Effect of reduced flow on blood-brain barrier transport systems.
Pathological states (i.e. stroke, cardiac arrest) can lead to reduced blood flow to the brain potentially altering blood-brain barrier (BBB) permeability and regulatory transport functions. BBB disruption leads to increased cerebrovascular permeability, an important factor in the development of ischemic brain injury and edema formation. In this study, reduced flow was investigated to determine the effects on cerebral blood flow (CBF), pressure, basal BBB permeability, and transport of insulin and K+ across the BBB. Anesthetized 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 autoregulation remained functional. In contrast, there was a concomittant decrease in BBB transport of both insulin and K+ with reduced flow. At half and quarter flow, insulin transport was significantly reduced (R(Br)%=17.2 and R(Br)%=16.2, respectively) from control (R(Br)%=30.4). Additionally, a significant reduction in [86Rb+] 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 result of low flow. This investigation suggests that although autoregulation maintains CBF, BBB transport mechanisms were significantly compromised in states of reduced flow. These flow alterations may have a significant impact on brain homeostasis in pathological states.
Hom
S
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Department of Pharmacology, University of Arizona, College of Medicine, Tucson, AZ 85724, USA.
Egleton
R D
RD
Huber
J D
JD
Davis
T P
TP
D000818:Animals; D001784:Blood Gas Analysis; D001812:Blood-Brain Barrier / Q000502:physiology*; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007328:Insulin / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes; D020521:Stroke / Q000378:metabolism; D013395:Sucrose / Q000493:pharmacokinetics
D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D012414:Rubidium Radioisotopes; D013395:Sucrose; D011188:Potassium