Endovascular restorative neurosurgery: A novel concept for molecular and cellular therapy of the nervous system

Arun Paul Amar, Berislav V. Zlokovic, Michael L.J. Apuzzo, Edward A. Neuwelt, Joseph M. Piepmeier, Robert G. Grossman, Bernard R. Bendok, L. Nelson Hopkins

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


THE AMALGAM OF molecular biology and neurosurgery offers immense proriise 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 vehi(les 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 virus), liposomes, and genetically engineered cells, including neural stem cells. Delivery 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 (irtravenously or intra-arterially). The advantages of the endovascular route inclu(e the potential for widespread distribution, the ability to deliver large volumes, limited perturbation of neural tissue, and the feasibility of repeated administration.

Original languageEnglish (US)
Pages (from-to)402-413
Number of pages12
Issue number2
StatePublished - Feb 1 2003


  • Blood-brain barrier
  • Cellular neurosurgery
  • Delivery
  • Endovascular
  • Gene therapy
  • Intraarterial
  • Molecular neurosurgery
  • Neurorestoration
  • Stem cells

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery


Dive into the research topics of 'Endovascular restorative neurosurgery: A novel concept for molecular and cellular therapy of the nervous system'. Together they form a unique fingerprint.

Cite this