Critical Cerebral Perfusion Pressure at High Intracranial Pressure Measured by Induced Cerebrovascular and Intracranial Pressure Reactivity

Bragin, Denis E; Statom, Gloria; Yonas, Howard; Dai, Xing-Ping; Nemoto, Edwin M.

doi:10.1097/ccm.0000000000000655

Cited by 16 publications

(13 citation statements)

References 45 publications

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“…These measurements of perfusate flow confirm adequate and physiological perfusion of the brain regions examined and indicate that with a saline‐based perfusion fluid less viscous than blood, adequate perfusion can be maintained at pressures (40–70 mm Hg) close to the critical cerebral perfusion pressure of 50 mm Hg measured in the rat by Bragin et al . ().…”

Section: Discussionmentioning

confidence: 97%

Uptake and metabolism of sulphated steroids by the blood–brain barrier in the adult male rat

Qaiser

Dolman

Begley

et al. 2017

Journal of Neurochemistry

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Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found 3 H-PregS to enter more rapidly than 3 H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes. Although permeability measurements suggested a net efflux, addition of the efflux inhibitors GF120918 and/or MK571 to the perfusate reduced rather than enhanced the uptake of 3 H-DHEAS and 3 H-PregS; a further reduction was seen upon the addition of unlabelled steroid sulphate, suggesting a saturable uptake transporter.Analysis of brain fractions after 0.5 min perfusion with the 3 Hsteroid sulphates showed no further metabolism of PregS beyond the liberation of free steroid pregnenolone. By contrast, DHEAS underwent 17-hydroxylation to form androstenediol in both the steroid sulphate and the free steroid fractions, with some additional formation of androstenedione in the latter. Our results indicate a gain of free steroid from circulating steroid sulphates as hormone precursors at the blood-brain barrier, with implications for ageing, neurogenesis, neuronal survival, learning and memory.

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Section: Discussionmentioning

confidence: 97%

Uptake and metabolism of sulphated steroids by the blood–brain barrier in the adult male rat

Qaiser

Dolman

Begley

et al. 2017

Journal of Neurochemistry

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“…We subsequently showed that the critical CPP of the cerebral circulation obtained by increasing ICP was accurately identified as 50 mmHg by dopamine-induced ICP reactivity (iPRx) and cerebrovascular reactivity (iCVRx) (6). The apparent lower critical CPP at high ICP was attributable to a transition from normal capillary to microvascular shunt (MVS) flow as previously hypothesized (14).…”

Section: Introductionmentioning

confidence: 99%

High Intracranial Pressure Induced Injury in the Healthy Rat Brain

Dai

Bragina

Zhang

et al. 2016

Critical Care Medicine

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Objective We recently showed that increased intracranial pressure (ICP) to 50 mmHg in the healthy rat brain results in microvascular shunt (MVS) flow characterized by tissue hypoxia, edema and increased blood brain barrier permeability. We now determined whether increased ICP results in neuronal injury by Fluoro-Jade stain (FJS) and whether changes in cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) suggest nonnutritive MVS flow. Design Intracranial pressure was elevated by a reservoir of artificial cerebrospinal fluid (CSF) connected to the cisterna magna. Arterial blood gases, cerebral arterial-venous oxygen content difference (CAVDO2) and cerebral blood flow (CBF) by magnetic resonance imaging (MRI) were measured. FJS neurons were counted in histological sections of the right and left dorsal and lateral corticies and hippocampus. Setting University laboratory Subjects Male Sprague Dawley rats. Interventions Arterial pressure support if needed by i.v. dopamine infusion and base deficit corrected by sodium bicarbonate. Measurements and Main Results FJS neurons increased 2.5 and 5.5 fold at ICP of 30 and 50 mmHg; CPP of 57 ± 4 (mean ± SEM) and 47 ± 6 mmHg, respectively, (P<0.001); highest in the right and left cortices. Voxel frequency histograms of CBF showed a pattern consistent with MVS flow by dispersion to higher CBF at high ICP and decreased CMRO2. Conclusions High ICP likely caused neuronal injury due to a transition from normal capillary flow to nonnutritive MVS flow resulting in tissue hypoxia, edema and manifest by a reduction in CMRO2.

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“…[8][9][10][11] Recent studies indicate that the CBF response to a sustained decrease in CPP caused by a decrease in arterial blood pressure (ABP) or an increase in ICP has key physiological differences. [12][13][14] For example, Bragin et al 12,13 measured the cerebral haemodynamic response to sustained decrements of CPP (30 minutes at each level of ICP) and found when the decrease in CPP was brought about by an increased ICP, the lower limit of autoregulation was around 30 mm Hg, whereas with decreases in CPP brought about by a decreased ABP, the lower limit of autoregulation was around 50 mm Hg.…”

Section: Introductionmentioning

confidence: 99%

Cerebral haemodynamics during experimental intracranial hypertension

Donnelly

Czosnyka

Harland

et al. 2016

J Cereb Blood Flow Metab

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Intracranial hypertension is a common final pathway in many acute neurological conditions. However, the cerebral haemodynamic response to acute intracranial hypertension is poorly understood. We assessed cerebral haemodynamics (arterial blood pressure, intracranial pressure, laser Doppler flowmetry, basilar artery Doppler flow velocity, and vascular wall tension) in 27 basilar artery-dependent rabbits during experimental (artificial CSF infusion) intracranial hypertension. From baseline ($9 mmHg; SE 1.5) to moderate intracranial pressure ($41 mmHg; SE 2.2), mean flow velocity remained unchanged (47 to 45 cm/s; p ¼ 0.38), arterial blood pressure increased (88.8 to 94.2 mmHg; p < 0.01), whereas laser Doppler flowmetry and wall tension decreased (laser Doppler flowmetry 100 to 39.1% p < 0.001; wall tension 19.3 to 9.8 mmHg, p < 0.001). From moderate to high intracranial pressure ($75 mmHg; SE 3.7), both mean flow velocity and laser Doppler flowmetry decreased (45 to 31.3 cm/s p < 0.001, laser Doppler flowmetry 39.1 to 13.3%, p < 0.001), arterial blood pressure increased still further (94.2 to 114.5 mmHg; p < 0.001), while wall tension was unchanged (9.7 to 9.6 mmHg; p ¼ 0.35).This animal model of acute intracranial hypertension demonstrated two intracranial pressuredependent cerebroprotective mechanisms: with moderate increases in intracranial pressure, wall tension decreased, and arterial blood pressure increased, while with severe increases in intracranial pressure, an arterial blood pressure increase predominated. Clinical monitoring of such phenomena could help individualise the management of neurocritical patients.

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Critical Cerebral Perfusion Pressure at High Intracranial Pressure Measured by Induced Cerebrovascular and Intracranial Pressure Reactivity

Abstract: Critical cerebral perfusion pressure of 50 mm Hg was accurately determined by induced intracranial pressure reactivity and induced cerebrovascular reactivity, whereas the static method failed.

Cited by 16 publications

References 45 publications

Uptake and metabolism of sulphated steroids by the blood–brain barrier in the adult male rat

Uptake and metabolism of sulphated steroids by the blood–brain barrier in the adult male rat

High Intracranial Pressure Induced Injury in the Healthy Rat Brain

Cerebral haemodynamics during experimental intracranial hypertension

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