X-Message-Number: 23794
From: "Basie" <>
Subject: Recovery of postischemic brain 
Date: Fri, 2 Apr 2004 00:53:15 -0500

Recovery of postischemic brain metabolism and function following treatment
with a free radical scavenger and platelet-activating factor antagonists.

Gilboe DD, Kintner D, Fitzpatrick JH, Emoto SE, Esanu A, Braquet PG, Bazan

University of Wisconsin Medical School, Department of Neurosurgery, Madison

We have studied the metabolic and functional effects of two new
platelet-activating factor (PAF) antagonists (BN 50726 and BN 50739) and
their diluent (dimethyl sulfoxide; DMSO) during reoxygenation of the 14-min
ischemic isolated brain. Blood gases, EEG, auditory evoked potentials,
cerebral metabolic rate for glucose (CMRglc), and cerebral metabolic rate
for oxygen (CMRO2) were monitored throughout the study. Frozen brain samples
were taken for measurement of brain tissue high-energy phosphates,
carbohydrate content, and thiobarbituric acid-reactive material (TBAR, an
indicator of lipid peroxidation) at the end of the study. Following 60 min
of reoxygenation in the nontreated 14-min ischemic brains, lactate, AMP,
creatine (Cr), intracellular hydrogen ion concentration [H+]i), and TBAR
values were significantly higher and ATP, creatine phosphate (PCr), CMRglc,
CMRO2, and energy charge (EC) values were significantly lower than the
corresponding normoxic control values. PCr and CMRO2 values were
significantly higher, and glycogen, AMP, and [H+]i values were significantly
lower in the BN 50726-treated ischemic brains than in DMSO-treated ischemic
brains. In brains treated with BN 50739, ATP, ADP, PCr, CMRO2, and EC values
were significantly higher, and lactate, AMP, Cr, and [H+]i values were
significantly lower than corresponding values in the DMSO-treated ischemic
brains. TBAR values were near control levels in all brains exposed to DMSO.
There was also marked recovery of EEG and auditory evoked potentials in
brains treated with DMSO. Treatment with BN 50726 or BN 50739 in DMSO
appeared to improve brain mitochondrial function and energy metabolism
partly as the result of DMSO action as a free radical scavenger.(ABSTRACT

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=23794