How inflammation modulates central nervous system vessel activation and provides targets for intervention--a personal perspective.
I here describe a line of research that grew out of studies of spinal cord-damaging decompression sickness, focused on the blood-endothelial interface, that was influenced by the local Shwartzman phenomenon, addressed innate immune and inflammatory mechanisms, and ultimately arrived at mucosal tolerance approaches to prevent stroke. Intranasal instillation of E-selectin is under development as a novel means of targeting immunomodulation to activating blood vessels within the vascular tree supplying the brain. The goal of this form of focused immunomodulation is to prevent recurrent strokes in patients that have previously suffered transient ischemic attacks or strokes.
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. hallenbj@ninds.nih.gov
John
J
Hallenbeck
D000818:Animals; D002490:Central Nervous System / Q000098:blood supply* / Q000503:physiopathology*; D019040:E-Selectin / Q000008:administration & dosage; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D051381:Rats; D012790:Shwartzman Phenomenon / Q000503:physiopathology; D020521:Stroke / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha