Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means.
OBJECTIVE
This article reviews historical aspects of the blood-brain barrier (BBB) and recent advances in mechanisms to deliver therapeutic agents across the BBB for the treatment of intracerebral tumors and other neurological diseases.


METHODS
The development of the osmotic BBB disruption procedure as a clinically useful technique is described. Osmotic BBB disruption is contrasted with alternative methods for opening or bypassing the BBB, including pharmacological modification of the BBB with bradykinin and direct intracerebral infusion.


RESULTS
Laboratory studies have played a fundamental role in advancing our understanding of the BBB and delivery of agents to brain. Preclinical animal studies will continue to serve an integral function in our efforts to improve the diagnosis and treatment of a number of neurological disorders. Techniques involving the modification of the BBB and/or blood-tumor barrier to increase delivery of therapeutic agents have been advanced to clinical trials in patients with brain tumors with very favorable results.


CONCLUSIONS
Improving delivery of agents to the brain will play a major role in the therapeutic outcome of brain neoplasms. As techniques for gene therapy are advanced, manipulation of the BBB also may be important in the treatment of central nervous system genetic disorders.
Kroll
R A
RA
Department of Neurology, Oregon Health Sciences University, Portland 97201, USA.
Neuwelt
E A
EA
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology / Q000532:radiotherapy / Q000628:therapy; D017321:Clinical Trials, Phase I as Topic; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D016371:Cranial Irradiation / Q000009:adverse effects; D004285:Dogs; D005544:Forecasting; D015316:Genetic Therapy; D034381:Hearing Loss / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D000922:Immunotoxins / Q000493:pharmacokinetics; D015993:Life Tables; D016464:Lysosomal Storage Diseases / Q000628:therapy; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology; D009997:Osmotic Pressure; D010300:Parkinson Disease / Q000628:therapy; D010599:Pharmacokinetics; D011788:Quality of Life; D051381:Rats; D011923:Rats, Nude; D016019:Survival Analysis
D000970:Antineoplastic Agents; D006982:Hypertonic Solutions; D000922:Immunotoxins; D008353:Mannitol; D001920:Bradykinin