The effects of hypoxia on the ERG in paediatric cerebral malaria

Lochhead, Jonathan; Movaffaghy, Armand; Falsini, Benedetto; Harding, Simon; Riva, Charles E.; Molyneux, Malcolm E.

doi:10.1038/eye.2009.162

Cited by 13 publications

(9 citation statements)

References 17 publications

(25 reference statements)

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“…Noteworthy, the current work complements these findings showing that CM evokes functional changes in the retinal physiology which was evidenced by low photopic response (reducing a- and b-wave amplitude) observed in mice at 7 days post P. berghei infection. These results are in agreement with early observations which describe ophthalmologic dysfunctions in children with CM induced by P. falciparum infection [ 46 , 47 ]. The tissue events responsible for the retinal electrophysiological impairment induced by CM are still not fully understood.…”

Section: Discussionsupporting

confidence: 93%

Cerebral malaria induces electrophysiological and neurochemical impairment in mice retinal tissue: possible effect on glutathione and glutamatergic system

Oliveira

Kauffmann

Leão

et al. 2017

Malar J

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BackgroundCerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has usually been associated with cognitive, behavioural and motor dysfunctions, being the retinopathy the most serious consequence resulting from the disease. The pathophysiological mechanisms underlying this complication remain incompletely understood. Several experimental models of CM have already been developed in order to clarify those mechanisms related to this syndrome. In this context, the present work has been performed to investigate which possible electrophysiological and neurochemistry alterations could be involved in the CM pathology.MethodsExperimental CM was induced in Plasmodium berghei-infected male and female C57Bl/6 mice. The survival and neurological symptoms of CM were registered. Brains and retina were assayed for TNF levels and NOS2 expression. Electroretinography measurements were recorded to assessed a- and b-wave amplitudes and neurochemicals changes were evaluated by determination of glutamate and glutathione levels by HPLC.ResultsSusceptible C57Bl/6 mice infected with ≈ 106 parasitized red blood cells (P. berghei ANKA strain), showed a low parasitaemia, with evident clinical signs as: respiratory failure, ataxia, hemiplegia, and coma followed by animal death. In parallel to the clinical characterization of CM, the retinal electrophysiological analysis showed an intense decrease of a- and-b-wave amplitude associated to cone photoreceptor response only at the 7 days post-infection. Neurochemical results demonstrated that the disease led to a decrease in the glutathione levels with 2 days post inoculation. It was also demonstrated that the increase in the glutathione levels during the infection was followed by the increase in the 3H-glutamate uptake rate (4 and 7 days post-infection), suggesting that CM condition causes an up-regulation of the transporters systems. Furthermore, these findings also highlighted that the electrophysiological and neurochemical alterations occurs in a manner independent on the establishment of an inflammatory response, once tumour necrosis factor levels and inducible nitric oxide synthase expression were altered only in the cerebral tissue but not in the retina.ConclusionsIn summary, these findings indicate for the first time that CM induces neurochemical and electrophysiological impairment in the mice retinal tissue, in a TNF-independent manner.

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Section: Discussionsupporting

confidence: 93%

Cerebral malaria induces electrophysiological and neurochemical impairment in mice retinal tissue: possible effect on glutathione and glutamatergic system

Oliveira

Kauffmann

Leão

et al. 2017

Malar J

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“…This increase is probably an adaptive response to high a metabolic demand to match oxygen and nutrient delivery to requirements since jugular bulb venous oxygen saturation remains within normal(50). Recent studies of the retina have however provided evidence for decreased local perfusion(51, 52). In the eye, multiple discrete areas (100-1000μm) of retinal whitening are observed in most children with cerebral malaria.…”

Section: Mechanisms Of Brain Injury In Cerebral Malariamentioning

confidence: 99%

“…These areas have impaired capillary perfusion on fluorescein angiography(51), figure 2. Physiologically, reduced local perfusion is associated with an abnormal electroretinograph(52). If the retina mirrors events in the brain, similar obstruction may be present in the brain and coma in cerebral malaria may partly be a result of under-perfusion in multiple but small areas of the brain.…”

Section: Mechanisms Of Brain Injury In Cerebral Malariamentioning

confidence: 99%

Cerebral Malaria: Mechanisms of Brain Injury and Strategies for Improved Neurocognitive Outcome

et al. 2010

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Cerebral malaria is the most severe neurological complication of infection with Plasmodium falciparum. With over 575,000 cases annually, children in sub-Saharan Africa are the most affected. Surviving patients have an increased risk of neurological and cognitive deficits, behavioral difficulties and epilepsy making cerebral malaria a leading cause of childhood neuro-disability in the region. The pathogenesis of neuro-cognitive sequelae is poorly understood: coma develops through multiple mechanisms and there may be several mechanisms of brain injury. It is unclear how an intravascular parasite causes such brain injury. Understanding these mechanisms is important to develop appropriate neuro-protective interventions. This paper examines possible mechanisms of brain injury in cerebral malaria, relating this to the pathogenesis of the disease and explores prospects for improved neuro-cognitive outcome.

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“…Whitening in retinal vein occlusion is associated with swelling of the inner nuclear and outer plexiform layers of the retina (Sarda et al , 2011). In paediatric cerebral malaria there is a significant inverse correlation between electroretinographic cone b-wave amplitude and severity of retinal whitening (Lochhead et al , 2010), indicating dysfunction of bipolar cells in the inner nuclear layer. The inner nuclear and outer plexiform layers are supplied by the deep capillary plexus, which forms the superficial half of a watershed with the underlying choriocapillaris (McLeod, 2010).…”

Section: Manifestations Of Cerebral Malaria In the Paediatric Retinamentioning

confidence: 99%

Cerebral malaria in children: using the retina to study the brain

MacCormick

Beare

Taylor

et al. 2014

Brain

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Cerebral malaria is a dangerous complication of Plasmodium falciparum infection, which takes a devastating toll on children in sub-Saharan Africa. Although autopsy studies have improved understanding of cerebral malaria pathology in fatal cases, information about in vivo neurovascular pathogenesis is scarce because brain tissue is inaccessible in life. Surrogate markers may provide insight into pathogenesis and thereby facilitate clinical studies with the ultimate aim of improving the treatment and prognosis of cerebral malaria. The retina is an attractive source of potential surrogate markers for paediatric cerebral malaria because, in this condition, the retina seems to sustain microvascular damage similar to that of the brain. In paediatric cerebral malaria a combination of retinal signs correlates, in fatal cases, with the severity of brain pathology, and has diagnostic and prognostic significance. Unlike the brain, the retina is accessible to high-resolution, non-invasive imaging. We aimed to determine the extent to which paediatric malarial retinopathy reflects cerebrovascular damage by reviewing the literature to compare retinal and cerebral manifestations of retinopathy-positive paediatric cerebral malaria. We then compared retina and brain in terms of anatomical and physiological features that could help to account for similarities and differences in vascular pathology. These comparisons address the question of whether it is biologically plausible to draw conclusions about unseen cerebral vascular pathogenesis from the visible retinal vasculature in retinopathy-positive paediatric cerebral malaria. Our work addresses an important cause of death and neurodisability in sub-Saharan Africa. We critically appraise evidence for associations between retina and brain neurovasculature in health and disease, and in the process we develop new hypotheses about why these vascular beds are susceptible to sequestration of parasitized erythrocytes.

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The effects of hypoxia on the ERG in paediatric cerebral malaria

Cited by 13 publications

References 17 publications

Cerebral malaria induces electrophysiological and neurochemical impairment in mice retinal tissue: possible effect on glutathione and glutamatergic system

Cerebral malaria induces electrophysiological and neurochemical impairment in mice retinal tissue: possible effect on glutathione and glutamatergic system

Cerebral Malaria: Mechanisms of Brain Injury and Strategies for Improved Neurocognitive Outcome

Cerebral malaria in children: using the retina to study the brain

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