ArticleGene therapy2002
Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model.
Article in Gene therapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Intrathecal drug delivery in the era of nanomedicine.Advanced drug delivery reviews · 2020Pooled it
- Novel approaches for the delivery of therapeutics in ischemic stroke.Drug discovery today · 2020Review
- Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide.Biomedical reports · 2018Article
- Organ-targeted high-throughput in vivo biologics screen identifies materials for RNA delivery.Integrative biology : quantitative biosciences from nano to macro · 2014Article
- Temporal regulation of apoptotic and anti-apoptotic molecules after middle cerebral artery occlusion followed by reperfusion.Molecular neurobiology · 2014Review
- Mechanism underlying the protective effect of Kaixin Jieyu Fang on vascular depression following cerebral white matter damage.Neural regeneration research · 2014Article
- Bcl-2 enhances the formation of newborn striatal long-projection neurons in adult rat brain after a transient ischemic stroke.Neuroscience bulletin · 2012Article
- Purine nucleosides: endogenous neuroprotectants in hypoxic brain.Journal of neurochemistry · 2012Review
- Article
- In vitro and in vivo gene therapy with CMV vector-mediated presumed dog beta-nerve growth factor in pyridoxine-induced neuropathy dogs.Journal of veterinary science · 2008Article
- Nonviral gene transfection nanoparticles: function and applications in the brain.Nanomedicine : nanotechnology, biology, and medicine · 2008Review
- Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective opportunities.Molecular neurobiology · 2008Review
- Increased expression of a proline-rich Akt substrate (PRAS40) in human copper/zinc-superoxide dismutase transgenic rats protects motor neurons from death after spinal cord injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2008Article
- Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007Article
- Neuroprotective effect of A20 on TNF-induced postischemic apoptosis.Neurochemical research · 2006Article
- A novel adenoviral vector which mediates hypoxia-inducible gene expression selectively in neurons.Gene therapy · 2005Article
- bcl2, bax, and nestin in the brains of patients with neurodegeneration and those of normal aging.Journal of molecular neuroscience : MN · 2005Article
- Neuroprotective role of a proline-rich Akt substrate in apoptotic neuronal cell death after stroke: relationships with nerve growth factor.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2004Article
- Uptake of liposomally entrapped adenosine-3'-5'-cyclic monophosphate in mouse brain.Neurochemical research · 2004Article
- Transfection of mEpo gene to intestinal epithelium in vivo mediated by oral delivery of chitosan-DNA nanoparticles.World journal of gastroenterology · 2004Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute cerebral ischemia causes hypoxic neuronal cell death by necrosis and apoptosis. Expression of anti-apoptotic transgenes in ischemic brain may provide a useful therapeutic strategy for alleviation of postischemic damage. The present study investigates liposome-mediated transfer of the human bcl-2 protein in a rat model of focal transient ischemia due to middle cerebral artery (MCA) occlusion. Two different types of plasmid vectors were used for bcl-2 expression: one driven by the constitutive cytomegalovirus promoter (pCMV) and another based on the hypoxia-inducible human vascular endothelial growth factor promoter (pHRE). Cationic liposome/plasmid DNA complexes (lipoplexes) were injected directly into the cerebrospinal fluid (CSF) of rats immediately after MCA occlusion. The brains of treated and control animals were analyzed 48 h later. Infarct volumes and numbers of apoptotic cells were quantified. Occlusion of the MCA resulted in ipsilateral cerebral infarcts in all study animals. Transfer of the bcl-2 gene resulted in high level widespread protein expression in the case of the pCMV-bcl2 plasmid, while animals treated with the pHRE-bcl2 vector showed lower expression levels of bcl2 which were in addition limited to the ischemic area. Treatment with pCMV-bcl2, but not with pHRE-bcl2, was able to significantly reduce the infarct volume, which was 109 +/- 8 mm(3) for pCMV-bcl2, 152 +/- 29 mm(3) for pHRE-bcl2, and 155 +/- 18 mm(3) for control animals. Animals transfected with either vector showed a significant reduction in numbers of apoptotic cells in the infarct and penumbra area compared with controls. There were no short-term neurological side-effects of the CSF injection of lipoplexes or of bcl-2 expression. In conclusion, the hypoxia-inducible bcl-2 expression mediated by intrathecal lipoplexes may represent a novel, biologically safe and lesion-selective therapeutic approach for neuroprotection after acute cerebral ischemia. DOI: 10.1038/sj/gt/3301676
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