Effect of hypothermia on blood-brain barrier permeability following traumatic brain injury in chronically ethanol-treated rats.

The objective of this study was to investigate the effect of hypothermia on the blood-brain barrier (BBB) disruption caused by traumatic brain injury (TBI) in chronically ethanol-treated rats. BBB permeability was measured using Evans blue (EB) dye. Arterial blood pressure levels of animals in hypothermic groups decreased significantly. The EB dye extravasation into the brain significantly increased in hypothermia and at 6 and 24 h after TBI. In ethanol-treated rats that were subjected to TBI, hypothermia led to a significant decrease in EB dye content in the brain at 24 h but not at 6 h after TBI when compared with TBI alone.

Effects of lipopolysaccharide on the blood-brain barrier permeability in prolonged nitric oxide blockade-induced hypertensive rats.

The authors investigated the effects of lipopolysaccharide (LPS) on the blood-brain barrier (BBB) integrity and the activity of astrocytes during the Nw-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II in rats. They measured the changes in the BBB permeability using the Evans blue (EB) dye and concomitantly in the levels of TNF-a, IL-1b, and IL-6 in serum and nitric oxide in plasma. The authors performed two tight junction-specific proteins, zonula occludens-1 and occludin, and glial fibrillary acidic protein, by using immunohisto-chemical method. The serum levels of TNF-a, IL-1 IL-6, and the plasma level of nitric oxide significantly increased in LPS-treated rats (p<.01). The EB dye extravasation increased in cerebellum (p<.001) and diencephalon (p<.05) of L-NAME plus ANG II-treated animals. However, LPS reduced the increased EB dye extravasation in the brain regions of L-NAME-induced hypertensive rats treated with ANG II (p<.001). In L-NAME, there was a considerable loss of staining in both zonula occludens-1 and occludin. Staining for zonula occludens-1 and occludin was highly intensive in animals treated with LPS. Glial fibrillary acidic protein staining was seen in a few astrocytes in brains of L-NAME-treated animals. However, this staining showed an increased intensity in the brain sections of animals treated with LPS. This study indicates that, in L-NAME hypertensive rats, ANG II leads to an increase in the extravasation of EB dye to brain as a result of decreased activity of tight junction proteins and astrocytes, and LPS could significantly attenuate the EB dye transport to the brain through the increased activity of tight junction proteins and astrocytes.

Effect of losartan on the blood-brain barrier permeability in diabetic hypertensive rats.

Our previous publication has stressed the benefits of losartan, an angiotensin II receptor blocker, on the permeability of blood-brain barrier (BBB) and blood pressure during L-NAME-induced hypertension. This study reports the impacts of anti-hypertensive treatment by losartan on the brain endothelial barrier function and the arterial blood pressure, during acute hypertension episode, in experimentally diabetic hypertensive rats. Systolic blood pressure measurements were taken with tail cuff method before and during administration of L-NAME (0.5 mg/ml). We induced diabetes by using alloxan (50 mg/kg, i.p). Losartan (3 mg/kg, i.v) was given to rats following the L-NAME treatment. Acute hypertensive vascular injury was induced by epinephrine (40 microg/kg). The BBB disruption was quantified according to the extravasation of the Evans blue (EB) dye. L-NAME induced a significant increase in arterial blood pressure on day 14 in normoglycemic and hyperglycemic rats (p < 0.05). Losartan significantly reduced the increased blood pressure in hypertensive and diabetic hypertensive rats (p < 0.01). Epinephrine-induced acute hypertension in diabetic hypertensive rats increased the content of EB dye dramatically in cerebellum and diencephalon (p < 0.01) and slightly in both cerebral cortex (p < 0.05). Losartan treatment reduced the increased BBB permeability to EB dye in the brain regions of diabetic hypertensive rats treated with epinephrine (p < 0.05). This study indicates that, in diabetic hypertensive rats, epinephrine administration leads to an increase in microvascular-EB-albumin efflux to brain, however losartan treatment significantly attenuates this protein's transport to brain tissue.

Effect of aluminum on the blood-brain barrier permeability during nitric oxide-blockade-induced chronic hypertension in rats.

We examined the effect of aluminum on the permeability of the blood-brain barrier (BBB) during nitric oxide-blockade-induced chronic hypertension in rats. Animals were given the inhibitor of nitric oxide synthase, L-NAME (Nomega-nitro-L-arginine methyl ester), for 4 wk to induce chronic hypertension. Two groups of rats were given an intraperitoneal injection of aluminum chloride. The integrity of the BBB was assessed by a quantitative measurement for Evans blue (EB) dye. The arterial blood pressure in L-NAME- and L-NAME plus aluminum-treated animals was significantly elevated from 115+/-2.8 and 110+/-1.7 mm Hg to 174+/-5.2 and 175+/-4.8 mm Hg, respectively (p < 0.01). The EB dye content in the brain regions of the rats in the L-NAME group was increased, but there was no statistical significance compared to the saline group. The extravasation of EB dye was significantly increased in the brain regions of the animals treated with aluminum compared to the rats treated with saline (p < 0.05). A significantly higher EB dye content in the brain regions was observed in the L-NAME plus aluminum group compared to L-NAME, aluminum, and saline groups (p < 0.01). These findings indicate that exposure to a high level of aluminum leads to an additional increase in BBB permeability where nitric oxide-blockade-induced chronic hypertension potentiates the effect of aluminum to enhance BBB permeability to EB dye.

Magnesium sulfate attenuates increased blood-brain barrier permeability during insulin-induced hypoglycemia in rats.

Magnesium probably protects brain tissue against the effects of cerebral ischemia, brain injury and stroke through its actions as a calcium antagonist and inhibitor of excitatory amino acids. The effects of magnesium sulfate on cerebrovascular permeability to a dye, Evans blue, were studied during insulin-induced hypoglycemia with hypothermia in rats. Hypoglycemia was induced by an intramuscular injection of insulin. After giving insulin, each animal received MgSO4 (270 mg/kg) ip, followed by a 27 mg/kg dose every 20 min for 2.5 h. Plasma glucose and Mg2+ levels of animals were measured. Magnesium concentrations increased in the serum following MgSO4 administration (6.05+/-0.57 vs. 2.58+/-0.14 mg/dL in the Mg2+ group, and 7.14+/-0.42 vs. 2.78+/-0.06 mg/dL in the insulin + Mg2+ group, P < 0.01). Plasma glucose levels decreased following hypoglycemia (4+/-0.66 vs. 118+/-2.23 mg/dL in the insulin group, and 7+/-1.59 vs. 118+/-4.84 mg/dL in the insulin + Mg2+ group, P < 0.01). Blood-brain barrier permeability to Evans blue considerably increased in hypoglycemic rats (P < 0.01). In contrast, blood-brain barrier permeability to Evans blue was significantly reduced in treatment of hypoglycemic rats with MgSO4 (P < 0.01). These results indicate that Mg2+ greatly reduced the passage of exogenous vascular tracer bound to albumin into the brain during hypoglycemia with hypothermia. Mg2+ could have protective effects on blood-brain barrier permeability against insulin-induced hypoglycemia.

Effect of aluminum on the blood-brain barrier permeability in acute and chronically hyperglycemic rats.

This study examined the changes in blood-brain barrier (BBB) permeability following acute aluminum (Al) exposure during acute and chronic hyperglycemia in rats. Acute hyperglycemia was induced by intraperitoneal injection of glucose solution at 30 min after giving Al. Chronic hyperglycemia was made by an injection of alloxan monohydrate. BBB permeability was measured in the four regions of the brain at 1 h after administrating Al by spectrophotometric quantification of Evans blue (EB) dye. The extravasation of EB dye was significantly more extensive in the two regions of brain in the groups treated with Al, Al plus glucose, and alloxan plus Al than in the groups treated with saline, glucose, and alloxan alone (p < 0.05). Under acute and chronic hyperglycemia plus Al treatment, the BBB permeability to EB was significantly higher than that observed solely in Al-treated rats (p < 0.05). These data indicate that Al toxicity leads to an additional increase in BBB permeability, in which acute and chronic hyperglycemia potentiates the effects of Al to enhance BBB permeability to EB.

Effects of profound hypothermia on the blood-brain barrier permeability in acute and chronically ethanol treated rats.

This study examines the effects of profound hypothermia on the blood-brain barrier (BBB) permeability in ethanol administrated rats. Vascular permeability to intravenously injected Evans blue (EB) was quantitatively examined in the brain regions of rats. Rats were treated with ethanol acute and chronically. Rectal temperature of rats was dropped into 20+/-1 degrees C during profound hypothermia. Mean arterial blood pressure in both acute and chronic ethanol treatments plus hypothermia significantly dropped into low levels as well as in hypothermia alone (P<0.01). Hypothermia led to a significant increase in the content of EB dye in the brain regions of rats (P<0.05). Both acute and chronic ethanol treatments plus hypothermia did not lead to a significant increase in the BBB permeability against intravenously injected EB dye. We conclude that ethanol intake protects the BBB against the effects of hypothermia.