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- Publisher Website: 10.1089/neu.2012.2444
- Scopus: eid_2-s2.0-84870512593
- PMID: 23016562
- WOS: WOS:000311856400006
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Article: Treatment of traumatic brain injury using zinc-finger protein gene therapy targeting VEGF-A
Title | Treatment of traumatic brain injury using zinc-finger protein gene therapy targeting VEGF-A |
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Authors | |
Keywords | electrophysiology Adeno-associated virus adenovirus gene therapy microvasculature traumatic brain injury |
Issue Date | 2012 |
Citation | Journal of Neurotrauma, 2012, v. 29, n. 17, p. 2647-2659 How to Cite? |
Abstract | Vascular 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 Identifier | http://hdl.handle.net/10722/205780 |
ISSN | 2023 Impact Factor: 3.9 2023 SCImago Journal Rankings: 1.483 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Siddiq, Ishita P. | - |
dc.contributor.author | Park, Eugene | - |
dc.contributor.author | Liu, Elaine | - |
dc.contributor.author | Spratt, Sharon Kaye | - |
dc.contributor.author | Surosky, Richard T. | - |
dc.contributor.author | Lee, Gary | - |
dc.contributor.author | Ando, Dale | - |
dc.contributor.author | Giedlin, Martin A. | - |
dc.contributor.author | Haré, Gregory M T | - |
dc.contributor.author | Fehlings, Michael George | - |
dc.contributor.author | Baker, Andrew J. | - |
dc.date.accessioned | 2014-10-06T08:02:20Z | - |
dc.date.available | 2014-10-06T08:02:20Z | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | Journal of Neurotrauma, 2012, v. 29, n. 17, p. 2647-2659 | - |
dc.identifier.issn | 0897-7151 | - |
dc.identifier.uri | http://hdl.handle.net/10722/205780 | - |
dc.description.abstract | Vascular 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.language | eng | - |
dc.relation.ispartof | Journal of Neurotrauma | - |
dc.subject | electrophysiology | - |
dc.subject | Adeno-associated virus | - |
dc.subject | adenovirus | - |
dc.subject | gene therapy | - |
dc.subject | microvasculature | - |
dc.subject | traumatic brain injury | - |
dc.title | Treatment of traumatic brain injury using zinc-finger protein gene therapy targeting VEGF-A | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1089/neu.2012.2444 | - |
dc.identifier.pmid | 23016562 | - |
dc.identifier.scopus | eid_2-s2.0-84870512593 | - |
dc.identifier.volume | 29 | - |
dc.identifier.issue | 17 | - |
dc.identifier.spage | 2647 | - |
dc.identifier.epage | 2659 | - |
dc.identifier.eissn | 1557-9042 | - |
dc.identifier.isi | WOS:000311856400006 | - |
dc.identifier.issnl | 0897-7151 | - |