Brain ischemia augments exo-focal transgene expression of adenovirus-mediated gene transfer to ependyma in hypertensive rats

Kumai, Yasuhiro; Ooboshi, Hiroaki; Kitazono, Takanari; Takada, Junichi; Ibayashi, Setsuro; Fujishima, Masatoshi; Iida, Mitsuo

doi:10.1016/j.expneurol.2003.08.022

Cited by 9 publications

(11 citation statements)

References 35 publications

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“…Previous studies showed that other viral vectors administered intrathecally induced transgene expression in, not further characterized, cells lining the ventricular ependyma. 56,57 We identified that i.c.v. administration of LV vectors particularly transduced macrophages lining the ventricular walls and in the meninges, as identified by immunohistochemical double labelling with ED1, a marker for macrophages.…”

Section: Cellular Localization Of Gfp Ril-10 and Ril-1ra In Vivo Aftmentioning

confidence: 99%

Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages

et al. 2010

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Section: Cellular Localization Of Gfp Ril-10 and Ril-1ra In Vivo Aftmentioning

confidence: 99%

Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages

et al. 2010

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“…Four slices that contained lateral ventricles in each rat were examined for positive staining of ␤-galactosidase (blue staining) in the macroscopic view. Expression of ␤-galactosidase in the left ventricle was analyzed semiquantitatively, and estimated with a four-point scale (0 ‫ס‬ no stain, 1 ‫ס‬ modest or approximately 1% to 25% area of stained blue in the ventricular wall, 2 ‫ס‬ moderate or 26% to 75% area of stained blue in the ventricular wall, and 3 ‫ס‬ marked or >75% area of stained blue in the ventricular wall) as described previously (Kumai et al, 2003;Ooboshi et al, 2001). The scores of four slices were averaged and used as expression score.…”

Section: Histochemical Analysis Of Gene Expressionmentioning

confidence: 99%

“…To rationalize gene therapy for brain ischemia, it is important to show efficacy of gene transfer even when vectors are administered after induction of brain ischemia. We have recently shown that gene transfer can be accomplished after induction of brain ischemia either to brain parenchyma or ventricular walls (Ooboshi et al, 2001;Takada et al, 2002;Kumai et al, 2003).…”

mentioning

confidence: 99%

Anti—Monocyte Chemoattractant Protein-1 Gene Therapy Protects against Focal Brain Ischemia in Hypertensive Rats

Kumai

Ooboshi

Takada

et al. 2004

J Cereb Blood Flow Metab

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Summary:Monocyte chemoattractant protein-1 (MCP-1) is expressed in the ischemic cortex after focal brain ischemia and appears to exacerbate ischemic damage. The authors examined the effect of gene transfer of dominant negative MCP-1, called 7ND, 90 minutes after induction of focal brain ischemia in hypertensive rats. Adenoviral vectors encoding mutant MCP-1 (Ad7ND; n ‫ס‬ 11), or Escherichia coli ␤-galactosidase (AdlacZ; n ‫ס‬ 17) as control were injected into the lateral ventricle of male spontaneously hypertensive rats. Both AdlacZ (n ‫ס‬ 12) and Ad7ND (n ‫ס‬ 6) administration provided transgene expression as early as 6 hours after injection and the expression further increased on day 1, followed by a sustained detection on day 5. Five days after ischemia, infarct volume (75 ± 13 mm 3 , n ‫ס‬ 5, mean ± SD) significantly reduced to 72% of control (104 ± 22 mm 3 , n ‫ס‬ 5, P < 0.05) by 7ND gene transfer. Numbers of leukocytes in the vessels (48.3 ± 32.9/cm 2 ) and macrophage/monocyte infiltration (475.2 ± 125.5 /mm 2 ) of the infarct area in the Ad7ND group were significantly less than those measured in the AdlacZ group (143.8 ± 72.1/cm 2 and 671.8 ± 125.5/mm 2 , P < 0.05, respectively). In summary, the postischemic gene transfer of dominant negative MCP-1 attenuated the infarct volume and infiltration of inflammatory cells, suggesting potential usefulness of the anti-MCP-1 gene therapy.

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“…Reporter gene expressions confirm that viruses efficiently transmit exogenous DNA to CSF-bordering regions (Table I) as well as large vessel adventitia (195,196); the latter indicates feasible gene targeting to VirchowYRobin spaces. Ependymal expression of b-glucuronidase (deficient in lysosomal storage disease) occurs after intraventricular gene transfer via a viral vector (197).…”

Section: Gene Transfer With Intraventricular and Intrathecal Vectorsmentioning

confidence: 67%

Enhanced Prospects for Drug Delivery and Brain Targeting by the Choroid Plexus–CSF Route

et al. 2005

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The choroid plexus (CP), i.e., the blood-cerebrospinal fluid barrier (BCSFB) interface, is an epithelial boundary exploitable for drug delivery to brain. Agents transported from blood to lateral ventricles are convected by CSF volume transmission (bulk flow) to many periventricular targets. These include the caudate, hippocampus, specialized circumventricular organs, hypothalamus, and the downstream pia-glia and arachnoid membranes. The CSF circulatory system normally provides micronutrients, neurotrophins, hormones, neuropeptides, and growth factors extensively to neuronal networks. Therefore, drugs directed to CSF can modulate a variety of endocrine, immunologic, and behavioral phenomema; and can help to restore brain interstitial and cellular homeostasis disrupted by disease and trauma. This review integrates information from animal models that demonstrates marked physiologic effects of substances introduced into the ventricular system. It also recapitulates how pharmacologic agents administered into the CSF system prevent disease or enhance the brain's ability to recover from chemical and physical insults. In regard to drug distribution in the CNS, the BCSFB interaction with the blood-brain barrier is discussed. With a view toward translational CSF pharmacotherapy, there are several promising innovations in progress: bone marrow cell infusions, CP encapsulation and transplants, neural stem cell augmentation, phage display of peptide ligands for CP epithelium, CSF gene transfer, regulation of leukocyte and cytokine trafficking at the BCSFB, and the purification of neurotoxic CSF in degenerative states. The progressively increasing pharmacological significance of the CP-CSF nexus is analyzed in light of treating AIDS, multiple sclerosis, stroke, hydrocephalus, and Alzheimer's disease.

show abstract

Brain ischemia augments exo-focal transgene expression of adenovirus-mediated gene transfer to ependyma in hypertensive rats

Cited by 9 publications

References 35 publications

Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages

Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages

Anti—Monocyte Chemoattractant Protein-1 Gene Therapy Protects against Focal Brain Ischemia in Hypertensive Rats

Enhanced Prospects for Drug Delivery and Brain Targeting by the Choroid Plexus–CSF Route

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