Astrocytic swelling in traumatic-hypoxic brain injury. Beneficial effects of an inhibitor of anion exchange transport and glutamate uptake in glial cells.
Swelling of brain slices is shown to occur in response to elevated potassium levels or glutamate, which is accompanied by astrocytic swelling. Cl-/HCO3- anion exchange inhibitors, such as SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid) or furosemide, but not the specific cotransport inhibitor bumetanide, inhibit swelling or increased ion uptake in rat brain slices caused by elevated potassium although there were marked species differences in sensitivity. A novel anion exchange inhibitor, L-644,711, inhibits swelling and increased ion uptake caused by glutamate in rat and cat brain slices, as well as inhibiting [3H]glutamate uptake in primary rat astrocyte cultures. Possible mechanisms of action of the inhibitors are discussed. L-644,711 was also found to be effective in promoting recovery from a trauma plus hypoxia head injury model in cats. Marked perivascular astrocytic swelling is associated with this head injury model, and L-644,711 also inhibited such astroglial swelling as determined ultrastructurally. The significance of these findings in relation to possible connections between astrocytic swelling and brain pathology is discussed.
Kimelberg
H K
HK
Division of Neurosurgery, New York State Department of Health, Albany 12208.
Rose
J W
JW
Barron
K D
KD
Waniewski
R A
RA
Cragoe
E J
EJ
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001692:Biological Transport; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology*; D002415:Cats; D002478:Cells, Cultured; D002712:Chlorides / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005449:Fluorenes / Q000627:therapeutic use; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000473:pathology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats
D002712:Chlorides; D005449:Fluorenes; D005971:Glutamates; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D018698:Glutamic Acid; D010042:Ouabain; D011188:Potassium; C053396:L 644711