TY - JOUR
T1 - Reoxygenation stress on blood-brain barrier paracellular permeability and edema in the rat
AU - Witt, Ken A.
AU - Mark, Karen S.
AU - Sandoval, Karin E.
AU - Davis, Thomas P.
N1 - Funding Information:
This study was supported by funding from the National Institutes of Health, RO1 NS-39592 and F32 NS-43046 (in support of KAW). We also thank Ms. Grace Davis-Gorman for her assistance with our hematological studies.
PY - 2008/1
Y1 - 2008/1
N2 - The blood-brain barrier (BBB) serves as a critical regulator of brain homeostasis. Following hypoxia (i.e. 6% oxygen/1 h) and reoxygenation (H/R), the BBB tight junctional complex is disrupted, resulting in increased BBB permeability and the development of vasogenic brain edema. In this study, we examined the effect of H/R on the in vivo rat BBB over a 36 h time course in conjunction with paracellular permeability, gray matter edema, and systemic inflammatory activity. A biphasic increase was observed in the brain uptake of 14C-sucrose, a paracellular permeability marker; with the first increase at the 10 min reoxygenation time point, and the second increase at the 6-18 h time points. Increased brain water weight gain (edema) also showed a biphasic response with the first increase at the 10 min-1 h reoxygenation time points; and the second increase at only the 24 h time point. Analysis of serum derived cytokines (IL-1β, TNFα, IL-6, IL-10, and IFNγ) demonstrated that only IL-1β and IL-6 were at detectable levels, but these levels were similar to controls. White blood cell counts showed significant decreases in lymphocytes (10 min-3 h), increases in monocytes (10 min-3 h and 12 h), and increases in polymorphonuclear cells (1 h and 3 h). We have shown that H/R elicits a biphasic increase in paracellular permeability and edema, which parallel to post-stroke sequelae, despite the lack of occlusion or complete depletion of oxygen.
AB - The blood-brain barrier (BBB) serves as a critical regulator of brain homeostasis. Following hypoxia (i.e. 6% oxygen/1 h) and reoxygenation (H/R), the BBB tight junctional complex is disrupted, resulting in increased BBB permeability and the development of vasogenic brain edema. In this study, we examined the effect of H/R on the in vivo rat BBB over a 36 h time course in conjunction with paracellular permeability, gray matter edema, and systemic inflammatory activity. A biphasic increase was observed in the brain uptake of 14C-sucrose, a paracellular permeability marker; with the first increase at the 10 min reoxygenation time point, and the second increase at the 6-18 h time points. Increased brain water weight gain (edema) also showed a biphasic response with the first increase at the 10 min-1 h reoxygenation time points; and the second increase at only the 24 h time point. Analysis of serum derived cytokines (IL-1β, TNFα, IL-6, IL-10, and IFNγ) demonstrated that only IL-1β and IL-6 were at detectable levels, but these levels were similar to controls. White blood cell counts showed significant decreases in lymphocytes (10 min-3 h), increases in monocytes (10 min-3 h and 12 h), and increases in polymorphonuclear cells (1 h and 3 h). We have shown that H/R elicits a biphasic increase in paracellular permeability and edema, which parallel to post-stroke sequelae, despite the lack of occlusion or complete depletion of oxygen.
KW - Biphasic
KW - Hypoxia
KW - Oxidative stress
KW - Tight junction
KW - Vasogenic edema
UR - http://www.scopus.com/inward/record.url?scp=37249084760&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37249084760&partnerID=8YFLogxK
U2 - 10.1016/j.mvr.2007.06.004
DO - 10.1016/j.mvr.2007.06.004
M3 - Article
C2 - 17651765
AN - SCOPUS:37249084760
SN - 0026-2862
VL - 75
SP - 91
EP - 96
JO - Microvascular Research
JF - Microvascular Research
IS - 1
ER -