Effect of steroid therapy on ischaemic brain oedema and blood to brain sodium transport.
Dexamethasone has been shown in some studies to reduce ischaemic brain oedema, however, the mechanism is unknown. One possible mechanism is through inhibition of active transport of sodium across the blood-brain barrier (BBB) since some steroids, especially progesterone, inhibit sodium transport in isolated brain capillaries. Therefore, we measured brain oedema and BBB permeability to sodium and a passive permeability tracer, alpha-aminoisobutyric acid (AIB), 4 hr after middle cerebral artery occlusion (MCAO) in rats that had been treated 1 hr before MCAO with vehicle (control) or 2 mg/kg of either dexamethasone or progesterone. In controls, the water content of tissue in the center of the ischaemic zone was 82.4 +/- 0.2%. Brain oedema was significantly reduced following pretreatment with either dexamethasone (80.6 +/- 0.1, p less than 0.001) or progesterone (81.5 +/- 0.3, p less than 0.05). Both steroids also reduced BBB permeability to AIB by about 40% in normal brain but to a lesser extent in ischaemic brain. In contrast, steroid treatment had no effect on BBB permeability to sodium in either normal or ischaemic brain. We conclude that pretreatment with dexamethasone and progesterone reduces brain oedema accumulation during the early stages of ischaemia, however, this effect does not result from a reduction in BBB permeability to sodium.
Betz
A L
AL
Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor.
Coester
H C
HC
D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology*; D002545:Brain Ischemia / Q000097:blood / Q000150:complications* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D008297:Male; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood / Q000378:metabolism*
D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; D011374:Progesterone; D003907:Dexamethasone; D012964:Sodium