Gene Therapy for Cerebrovascular Disease

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Abstract
To review the principles of and the experimental and clinical results of gene therapy for cerebrovascular disease. Literature review. Vectors for gene transfer into the brain or into the cerebral vasculature include naked plasmid deoxyribonucleic acid, cationic liposomes, and viruses such as adenovirus, retrovirus, adeno-associated virus, and herpes simplex virus. Experiments using these vectors showed that intra- or perivascular application to systemic arteries can lead to transfection and expression of a foreign transgene in the adventitia and the endothelium. Intrathecal administration can lead to transfection and foreign transgene expression in leptomeningeal cells as well as in fibroblasts of blood vessel adventitia. Biological effects demonstrated thus far include increased nitric oxide production by transfection of cerebral arterial adventitia with adenovirus expressing nitric oxide synthase. Adenoviruses carrying foreign genes have been used to decrease neuronal damage in cerebral ischemia and to decrease blood pressure in spontaneously hypertensive rats. Vectors and therapeutic applications for gene therapy are evolving rapidly. Gene therapy for cerebrovascular disease is likely to have clinical application in the near future and will have a major impact on neurosurgery. Neurosurgeons will need to be aware of the literature in this area.