Retinopathy-Positive Cerebral Malaria Is Associated With Greater Inflammation, Blood-Brain Barrier Breakdown, and Neuronal Damage Than Retinopathy-Negative Cerebral Malaria

Villaverde, Chandler; Namazzi, Ruth; Shabani, Estela; Park, Gregory S.; Datta, Dibyadyuti; Hanisch, Benjamin; Opoka, Robert O.; John, Chandy C.

doi:10.1093/jpids/piz082

Cited by 18 publications

(16 citation statements)

References 25 publications

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“…Observational cohort study 178 elevations of BBs in CSF of tuberculous meningitis patients (GFAP, S100 calcium-binding protein [S100B], and neuronspecific enolase [NSE]), [172][173][174][175] HIV patients (NfL, GFAP, and S100B), [176][177][178][179][180] and cerebral malaria (S100B, NSE, tau proteins, and inflammatory protein markers). [181][182][183][184][185][186] Protein biomarkers of CNS damage have also been detected after a variety of acute injury modalities. [193][194][195][196][197][198][199][200][201] Elevations of brain injury biomarkers, including GFAP and ubiquitin C-terminal hydrolase L1 (UCH-L1), have been detected in humans and animals acutely after diverse brain injuries, including TBI, 202,203 ischemic/hemorrhagic stroke, 198 cardiac arrest, 204 hypoxia, 196 seizures, 194 and even drug toxicity.…”

Section: Use Of Blood Biomarkersmentioning

confidence: 99%

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients

DeKosky

Kochanek

Valadka

et al. 2021

Journal of Neurotrauma

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19

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Section: Use Of Blood Biomarkersmentioning

confidence: 99%

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients

DeKosky

Kochanek

Valadka

et al. 2021

Journal of Neurotrauma

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“…In general, disruption of the blood–brain barrier, subsequent infiltration of immune cells, and hemorrhage are known to comprise a critical mechanism of CM that can cause nerve tissue damage [ 4 ]. Previous research has shown that neuronal damage can lead to neurological sequelae in children with CM and mice with experimental cerebral malaria (ECM) [ 5 – 7 ], but the underlying mechanism remains unclear. Recently, significantly increased levels of oxidative stress were detected in patients with severe malaria, including those with CM [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis participates in neuron damage in experimental cerebral malaria and is partially induced by activated CD8+ T cells

Shen

Wang

et al. 2022

Mol Brain

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Cerebral malaria is the most serious complication of malaria infection, with 26% of surviving children having neurological sequelae, which may be caused by neuron damage, but the mechanism is not clear. Ferroptosis has been reported to play an important role in neuron damage in several nervous system diseases. However, the occurrence of ferroptosis in experimental cerebral malaria (ECM) pathogenesis is still unknown. In this study, we firstly detected increased levels of malondialdehyde (MDA) and iron, which are indicators of ferroptosis, in the cerebrum of ECM mice. Some important regulators of ferroptosis, including upregulated expression of transferrin receptor 1 (TfR1) and acyl-CoA synthetase long-chain family member 4 (ACSL4), and downregulation of glutathione peroxidase 4 (GPX4) levels, were also confirmed in ECM mice. Consistently, neuron damage, which was detected in the cerebrum of ECM mice, was positively correlated with reduced GPX4 expression and furtherly rescued by administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1). In addition, primary neurons were damaged by activated CD8+ T cells, an effect that was also partially rescued by Fer-1 on amyloid precursor protein expression and mitochondrial membrane potential levels in vitro. Activated CD8+ T cells were also shown to infiltrate the cerebrum of ECM mice and upregulate TfR1 expression in primary neurons, which may be an important event for inducing ferroptosis in ECM. Altogether, we show that ferroptosis contributes to neuron damage in ECM pathogenesis, and activated CD8+ T cells may be important inducers of neuronal ferroptosis. Hence, targeting ferroptosis may be a promising adjuvant therapeutic strategy for neurological sequelae in patients with cerebral malaria.

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“…These proteins are crucial markers of inflammation, and have been investigated by previous studies in malaria patients. 10,[17][18][19] Also we compared changes in full blood count (FBC) indices in the children and how they associate with P. falciparum infection. The data from this study suggest that the HbAS genotype is associated with better control of P. falciparum malaria-induced inflammatory response than the HbAA genotype, with resultant milder APR during P. falciparum infection/malaria in children with the HbAS genotype compared to the HbAA genotype.…”

Section: Introductionmentioning

confidence: 99%

Acute Phase Responses Vary Between Children of HbAS and HbAA Genotypes During Plasmodium falciparum Infection

Tetteh¹,

Addai‐Mensah²,

Kyei-Baafour³

et al. 2021

JIR

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Purpose Haemoglobin genotype S is known to offer protection against Plasmodium falciparum infections but the mechanism underlying this protection is not completely understood. Associated changes in acute phase proteins (APPs) during Plasmodium falciparum infections between Haemoglobin AA (HbAA) and Haemoglobin AS (HbAS) individuals also remain unclear. This study aimed to evaluate changes in three APPs and full blood count (FBC) indices of HbAA and HbAS children during Plasmodium falciparum infection. Methods Venous blood was collected from three hundred and twenty children (6 months to 15 years) in Begoro in Fanteakwa District of Ghana during a cross-sectional study. Full blood count (FBC) indices were measured and levels of previously investigated APPs in malaria patients; C-reactive protein (CRP), ferritin and transferrin measured using Enzyme-Linked Immunosorbent Assays. Results Among the HbAA and HbAS children, levels of CRP and ferritin were higher in malaria positive children as compared to those who did not have malaria. The mean CRP levels were significantly higher among HbAA children (p=0.2e-08) as compared to the HbAS children (p=0.43). Levels of transferrin reduced in both HbAA and HbAS children with malaria, but the difference was only significant among HbAA children (p=0.0038), as compared to the HbAS children. No significant differences were observed in ferritin levels between HbAA and HbAS children in both malaria negative (p=0.76) and positive (p=0.26) children. Of the full blood count indices measured, red blood cell count (p=0.044) and haemoglobin (Hb) levels (p=0.017) differed between HbAA and HbAS in those without malaria, with higher RBC counts and lower Hb levels found in HbAS children. In contrast, during malaria, lymphocyte and platelet counts were elevated, whilst granulocytes and Mean Cell Haematocrit counts were reduced among children of the HbAS genotypes. Conclusion Significant changes in APPs were found in HbAA children during malaria as compared to HbAS children, possibly due to differences in malaria-induced inflammation levels. This suggests that the HbAS genotype is associated with better control of P. falciparum infection-induced inflammatory response than HbAA genotype.

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Retinopathy-Positive Cerebral Malaria Is Associated With Greater Inflammation, Blood-Brain Barrier Breakdown, and Neuronal Damage Than Retinopathy-Negative Cerebral Malaria

Cited by 18 publications

References 25 publications

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients

Ferroptosis participates in neuron damage in experimental cerebral malaria and is partially induced by activated CD8+ T cells

Acute Phase Responses Vary Between Children of HbAS and HbAA Genotypes During Plasmodium falciparum Infection

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