Effect of reduced flow on blood-brain barrier transport systems

Pathological states (i.e. stroke, cardiac arrest) can lead to reduced blood Row to the brain potentially altering blood-brain barrier (BBB) permeabili ty and regulatory transport functions. BBB disruption leads to increased ce rebrovascular permeability, an important factor in the development of ische mic brain injury and edema formation. In this study, reduced flow was inves tigated to determine the effects on cerebral blood flow (CBF), pressure, ba sal BBB permeability, and transport of insulin and K+ across the BBB. Anest hetized adult female Sprague-Dawley rats were measured at normal flow (3.1 ml min(-1)), half flow (1.5 ml min(-1)), and quarter flow (0.75 ml min(-1)) , using bilateral in situ brain perfusion for 20 min followed by capillary depletion analysis. Reduction in perfusion flow rates demonstrated a modest reduction in CBF (1.27-1.56 ml min(-1) g(-1)), a decrease in pressure, and no significant effect on basal BBB permeability indicating that autoregula tion remained functional. In contrast, there was a concomittant decrease in BBB transport of both insulin and K+ with reduced flow. At half and quarte r flow, insulin transport was significantly reduced (R-Br%=17.2 and R-Br%=1 6.2, respectively) from control (R-Br%=30.4). Additionally, a significant r eduction in [Rb-86(+)] was observed at quarter flow (R-Br%=2.5) as compared to control (R-Br%=4.8) suggesting an alteration in ion homeostasis as a re sult of low flow. This investigation suggests that although autoregulation maintains CBF, BBB transport mechanisms were significantly compromised in s tates of reduced flow. These flow alterations may have a significant impact on brain homeostasis in pathological states. (C) 2001 Elsevier Science B.V . All rights reserved.