No evidence for cerebral hypoperfusion during cerebral malaria

Clavier, N.; Rahimy, Chaerif; Falanga, Pierre B.; Ayivi, B.; Payen, Didier

doi:10.1097/00003246-199903000-00047

Cited by 34 publications

(20 citation statements)

References 22 publications

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“…Cerebral hemodynamics is particularly difficult to compare because of few and apparently conflicting findings in human studies. Transcranial Doppler sonography studies showed mostly normal and sometimes increased CBF velocities in CM patients, [12][13][14][15] although wide ranges and large differences between brain hemispheres were observed. In the larger study, although 30% of children initially presented increased CBF velocities, the children with fatal outcomes presented low CBF velocity recordings after admission.…”

Section: Discussionmentioning

confidence: 93%

“…7,10 Ischemic damage has also been shown in children with CM and was associated with severe neurological sequelae. 11 On the other hand, transcranial Doppler sonography studies showed normal or even increased cerebral blood flow (CBF) velocities [12][13][14][15] in large arteries during CM, which associated with microcirculatory obstruction has been suggested to increase cerebral blood volume leading to intracranial hypertension. 16 Alternatively, collateral flow has been proposed as a mechanism to reconcile the findings of normal or increased CBF velocities and impaired perfusion, 17 an interpretation supported by findings of hyperdynamic flow in capillaries adjacent to obstructed vessels.…”

mentioning

confidence: 99%

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Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine

Cabrales

Zaniní

Meays

et al. 2010

The American Journal of Pathology

146

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Brain hemodynamics in cerebral malaria (CM) is poorly understood , with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. Using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of CM by Plasmodium berghei ANKA , we show that murine CM is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood velocity. Leukocyte sequestration further decreased perfusion by narrowing luminal diameters in the affected vessels and blocking capillaries. Remarkably , vascular collapse at various degrees was observed in 44% of mice with CM , which also presented more severe vasoconstriction. Coadministration of artemether and nimodipine , a calcium channel blocker used to treat postsubarachnoid hemorrhage vasospasm, to mice presenting CM markedly increased survival compared with artemether plus vehicle only. Administration of nimodipine induced vasodilation and increased pial blood flow. We conclude that vasoconstriction and vascular collapse play a role in murine CM pathogenesis and nimodipine holds potential as adjunctive therapy for CM.

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine

Cabrales

Zaniní

Meays

et al. 2010

The American Journal of Pathology

146

View full text Add to dashboard Cite

show abstract

“…This may be another reason why relatively crude measurements of perfusion have yielded conflicting results about blood flow in human CM. Transcranial Doppler ultrasound failed to demonstrate decreased blood flow in human CM 56 ; however, the resolution of the technique may not be sufficient to detect localized foci of hypoperfusion and occlusion. Low resolution has also proved limiting in magnetic resonance imaging in patients with CM.…”

Section: Hypoxia and Cerebralmentioning

confidence: 88%

CNS Hypoxia Is More Pronounced in Murine Cerebral than Noncerebral Malaria and Is Reversed by Erythropoietin

Hempel

Combes

Hunt

et al. 2011

The American Journal of Pathology

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Cerebral malaria (CM) is associated with high mortality and risk of sequelae, and development of adjunct therapies is hampered by limited knowledge of its pathogenesis. To assess the role of cerebral hypoxia, we used two experimental models of CM, Plasmodium berghei ANKA in CBA and C57BL/6 mice, and two models of malaria without neurologic signs, P. berghei K173 in CBA mice and P. berghei ANKA in BALB/c mice. Hypoxia was demonstrated in brain sections using intravenous pimonidazole and staining with hypoxia-inducible factor-1␣-specific antibody. Cytopathic hypoxia was studied using poly (ADP-ribose) polymerase-1 (PARP-1) gene knockout mice. The effect of erythropoietin, an oxygen-sensitive cytokine that mediates protection against CM, on cerebral hypoxia was studied in C57BL/6 mice. Numerous hypoxic foci of neurons and glial cells were observed in mice with CM. Substantially fewer and smaller foci were observed in mice without CM, and hypoxia seemed to be confined to neuronal cell somas. PARP-1-deficient mice were not protected against CM, which argues against a role for cytopathic hypoxia. Erythropoietin therapy reversed the development of CM and substantially reduced the degree of neural hypoxia. These findings demonstrate cerebral hypoxia in malaria, strongly associated with cerebral dysfunction and a possible target for adjunctive therapy.

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“…The nature of hemodynamics disturbances in human CM is unclear, with conflicting results showing either vasodilatation or stenosis of brain arteries (Newton et al, 1997;Clavier et al, 1999). Vessel vasodilatation was thought to cause brain swelling (Looareesuwan et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Imaging Experimental Cerebral MalariaIn Vivo: Significant Role of Ischemic Brain Edema

Penet¹,

Viola²,

et al. 2005

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The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.

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No evidence for cerebral hypoperfusion during cerebral malaria

Abstract: Because jugular bulb venous oxygen saturation remained within the normal range, cerebral hyperemia seems to be an adaptive response to altered systemic determinants, which argues against a hemodynamic mechanism for altered consciousness during cerebral malaria.

Cited by 34 publications

References 22 publications

Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine

Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine

CNS Hypoxia Is More Pronounced in Murine Cerebral than Noncerebral Malaria and Is Reversed by Erythropoietin

Imaging Experimental Cerebral MalariaIn Vivo: Significant Role of Ischemic Brain Edema

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