H. Soreq1, D. Kaufer1, I. Shelef2, H. Golan3, O.Tomkins4, Y. Hertzanu2, D. Glick1 E. Reichenthal4 and A Friedman4
1The Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Israel
Departments of 2Radiology, 3Nuclear Medicine and 4Neurosurgery, Ben-Gurion University, Beersheva, 84105 Israel

Separation of the brain from the peripheral blood is crucial for protecting it from circulating xenobiotic agents, yet must allow for nutrition of the brain and removal of waste products. The blood-brain barrier (BBB) is an endothelial tissue that hinders the entry of most hydrophilic xenobiotics into the brain, and exports such substances from the brain when they do enter it. The physical and functional complexity of the BBB has hampered research efforts to delineate its components and fully understand its mode of action. Recent use of transgenic engineering approaches has revealed a cascade of events that result in modulation of BBB functioning. Impairment of any element of this chain of factors can disrupt BBB properties, but the extent and duration of such disruption apparently depends on the genetics, health and wellbeing of the subject. In a retrospective survey for clinical correlates of BBB disruption, we analyzed computerized tomography (CT), single photon emission CT (SPECT) and magnetic resonance imaging (MRI) brain images of neurological patients. Focal or diffused enhancement of contrast agent signals, reflecting BBB disruption, occurred frequently in the cerebral cortex. Patients with BBB disruption also presented significantly higher stress-related clinical indices (e.g. cortisol and systolic blood pressure) than those with an intact BBB. In the cerebrospinal fluid, albumin accumulation as well as conspicuous levels of the stress-associated isoform of acetylcholinesterase, AChE-R, correlated with CT signal enhancement. Our findings suggest that persistent, compromised BBB may accompany the wide range of clinical conditions associated with stress responses. (Supported by The Israel Science Foundation, 590/97; the US Army Medical Research and Materiel Command, DAMD17-99-1-9483; and Ester Neuroscience, Ltd.)