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Titolo:
Adenovirus-mediated GDNF and CNTF pretreatment protects against striatal injury following transient middle cerebral artery occlusion in mice
Autore:
Hermann, DM; Kilic, E; Kugler, S; Isenmann, S; Bahr, M;
Indirizzi:
Univ Tubingen, Dept Neurol, D-72076 Tubingen, Germany Univ Tubingen Tubingen Germany D-72076 Neurol, D-72076 Tubingen, Germany
Titolo Testata:
NEUROBIOLOGY OF DISEASE
fascicolo: 4, volume: 8, anno: 2001,
pagine: 655 - 666
SICI:
0969-9961(200108)8:4<655:AGACPP>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
CILIARY NEUROTROPHIC FACTOR; RETINAL GANGLION-CELLS; CORTICAL SPREADING DEPRESSION; DELAYED NEURONAL DEATH; ISCHEMIC BRAIN INJURY; IN-VIVO; GENE-TRANSFER; RAT-BRAIN; DIFFERENTIAL REGULATION; TOPICAL APPLICATION;
Keywords:
focal cerebral ischemia; intraluminar thread occlusion; adenoviral gene therapy; adenoviral transfer; neurotrophic factor; neuroprotection;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Hermann, DM Univ Tubingen, Dept Neurol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany Univ Tubingen Hoppe Seyler Str 3 Tubingen Germany D-72076 any
Citazione:
D.M. Hermann et al., "Adenovirus-mediated GDNF and CNTF pretreatment protects against striatal injury following transient middle cerebral artery occlusion in mice", NEUROBIOL D, 8(4), 2001, pp. 655-666

Abstract

During the last few years, adenoviral gene transfer techniques have achieved increasing interest in the treatment of neurodegenerative diseases. However, gene therapy requires that delivered genes are translated into proteins. This may pose a problem in focal ischemia where protein synthesis is compromized. The present study was conducted to find out the feasibility of adenoviral GDNF and CNTF delivery in transient focal ischemia, as induced by 30 min of intraluminar middle cerebral artery (MCA) occlusion in mice. Injections of vehicle, of an adenoviral vector deleted in the El region (Ad-dE1) and of vectors expressing the GDNF (Ad-GDNF), CNTF (Ad-CNTF), or GFP (Ad-EGFP) gene from a CMV promoter were stereotactically placed in the dorsolateral striatum, i.e., the core of the MCA territory, and focal ischemia was induced seven days later. Thread occlusion resulted in disseminated injury of the striatum, but not the overlying cortex. The number of viable neuronswas significantly increased after I and 3 days of reperfusion both in Ad-GDNF and Ad-CNTF as compared with vehicle or Ad-dE1-treated animals, whereasthe number of injured cells was significantly reduced, as shown by cresyl violet staining, terminal transferase biotinylated-dUTP nick end-labeling (TUNEL), and immunocytochemistry for activated caspase-3. Interestingly, theprotective effects of Ad-GDNF were similarly strong in areas of the striatum adjacent and remote of the adenoviral infusion site, while Ad-CNTF showed pronounced rescue effects in the surrounding, but rather little effects distant to the infusion. The present study demonstrates that adenoviral delivery of neurotrophic factors may be a useful tool for the treatment of focal ischemia. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 01:21:41