Effect of dexamethasone on blood‐brain barrier in the normal mouse

Abstract

Dexamethasone ameliorates cerebral edema, but its effect on normal blood-brain barrier is unknown, as is the site of action. Sixteen normal mice were given dexamethasone, 3 mg/kg intramuscularly or 2 mg/kg intravenously. One to two hours later 10 mg of horseradish peroxidase (HRP) in 0.1 ml of saline was administered intravenously and allowed to circulate for 15 minutes. Brain slices were examined by light and electron microscopy. The number of HRP-permeable arteriolar segments per brain was less in dexamethasone-treated than in control mice (p less than 0.001). In addition, the number of small HRP-filled endothelial vesicles of capillaries and of HRP-permeable and -impermeable arterial segments was less in dexamethasone-treated mice than that for similar vessels in control mice (p less than 0.005, p less than 0.05, and p less than 0.01, respectively). The total number of small vesicles and the number of larger HRP-filled vesicles in arterioles was the same in treated and control mice. Dexamethasone therefore decreased the normal permeability of cerebral blood vessels to HRP. This decrease was accompanied by a decrease in the number of HRP-containing small endothelial vesicles. These data suggest that dexamethasone influences cerebral edema by decreasing the permeability of the cerebral vasculature for macromolecules.

A novel brain trauma model in the mouse: effects of dexamethasone treatment

“…Our findings -in accordance with those of others [7,22,27] -indicate that Dxm may counteract both the early and the delayed phases of the formation of vasogenic oedema in the brain, and may directly rescue nerve cells from excitotoxic cell death following its interaction with neuronal and glial GRs [1]. Previous studies have demonstrated that Dxm may significantly decrease the permeability of cerebral blood vessels to the macromolecule horseradish peroxidase in the mouse [7], and may thereby reduce cerebral oedema after brain injury. Such an action of Dxm on the BBB is also suggested following cold lesion.…”

Blood-Brain Barrier Damage Induces Release of α2-Macroglobulin

“…Recent findings suggest that glucocorticoids may stimulate ␣ 2 M release and inhibit up-regulation of MMP-9 (18,19). This is consistent with the concept that glucocorticoids may act as repair agents following BBB failure and edema formation (20). ␣ 2 M is a tetramer of four identical 180-kDa subunits exhibiting a ␤-cysteinyl-glutamyl-thiol ester bond and inhibits the target protease by physical entrapment.…”

Corticosteroids in brain cancer patients: benefits and pitfalls

“…It has been suggested that corticosteroids produce their anti-edema effect by reducing the permeability of tumor capillaries (Figure 2) [26,31,32]. As indicated previously, corticosteroids diffuse through the plasma membrane and bind to the cytoplasmic receptor, allowing the steroid–receptor complex to move to the nucleus where it directly affects transcription of genes and also interacts with other transcription factors, mediating nontranscriptional regulation of other signaling cascades (Figure 1) [19].…”