File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Treatment of traumatic brain injury using zinc-finger protein gene therapy targeting VEGF-A

TitleTreatment of traumatic brain injury using zinc-finger protein gene therapy targeting VEGF-A
Authors
Keywordselectrophysiology
Adeno-associated virus
adenovirus
gene therapy
microvasculature
traumatic brain injury
Issue Date2012
Citation
Journal of Neurotrauma, 2012, v. 29, n. 17, p. 2647-2659 How to Cite?
AbstractVascular endothelial growth factor (VEGF) plays a role in angiogenesis and has been shown to be neuroprotective following central nervous system trauma. In the present study we evaluated the pro-angiogenic and neuroprotective effects of an engineered zinc-finger protein transcription factor transactivator targeting the vascular endothelial growth factor A (VEGF-ZFP). We used two virus delivery systems, adeno-virus and adeno-associated virus, to examine the effects of early and delayed VEGF-A upregulation after brain trauma, respectively. Male Sprague-Dawley rats were subject to a unilateral fluid percussion injury (FPI) of moderate severity (2.2-2.5atm) followed by intracerebral microinjection of either adenovirus vector (Adv) or an adeno-associated vector (AAV) carrying the VEGF-ZFP construct. Adv-VEGF-ZFP-treated animals had significantly fewer TUNEL positive cells in the injured penumbra of the cortex (p<0.001) and hippocampus (p=0.001) relative to untreated rats at 72h post-injury. Adv-VEGF-ZFP treatment significantly improved fEPSP values (p=0.007) in the CA1 region relative to injury alone. Treatment with AAV2-VEGF-ZFP resulted in improved post-injury microvascular diameter and improved functional recovery on the balance beam and rotarod task at 30 days post-injury. Collectively, the results provide supportive evidence for the concept of acute and delayed treatment following TBI using VEGF-ZFP to induce angiogenesis, reduce cell death, and enhance functional recovery. © Mary Ann Liebert, Inc..
Persistent Identifierhttp://hdl.handle.net/10722/205780
ISSN
2015 Impact Factor: 4.377
2015 SCImago Journal Rankings: 1.945
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSiddiq, Ishita P.-
dc.contributor.authorPark, Eugene-
dc.contributor.authorLiu, Elaine-
dc.contributor.authorSpratt, Sharon Kaye-
dc.contributor.authorSurosky, Richard T.-
dc.contributor.authorLee, Gary-
dc.contributor.authorAndo, Dale-
dc.contributor.authorGiedlin, Martin A.-
dc.contributor.authorHaré, Gregory M T-
dc.contributor.authorFehlings, Michael George-
dc.contributor.authorBaker, Andrew J.-
dc.date.accessioned2014-10-06T08:02:20Z-
dc.date.available2014-10-06T08:02:20Z-
dc.date.issued2012-
dc.identifier.citationJournal of Neurotrauma, 2012, v. 29, n. 17, p. 2647-2659-
dc.identifier.issn0897-7151-
dc.identifier.urihttp://hdl.handle.net/10722/205780-
dc.description.abstractVascular endothelial growth factor (VEGF) plays a role in angiogenesis and has been shown to be neuroprotective following central nervous system trauma. In the present study we evaluated the pro-angiogenic and neuroprotective effects of an engineered zinc-finger protein transcription factor transactivator targeting the vascular endothelial growth factor A (VEGF-ZFP). We used two virus delivery systems, adeno-virus and adeno-associated virus, to examine the effects of early and delayed VEGF-A upregulation after brain trauma, respectively. Male Sprague-Dawley rats were subject to a unilateral fluid percussion injury (FPI) of moderate severity (2.2-2.5atm) followed by intracerebral microinjection of either adenovirus vector (Adv) or an adeno-associated vector (AAV) carrying the VEGF-ZFP construct. Adv-VEGF-ZFP-treated animals had significantly fewer TUNEL positive cells in the injured penumbra of the cortex (p<0.001) and hippocampus (p=0.001) relative to untreated rats at 72h post-injury. Adv-VEGF-ZFP treatment significantly improved fEPSP values (p=0.007) in the CA1 region relative to injury alone. Treatment with AAV2-VEGF-ZFP resulted in improved post-injury microvascular diameter and improved functional recovery on the balance beam and rotarod task at 30 days post-injury. Collectively, the results provide supportive evidence for the concept of acute and delayed treatment following TBI using VEGF-ZFP to induce angiogenesis, reduce cell death, and enhance functional recovery. © Mary Ann Liebert, Inc..-
dc.languageeng-
dc.relation.ispartofJournal of Neurotrauma-
dc.subjectelectrophysiology-
dc.subjectAdeno-associated virus-
dc.subjectadenovirus-
dc.subjectgene therapy-
dc.subjectmicrovasculature-
dc.subjecttraumatic brain injury-
dc.titleTreatment of traumatic brain injury using zinc-finger protein gene therapy targeting VEGF-A-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1089/neu.2012.2444-
dc.identifier.pmid23016562-
dc.identifier.scopuseid_2-s2.0-84870512593-
dc.identifier.volume29-
dc.identifier.issue17-
dc.identifier.spage2647-
dc.identifier.epage2659-
dc.identifier.eissn1557-9042-
dc.identifier.isiWOS:000311856400006-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats