Induction of pinocytosis in cerebral vessels by acute hypertension and by hyperosmolar solutions

Hansson, Hans‐Arne; Johansson, Barbro

doi:10.1002/jnr.490050303

Cited by 54 publications

(20 citation statements)

References 16 publications

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“…The properties of the BBB suggest that a highly selective exchange system has evolved between the blood and brain to provide a homeostatic environment for the brain in the normal physiological state (41). This controlled environment may be altered by an increase in permeability under physiological conditions like hypertension (1,24,35,36) or by physical damage of the endothelial membranes occurring with pathological conditions such as trauma, ischemia, tumors, and allergic or inflammatory diseases (3,30). The inflammation and swelling of brain vasculature and tissue during infection with viruses such as HSV-1 suggest that viral infection of the CNS may also alter the permeability of the BBB (39,45).…”

mentioning

confidence: 99%

Intravenous Infusion of Cereport Increases Uptake and Efficacy of Acyclovir in Herpes Simplex Virus-Infected Rat Brains

Bidanset

Placidi

Rybak

et al. 2001

Antimicrob Agents Chemother

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The outcome of herpes simplex virus (HSV) infections manifesting as encephalitis in healthy or immunocompromised individuals is generally very poor with mortality rates of about 8 to 28% with treatment. The long-term prognosis of survivors is often problematic, posing the need for alternative treatments that may decrease the mortality and morbidity associated with herpes encephalitis. This study addresses one such approach that includes a temporary permeabilization of the blood-brain barrier during treatment with acyclovir (ACV). In these studies we utilized a synthetic bradykinin analog, Cereport (RMP-7), in conjunction with ACV to treat HSV infection of the brain in a rat model. Cereport, infused intravenously via the jugular vein, was shown to increase [ 14 C]ACV uptake in both the HSV-1-infected and -uninfected rat brain by approximately two-to threefold, correlating with enhanced efficacy of ACV in various brain compartments. In another series of experiments to determine efficacy, various doses of unlabeled ACV were administered during infusion with RMP-7. The decrease in viral titers in the temporal regions of the brain after 5 days of treatment suggested that this approach enhanced the efficacy of ACV treatment. These data indicated that Cereport infused with ACV enhances both the penetration and efficacy of this drug in the treatment of an experimental HSV-1 infection of the rat brain.Herpes simplex virus (HSV) infections in humans can manifest as a life-threatening disease with high mortality and significant morbidity in survivors. These infections can be caused by either HSV-1 or HSV-2 (2, 46). In neonates, primary infection that occurs during or shortly after birth is usually symptomatic within 1 month and is frequently lethal (42,43,46). Although treatment with either vidarabine or acyclovir (ACV) significantly reduces the mortality rate, up to 15% of those with encephalitis still do not survive (28,42,43,45). In older individuals, encephalitis caused by primary or recurrent HSV infection results in a 70% mortality rate without treatment and an 8 to 28% mortality rate with treatment depending on when treatment is initiated (32,45,46). This disease is characterized by acute necrotizing focal encephalopathy, inflammation and swelling of the brain tissue, and petechiae or larger hemorrhages in the brain (9,26,39,47). Although therapy with either vidarabine or ACV (42, 44) has proven to be effective in reducing mortality rates of HSV encephalitis, the long-term prognosis of the survivors is less than optimal. A few survivors suffer relapses, but many others have learning and memory abnormalities and impairment of general orientation and perceptive-motor skills (12,14,29). This current state of HSV encephalitis-associated mortality and morbidity suggests that alternative approaches to treatment need to be developed.One possible reason for reduced efficacy in the central nervous system (CNS) may be failure of the drug to penetrate the blood-brain barrier (BBB) and enter the CNS tissues. Inefficient penetra...

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mentioning

confidence: 99%

Intravenous Infusion of Cereport Increases Uptake and Efficacy of Acyclovir in Herpes Simplex Virus-Infected Rat Brains

Bidanset

Placidi

Rybak

et al. 2001

Antimicrob Agents Chemother

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“…In the present study, BBB permeability was measured using LY, a polar compound that does not pass through the high electrical resistance tight junctions of the BBB [21] and is a marker of transcellular transport [9,19]. We used cerebral pial arteries that have BBB properties [1,26] to investigate changes in permeability in response to ovariectomy and estrogen replacement in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…We used cerebral pial arteries that have BBB properties [1,26] to investigate changes in permeability in response to ovariectomy and estrogen replacement in vitro. In cerebral endothelium that comprised the BBB, transcellular transport is low under normal conditions, but increases substantially under pathologic conditions in which barrier permeability is enhanced leading to vasogenic edema [19,34,50]. One of the earliest microscopic findings in an experimental animal model of acute hypertension (i.e., hypertensive encephalopathy) is an increased rate of pinocytosis in the cerebrovascular endothelium of arteries and arterioles, which allows significant passage of fluid and molecules into the brain [19,34].…”

Section: Discussionmentioning

confidence: 99%

“…In cerebral endothelium that comprised the BBB, transcellular transport is low under normal conditions, but increases substantially under pathologic conditions in which barrier permeability is enhanced leading to vasogenic edema [19,34,50]. One of the earliest microscopic findings in an experimental animal model of acute hypertension (i.e., hypertensive encephalopathy) is an increased rate of pinocytosis in the cerebrovascular endothelium of arteries and arterioles, which allows significant passage of fluid and molecules into the brain [19,34]. Our own studies have shown in cerebral pial arteries that pressure alone is a potent stimulus for pinocytosis and transcellular transport [9].…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-Brain Barrier Permeability

Cipolla¹,

Godfrey²,

Wiegman³

2009

UMIC

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Objective-We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability.Methods-Female ovariectomized Sprague Dawley rats were replaced with estradiol (E 2 ) and estriol (E 3 ) (OVX+E; N=13) and compared to ovariectomized animals without replacement (OVX; N=14) and intact controls (CTL, proestrous; N=13). Passive and active diameters, percent tone and passive distensibility of pressurized PA were compared. In addition, BBB permeability to Lucifer Yellow, a marker of transcellular transport, was compared in cerebral arteries.Results-Ovariectomy increased myogenic tone in PA compared to CTL that was not ameliorated by estrogen treatment. Percent tone at 75 mmHg for CTL vs. OVX and OVX+E was 44 ± 3% vs. 51 ± 1% and 54 ± 3% (p<0.01 vs. CTL for both). No differences were found in passive diameters or distensibility between the groups. BBB permeability increased 500% in OVX vs. CTL animals, however, estrogen replacement restored barrier properties: flux of Lucifer Yellow for CTL, OVX and OVX+E was (ng/mL): 3.4 ± 1.2, 20.2 ± 5.3 (p<0.01 vs. CTL) and 6.15 ± 1.2 (n.s.).Conclusions-These results suggest that estrogen replacement may not be beneficial for small vessel disease in the brain, but may limit BBB disruption and edema under conditions that cause it.

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“…Studies of osmotic opening of the BBB by hypertonic solutions, such as mannitol and urea infused via the carotid artery, provided controversial results, with studies for and against this mechanism of tracer passage, with many more studies demonstrating passage of tracer through endothelium by enhanced endothelial caveolae (Hansson and Johansson, 1980;Houthoff et al, 1982;Farrell and Shivers, 1984;Nagy et al, 1984). However, use of molecular markers smaller than HRP, such as ionic lanthanum (MW 138.9 Da) and […”

Section: Tight Junctionsmentioning

confidence: 96%

Structure and Pathology of the Blood–Brain Barrier

Nag¹

2007

Handbook of Neurochemistry and Molecular Neurobiology

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Induction of pinocytosis in cerebral vessels by acute hypertension and by hyperosmolar solutions

Cited by 54 publications

References 16 publications

Intravenous Infusion of Cereport Increases Uptake and Efficacy of Acyclovir in Herpes Simplex Virus-Infected Rat Brains

Intravenous Infusion of Cereport Increases Uptake and Efficacy of Acyclovir in Herpes Simplex Virus-Infected Rat Brains

The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-Brain Barrier Permeability

Structure and Pathology of the Blood–Brain Barrier

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