Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin.

Abstract

The present study was undertaken to analyze the roles of brain cations and of the blood-brain barrier (BBB) to albumin in the development of ischemic brain edema. Using the rat middle cerebral artery (MCA) occlusion model, changes in the brain water, sodium, and potassium contents were followed for a period of seven days. The permeability of the BBB to proteins was also followed by 125I-albumin transfer from the blood into the brain. A significant edema developed as early as three hours after MCA occlusion. This progressed rapidly to reach a maximum on the third day, gradually regressing thereafter. The increase in the brain water contents showed a parallel time course to the increase in the sodium and decrease in the potassium contents. A significant increase in the BBB permeability to albumin occurred 72 hours after MCA occlusion. However, there was no correlation between the brain water content and BBB permeability to albumin in the hemispheres studied 72 hours after MCA occlusion. The correlation between the brain water and sodium contents was not clear during the first six hours, but became highly significant thereafter. The data suggest that an increase in the BBB permeability to sodium occurred 12-48 hours after MCA occlusion, which, together with an antecedent intracellular shift of sodium, resulted in a massive influx of water and sodium into the brain. The BBB permeability change to sodium, not to proteins, seems to play a predominant role in the pathogenesis underlying ischemic brain edema.

The Protein Kinase C Activator Phorbol Myristate Acetate Decreases Brain Edema by Aquaporin 4 Downregulation after Middle Cerebral Artery Occlusion in the Rat

“…Although PMA slightly blunted the potassium loss associated with brain edema, this effect failed to reach statistical significance. These findings are consistent with the generally-accepted opinion that water and sodium tend to coexist, and move together through the plasma membrane under physiological and pathological conditions (Gotoh et al, 1985;Loo et al, 1996;Wright and Loo, 2000). Alternatively, in addition to the blunting of AQP4 upregulation by PMA, brain sodium channels may have been independently affected (Hourez et al, 2005).…”

Bumetanide Inhibition of the Blood-Brain Barrier Na-K-Cl Cotransporter Reduces Edema Formation in the Rat Middle Cerebral Artery Occlusion Model of Stroke

“…Brain edema that forms during the early hours of ischemic stroke involves a net uptake of Na + and water from blood into brain across an intact blood-brain barrier (BBB) (Betz, 1996;Betz et al, 1994Betz et al, , 1995Menzies et al, 1990Menzies et al, , 1993Schielke et al, 1991) along with swelling of astrocytes (Bourke et al, 1980;Gotoh et al, 1985;Iadecola, 1999;Kempski et al, 1991;Kimelberg, 1995Kimelberg, , 1999. Previous studies have shown that BBB breakdown, allowing paracellular flux of solute and water into the brain, generally occurs after 3 to 6 hours of continuous reduction in blood flow, and that the majority of edema formation is accounted for by the net uptake of brain cations and water that occurs well before BBB breakdown (Betz, 1996).…”

Identification and quantitative analysis of hydroxy-eicosatetraenoic acids in rat brains exposed to regional ischemia.

“…This model is known to provide a reproducible and consistent lesion assessed by regional cerebral blood flow and the extent of the ischemic area. 13>25 We analyzed the time course of edema formation in the ischemic hemisphere of this model, 26 and we measured HETEs 24 hours after MCA occlusion, when the edema was progressing most rapidly, and at 72 hours, when the edema reached its maximum. In the brain rendered ischemic for 72 hours, the amounts of all 6 HETEs were increased, and the increases in 5-, 9-, 11-, and 15-HETE were significant.…”