The Effect of a Low pH Saline Perfusate upon the Integrity of the Energy-Depleted Rat Blood-Brain Barrier

The effect of a low pH perfusate upon the integrity of the rat blood-brain barrier was studied using an in situ supravital brain perfusion technique in which high-energy phosphates are depleted. Control animals were perfused for 10 min with a Ringer's salt solution containing the metabolic inhibitor 2,4-dinitrophenol (DNP) and adjusted to a pH of 7.4. In two separate experimental groups the perfusate, consisting of either the same medium as the controls or with additional buffering from Tris maleate, was switched after 5 min at a pH of 7.4, to a medium adjusted to pH 5.5 with lactic acid. Following a total perfusion time of 10 min, the integrity of the blood-brain barrier was assessed using the small molecular weight tracer [14C]mannitol. The cerebral perfusate flow rates (CPFR) after 10 min of perfusion were also determined in the three groups by perfusing for 40 s with [14C]iodoantipyrine. In each group, mannitol was excluded from the tissue of the brain to the same degree as has been previously reported in vivo, indicating an intact blood-brain barrier. There was also no significant pH-dependent change in CPFR. Ultrastructural examination of animals that had been perfusion fixed following in situ perfusion revealed no obvious differences between the cerebral endothelium of the control and low pH perfused animals. These results demonstrate that in the absence of energy-producing metabolism a perfusate pH of 5.5 is insufficient to disrupt the blood-brain barrier.

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The Effect of Bile Salts on the Permeability and Ultrastructure of the Perfused, Energy-Depleted, Rat Blood-Brain Barrier

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1991.116 ◽

1991 ◽

Vol 11 (4) ◽

pp. 644-654 ◽

Cited By ~ 41

Author(s):

J. Greenwood ◽

J. Adu ◽

A. J. Davey ◽

N. J. Abbott ◽

M. W. B. Bradbury

Keyword(s):

Blood Brain Barrier ◽

Bile Salts ◽

Structural Changes ◽

Sodium Deoxycholate ◽

Ringer Solution ◽

Brain Barrier ◽

Rat Blood ◽

Blood Brain ◽

Ultrastructural Damage

The action of bile salts upon the rat blood–brain barrier (BBB) was assessed in the absence of energy-yielding metabolism. Brains were perfused in situ with a Ringer solution for 5 min followed by a 1 min perfusion containing either sodium deoxycholate (DOC), taurochenodeoxycholate (TCDC), or Ringer/DNP. The integrity of the BBB was then determined by perfusing with the radiotracer [14C]mannitol for 2.5 min. Alternatively, the brains were perfusion fixed for ultrastructural assessment. At 0.2 m M DOC, the BBB remained intact and the cerebral ultrastructure was similar to the controls. At 1 m M and above, disruption of the BBB became evident. At 2 m M, the cerebral cortex became severely vacuolated, with damaged endothelium and collapsed capillaries. With TCDC, BBB disruption occurred at 0.2 m M without any apparent ultrastructural damage to the micro vasculature. Following 2 m M TCDC, similar, but less widespread, structural changes to the 2 m M DOC-perfused animals was apparent. Opening of the BBB occurred at a concentration lower than that required to cause lysis of either red blood cells or cultured cerebral endothelial cells. It is proposed that the effect of bile salts at concentrations of 1.5 m M and above is largely due to their lytic action as strong detergents on endothelial cell membranes, but that at lower concentrations a more subtle modification of the BBB occurs.

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The Transendothelial DC Potential of Rat Blood-Brain Barrier Vessels in Situ

Frontiers in Cerebral Vascular Biology - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4615-2920-0_12 ◽

1993 ◽

pp. 71-74 ◽

Cited By ~ 11

Author(s):

Patricia A. Revest ◽

Hazel C. Jones ◽

N. Joan Abbott

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Rat Blood ◽

Blood Brain ◽

Dc Potential

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Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.252.3.h504 ◽

1987 ◽

Vol 252 (3) ◽

pp. H504-H512 ◽

Cited By ~ 5

Author(s):

T. Beck ◽

J. Krieglstein

Keyword(s):

White Matter ◽

Blood Brain Barrier ◽

Gray Matter ◽

Cerebral Circulation ◽

High Energy ◽

Brain Barrier ◽

High Energy Phosphates ◽

Glucose Content ◽

Physiological Variables ◽

Blood Brain

The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O2. Hypoxia affected a marked hypotension, hypocapnia, and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate, lactate, and pyruvate levels were significantly increased. Blood-brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40–70% of control values in gray matter and by 80–90% in white matter. Under hypoxia, columns of increased and decreased LCGU were detectable in cortical gray matter. Local cerebral blood flow (LCBF) increased by 50–90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggest a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur.

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