Gene transfer to cerebral vessels during vasospasm using recombinant adenovirus

Muhonen, M.G., Martin, D.G., Heistead, D.D., and Welsch, M.J. (1995) Gene transfer to cerebral vessels during vasospasm using recombinant adenovirus. Journal of Neurology, Neurosurgery, and Psychiatry, 60 (2). p. 245.

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Vasospasm remains a major cause of morbidity and mortality after aneurysmal subarachnoid haemorrhage. Preliminary feasibility studies of gene therapy were explored using a viral vector to prevent spasm of cerebral vessels by transducing a reporter gene into cerebral vessels. Vasospasm was induced in mongrel dogs (n= 6) using the double haemorrhage intracisternal injection model. Basilar artery diameter was assessed by angiography and profound vasospasm was confirmed at four and seven days. Recombinant adenovirus(1-2-3-8 x 101" infectious units) expression nuclear-targeted IacZ (reporter gene) under the control of the cytomegalovirus promoter was injected intracisternally at the same time as the induction of vasospasm in eight separate animals. The brains were removed and histochemically examined by staining for nuclear, B-galactosidase. At two to seven days, ,B-galactosidase was expressed in leptomeninges over the brain stem, cortex, cerebral arteries, in small vessels in the cerebellum and brain stem, and in the ependymal lining of the ventricles. Gene transduction occurred within the adventitia of blood vessels, but none was observed in the smooth muscle or endolithium of the vessels. The findings indicate that intracisternal injection of the recombinant adenovirus can be used for gene transfer to cerebral vessels and overlying meninges, even in the presence of cisternal blood and vasospasm. Transfer and expression of genes that encode for enzymes with vasodilator function(especially highly diffusible substances such as nitric oxide synthase) to cerebral blood vessels using recombinant viral vectors may be useful for prevention or treatment of cerebral vasospasm.

Item ID: 48318
Item Type: Article (Abstract)
ISSN: 0022-3050
Keywords: gene transfer; cerebral vessels; vasospasm
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Proceedings of the second meeting of the British Neurosurgery Research Group, Chollerford, Northumberland, 20-2 1 April 1995

Date Deposited: 02 May 2017 01:31
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920110 Inherited Diseases (incl. Gene Therapy) @ 100%
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