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| INHIBITION OF BRAIN GLUTAMINE ACCUMULATION PREVENTS CEREBRAL EDEMA IN HYPERAMMONEMIC RATS |
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| Author(s): TAKAHASHI H, KOEHLER RC, BRUSILOW SW, TRAYSTMAN RJ |
| Source: AMERICAN JOURNAL OF PHYSIOLOGY Volume: 261 Issue: 3 Pages: H825-H829 Part: Part 2 Published: SEP 1991 |
| Times Cited: 130 References: 36 |
| Abstract: The mechanism of brain swelling during hyperammonemia is not understood, but glutamine accumulation is consistently observed. We tested the hypothesis that brain swelling associated with hyperammonemia is a consequence of the osmotic effect of intracellular glutamine accumulation in brain. Increases in plasma ammonium levels from 31 +/- 3 to 601 +/- 38-mu-mol/l (+/- SE) were produced by 6 h of infusion of ammonium acetate in anesthetized rats. Hyperammonemia resulted in increased brain water content accompanied by more than a tripling of brain glutamine concentration compared with control rats receiving sodium acetate (5.6 +/- 0.4 vs. 18.8 +/- 0.4 mmol/kg). Inhibition of glutamine synthetase activity by pretreatment with L-methionine sulfoximine prevented both the increase in brain glutamine levels and the increase in brain water content despite elevated plasma ammonium levels (908 +/- 196-mu-mol/l). Thus cerebral edema during hyperammonemia is associated with glutamine accumulation. We suggest that accumulated glutamine may serve as an idiogenic osmole causing swelling. Because brain swelling eventually leads to increased intracranial pressure and tissue hypoxia, these data suggest a unifying mechanism to account for the many pathophysiological abnormalities found during coma associated with various forms of liver disease, inborn errors of metabolism, and Reye's syndrome. |
| Document Type: Article |
| Language: English |
Addresses:
1. JOHNS HOPKINS MED INST, DEPT ANESTHESIOL CRIT CARE MED, 600 N WOLFE ST, BALTIMORE, MD 21205 USA
2. JOHNS HOPKINS MED INST, DEPT PEDIAT, BALTIMORE, MD 21205 USA |
| Publisher: AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Physiology |
| IDS Number: GE638 |
| ISSN: 0002-9513 |
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