dc.subject.meshBenzyl Compounds - Pharmacologyen_US
dc.subject.meshCaspases - Antagonists & Inhibitorsen_US
dc.subject.meshCell Counten_US
dc.subject.meshCell Survival - Drug Effectsen_US
dc.subject.meshCysteine Proteinase Inhibitors - Pharmacologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshHydrocarbons, Fluorinated - Pharmacologyen_US
dc.subject.meshMotor Neurons - Drug Effects - Physiologyen_US
dc.subject.meshMuscle Denervationen_US
dc.subject.meshMuscle, Skeletal - Innervation - Pathologyen_US
dc.subject.meshNerve Regeneration - Drug Effects - Physiologyen_US
dc.subject.meshNeuroprotective Agents - Pharmacologyen_US
dc.subject.meshRadiculopathy - Pathology - Physiopathologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshTime Factorsen_US
dc.titleInhibition of caspases promotes long-term survival and reinnervation by axotomized spinal motoneurons of denervated muscle in newborn ratsen_US
dc.typeArticleen_US
dc.identifier.emailYip, HK:hkfyip@hku.hken_US
dc.identifier.emailSo, KF:hrmaskf@hkucc.hku.hken_US
dc.identifier.emailWu, W:wtwu@hkucc.hku.hken_US
dc.identifier.authorityYip, HK=rp00285en_US
dc.identifier.authoritySo, KF=rp00329en_US
dc.identifier.authorityWu, W=rp00419en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0014-4886(03)00023-2en_US
dc.identifier.pmid12781992-
dc.identifier.scopuseid_2-s2.0-0038392880en_US
dc.identifier.hkuros85076-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0038392880&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume181en_US
dc.identifier.issue2en_US
dc.identifier.spage190en_US
dc.identifier.epage203en_US
dc.identifier.isiWOS:000183391000007-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChan, YM=36989085800en_US
dc.identifier.scopusauthoridYick, LW=6603414804en_US
dc.identifier.scopusauthoridYip, HK=7101980864en_US
dc.identifier.scopusauthoridSo, KF=34668391300en_US
dc.identifier.scopusauthoridOppenheim, RW=7102628195en_US
dc.identifier.scopusauthoridWu, W=7407081122en_US

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