X-Message-Number: 15771
Date: Wed, 28 Feb 2001 23:58:11 -0800 (PST)
From: Doug Skrecky <>
Subject: dramatic protection of brain slices with fructose-1,6-bisphosphate

Title
  Fructose-1,6-bisphosphate preserves adenosine
  triphosphate but not intracellular pH during hypoxia in
  respiring neonatal rat brain slices.
Source
  Anesthesiology.  88(2):461-72, 1998 Feb.
Abstract
  BACKGROUND: Fructose-1,6-bisphosphate (FBP) sometimes
  provides substantial cerebral protection during hypoxia or ischemia. 31P/1H
  nuclear magnetic resonance spectroscopy of cerebrocortical slices was used to
  study the effects of FBP on hypoxia-induced metabolic changes. In addition,
  13C-labeled glucose was administered and 13C nuclear magnetic resonance
  spectroscopy was used to search for FBP-induced modulations in glycolysis and
  the pentose-phosphate pathway. METHODS: In each experiment,
  80 slices (350 microm) obtained from ten 7-day-old Sprague-Dawley rat litter
  mates were placed together in a 20-mm nuclear magnetic resonance tube,
  perfused, and subjected to 30 min of hypoxia (PO2 < 3 mmHg). Nine experiments
  were performed, with n = 3 in each of three groups: (1) no treatment with
  FBP; (2) 60 min of prehypoxia treatment with FBP (2 mM); and (3) 60 min of
  posthypoxia treatment with FBP (2 mM). 31P/1H Interleaved nuclear magnetic
  resonance spectra at 4.7 T provided average adenosine
  triphosphate, intracellular pH, and lactate. Cresyl violet
  stains of random slices taken at predetermined time points were studied
  histologically. Some experiments had [2-13C]glucose in the perfusate. Slices
  from these studies were frozen for perchloric acid extraction of
  intracellular metabolites and studied with high-resolution 13C nuclear
  magnetic resonance spectroscopy at 11.75 T. RESULTS: With no pretreatment
  with FBP, hypoxia caused an approximately 50% loss of adenosine
  triphosphate, an approximately 700% increase in lactate, and
  a decrease in intracellular pH to approximately 6.4. Pretreatment with FBP
  resulted in no detectable loss of adenosine triphosphate, no
  increase in lactate, and minimal morphologic changes but did not alter
  decreases in intracellular pH. 13C Nuclear magnetic resonance spectra of
  extracted metabolites showed that pretreatment caused accumulation of
  [1-13C]fructose-6-phosphate, an early
  pentose-phosphate pathway metabolite. Posthypoxic treatment
  with FBP had no effects compared with no treatment. CONCLUSIONS: During
  severe hypoxia, pretreatment with FBP completely preserves adenosine
  triphosphate and almost completely preserves cell morphology
  but does not alter hypoxia-induced decreases in intracellular pH.
  Pretreatment also substantially augments the flux of glucose into the
  pentose-phosphate pathway.

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