Matches in SemOpenAlex for { <https://semopenalex.org/work/W2579977726> ?p ?o ?g. }
Showing items 1 to 91 of
91
with 100 items per page.
- W2579977726 endingPage "E524" @default.
- W2579977726 startingPage "E523" @default.
- W2579977726 abstract "Short- and long-term effects of radiation on the central nervous system (CNS) cause axonal damage and neuronal death. The Clostridial exotoxin, C3 transferase (C3), inhibits RhoA to promote neuron survival and axon regrowth. C3 modified for increased permeability has been shown to restore some function in animal studies and a clinical trial of spinal cord trauma, but the lack of sustained C3 delivery has hampered clinically important physiologic improvement. We sought to develop an adeno-associated viral (AAV) vector to deliver C3, to improve axon regrowth and neuron survival. Using optic nerve crush (ONC) model of CNS injury in rodents, rats were intravitreally injected with AAV expressing full length, endogenous C3 (E-C3) or modified secretable, permeable C3 (SP-C3). After 1 week, ONC was performed. Twenty-seven days later, the anterograde axon tracer, cholera toxin B (CTB), was intravitreally injected. On the 28th day, the animal was sacrificed. The retina was stained for RGC-specific Brn3a to assess retinal ganglion cell (RGC) survival. In vitro, HEK 293T cells were transfected with plasmids expressing GFP-tagged truncated SP-C3 (SP-tC3), and Live-Dead Assay was used to assess toxicity. E-C3 and SP-C3 yielded significantly longer axons compared to their controls and saline. Compared to its control, E-C3 yielded 7.4-fold and 8.9-fold more axons at 100 um and 250 um post-crush. SP-C3 yielded the 2 longest axons, growing 1864 um and 1628 um post-crush. E-C3 yielded the third longest axon, at 1386 um. E-C3 increased RGC survival nearly 2-fold relative to its control. In vitro, SP-C3 significantly reduced survival at 24 and 72 hours relative to untreated controls, whereas SP-tC3 caused no significant survival difference. AAV-mediated delivery of C3 effectively promotes neuron survival and axon regrowth following ONC in vivo. While SP-C3 regenerates the longest axons, E-C3 regenerates more axons at 100 um and 250 um post-crush. E-C3 is neuroprotective in vivo. Finally, truncated SP-tC3 causes less cell death than full-length SP-C3 in vitro. Taken together, AAV efficiently delivers C3, increasing axon regrowth and neuron survival following CNS injury. Future lentiviral vectors in development may further improve control of delivery, and brain, spinal cord, and optic nerve radiation injury studies will facilitate assessment of physiologic improvement." @default.
- W2579977726 created "2017-02-03" @default.
- W2579977726 creator A5015264327 @default.
- W2579977726 creator A5015890102 @default.
- W2579977726 creator A5016594403 @default.
- W2579977726 creator A5018012332 @default.
- W2579977726 creator A5018621217 @default.
- W2579977726 creator A5019451025 @default.
- W2579977726 creator A5023758837 @default.
- W2579977726 creator A5036399957 @default.
- W2579977726 creator A5049441810 @default.
- W2579977726 creator A5065983314 @default.
- W2579977726 date "2015-11-01" @default.
- W2579977726 modified "2023-09-30" @default.
- W2579977726 title "Gene Therapy for Neuroprotection and Axon Regeneration Using a RhoA-Inhibitory C3 Transferase Transgene Adeno-Associated Viral Vector in a Rodent Optic Nerve Crush Model" @default.
- W2579977726 doi "https://doi.org/10.1016/j.ijrobp.2015.07.1886" @default.
- W2579977726 hasPublicationYear "2015" @default.
- W2579977726 type Work @default.
- W2579977726 sameAs 2579977726 @default.
- W2579977726 citedByCount "0" @default.
- W2579977726 crossrefType "journal-article" @default.
- W2579977726 hasAuthorship W2579977726A5015264327 @default.
- W2579977726 hasAuthorship W2579977726A5015890102 @default.
- W2579977726 hasAuthorship W2579977726A5016594403 @default.
- W2579977726 hasAuthorship W2579977726A5018012332 @default.
- W2579977726 hasAuthorship W2579977726A5018621217 @default.
- W2579977726 hasAuthorship W2579977726A5019451025 @default.
- W2579977726 hasAuthorship W2579977726A5023758837 @default.
- W2579977726 hasAuthorship W2579977726A5036399957 @default.
- W2579977726 hasAuthorship W2579977726A5049441810 @default.
- W2579977726 hasAuthorship W2579977726A5065983314 @default.
- W2579977726 hasBestOaLocation W25799777261 @default.
- W2579977726 hasConcept C104317684 @default.
- W2579977726 hasConcept C105702510 @default.
- W2579977726 hasConcept C111599444 @default.
- W2579977726 hasConcept C135983454 @default.
- W2579977726 hasConcept C153911025 @default.
- W2579977726 hasConcept C169760540 @default.
- W2579977726 hasConcept C25498285 @default.
- W2579977726 hasConcept C2777093970 @default.
- W2579977726 hasConcept C2777624874 @default.
- W2579977726 hasConcept C2778107364 @default.
- W2579977726 hasConcept C2779530196 @default.
- W2579977726 hasConcept C2780837183 @default.
- W2579977726 hasConcept C40767141 @default.
- W2579977726 hasConcept C529278444 @default.
- W2579977726 hasConcept C55493867 @default.
- W2579977726 hasConcept C71924100 @default.
- W2579977726 hasConcept C86803240 @default.
- W2579977726 hasConcept C92087593 @default.
- W2579977726 hasConcept C95444343 @default.
- W2579977726 hasConceptScore W2579977726C104317684 @default.
- W2579977726 hasConceptScore W2579977726C105702510 @default.
- W2579977726 hasConceptScore W2579977726C111599444 @default.
- W2579977726 hasConceptScore W2579977726C135983454 @default.
- W2579977726 hasConceptScore W2579977726C153911025 @default.
- W2579977726 hasConceptScore W2579977726C169760540 @default.
- W2579977726 hasConceptScore W2579977726C25498285 @default.
- W2579977726 hasConceptScore W2579977726C2777093970 @default.
- W2579977726 hasConceptScore W2579977726C2777624874 @default.
- W2579977726 hasConceptScore W2579977726C2778107364 @default.
- W2579977726 hasConceptScore W2579977726C2779530196 @default.
- W2579977726 hasConceptScore W2579977726C2780837183 @default.
- W2579977726 hasConceptScore W2579977726C40767141 @default.
- W2579977726 hasConceptScore W2579977726C529278444 @default.
- W2579977726 hasConceptScore W2579977726C55493867 @default.
- W2579977726 hasConceptScore W2579977726C71924100 @default.
- W2579977726 hasConceptScore W2579977726C86803240 @default.
- W2579977726 hasConceptScore W2579977726C92087593 @default.
- W2579977726 hasConceptScore W2579977726C95444343 @default.
- W2579977726 hasIssue "3" @default.
- W2579977726 hasLocation W25799777261 @default.
- W2579977726 hasOpenAccess W2579977726 @default.
- W2579977726 hasPrimaryLocation W25799777261 @default.
- W2579977726 hasRelatedWork W1970508859 @default.
- W2579977726 hasRelatedWork W2005377459 @default.
- W2579977726 hasRelatedWork W2024179689 @default.
- W2579977726 hasRelatedWork W2049862190 @default.
- W2579977726 hasRelatedWork W2075974900 @default.
- W2579977726 hasRelatedWork W2126892565 @default.
- W2579977726 hasRelatedWork W2137813821 @default.
- W2579977726 hasRelatedWork W2918408355 @default.
- W2579977726 hasRelatedWork W3135099246 @default.
- W2579977726 hasRelatedWork W3209827839 @default.
- W2579977726 hasVolume "93" @default.
- W2579977726 isParatext "false" @default.
- W2579977726 isRetracted "false" @default.
- W2579977726 magId "2579977726" @default.
- W2579977726 workType "article" @default.