Journal
NEUROSURGERY
Volume 52, Issue 2, Pages 402-412Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1227/01.NEU.0000043698.86548.A0
Keywords
blood-brain barrier; cellular neurosurgery; delivery; endovascular; gene therapy; intra-arterial; molecular neurosurgery; neurorestoration; stem cells
Categories
Ask authors/readers for more resources
THE AMALGAM OF molecular biology and neurosurgery offers immense promise for neurorestoration and the management of neurodegenerative deficiencies, developmental disorders, neoplasms, stroke, and trauma. This article summarizes present strategies for and impediments to gene therapy and stem cell therapy of the central nervous system and advances the concept of a potential new approach, namely endovascular restorative neurosurgery. The objectives of gene, transfer to the central nervous system are efficient transfection of host cells, selective sustained expression,of the transgene, and lack of toxicity or immune excitation. The requisite elements of this process are the identification of candidate diseases, the construction of vehicles for gene transfer, regulated expression, and physical delivery. In the selection of target, disorders, the underlying genetic events to be overcome, as well as their spatial and temporal distributions, must be considered. These factors determine the requirements for the physical dispersal of the transgene, the duration of transgene expression, and, the quantity of transgene product needed to abrogate the disease phenotype. Vehicles for conveying the transgene to the central nervous system include viral, vectors' (retroviruses, lentiviruses, adenoviruses, adeno-associated viruses, and herpes simplex De-virus), liposomes, and genetically engineered cells, including neural stem cells. livery of the transgene into the brain presents several challenges, including limited and potentially risky access through the cranium, sensitivity to volumetric changes,restricted diffusion, and the blood-brain barrier. Genetic or cellular therapeutic agents may be injected directly into the brain parenchyma (via stereotaxy or craniotomy), into the cerebrospinal fluid (in the ventricles or cisterns), or into the bloodstream (intravenously or intra-arterially). The advantages of the endovascular route include the potential for widespread distribution, the ability to deliver large volumes, limited perturbation of neural tissue, and the feasibility of repeated administration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available