Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy

Meregalli, C; Fumagalli, G; Alberti, Paola; Canta, A; Carozzi, Valentina Alda; Chiorazzi, A; Monza, L; Pozzi, E; Sandelius, Åsa; Blennow, Kaj; Zetterberg, Henrik; Marmiroli, P; Cavaletti, Guido

doi:10.1016/j.expneurol.2018.06.005

Cited by 61 publications

(61 citation statements)

References 11 publications

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“…While the main source of NfL is considered to be the central nervous system, peripheral damage may contribute to increased NfL values as well, as recently revealed by studies on peripheral neuropathies ( 25 , 26 ). Increased blood levels of the muscle enzyme creatine kinase in newborn infants after vaginal deliveries compared to cesarean sections have been reported ( 27 ).…”

Section: Discussionmentioning

confidence: 97%

Neurofilament Light Chain: Blood Biomarker of Neonatal Neuronal Injury

et al. 2018

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Background: Neurofilament light chain (NfL) is a highly promising biomarker of neuroaxonal injury that has mainly been studied in adult neurodegenerative disease. Its involvement in neonatal disease remains largely unknown. Our aim was to establish NfL plasma concentrations in preterm and term infants in the first week of life.Methods: Plasma NfL was measured by single molecule array immunoassay in two neonatal cohorts: cohort 1 contained 203 term and preterm infants, median gestational age (GA) 37.9 weeks (interquartile range [IQR] 31.9–39.4), in whom venous and arterial umbilical cord blood was sampled at birth and venous blood at day of life (DOL) 3; cohort 2 contained 98 preterm infants, median GA 29.3 weeks (IQR 26.9–30.6), in whom venous blood was sampled at DOL 7.Results: Median NfL concentrations in venous blood increased significantly from birth (18.2 pg/mL [IQR 12.8–30.8, cohort 1]) to DOL 3 (50.9 pg/mL [41.3–100, cohort 1]) and DOL 7 (126 pg/mL [78.8–225, cohort 2]) (p < 0.001). In both cohorts NfL correlated inversely with birth weight (BW, Spearman's rho −0.403, p < 0.001, cohort 1; R −0.525, p < 0.001, cohort 2) and GA (R −0.271, p < 0.001, cohort 1; R −0.487, p < 0.001, cohort 2). Additional significant correlations were found for maternal age at delivery, preeclampsia, delivery mode, 5-min Apgar, duration of oxygen supplementation, sepsis, and brain damage (intraventricular hemorrhage or periventricular leukomalacia). Multivariable logistic regression analysis identified the independent predictors of NfL in cohort 1 as BW (beta = −0.297, p = 0.003), delivery mode (beta = 0.237, p = 0.001) and preeclampsia (beta = 0.183, p = 0.022) and in cohort 2 as BW (beta = −0.385, p = 0.001) and brain damage (beta = 0.222, p = 0.015).Conclusion: Neonatal NfL levels correlate inversely with maturity and BW, increase during the first days of life, and relate to brain injury factors such as intraventricular hemorrhage and periventricular leukomalacia, and also to vaginal delivery.

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Section: Discussionmentioning

confidence: 97%

Neurofilament Light Chain: Blood Biomarker of Neonatal Neuronal Injury

et al. 2018

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“…Hopefully, in the nearby future, new diagnostic tools may become available. Recently, attention has been paid to neurofilament light chain as potential marker of peripheral nerve damage both in the preclinical and clinical setting . A possible diagnostic and prognostic role of neurofilaments in the polyneuropathies workup is currently under investigation.…”

Section: Discussionmentioning

confidence: 99%

Peripheral nervous system involvement in lymphomas

Briani

Visentin

Campagnolo

et al. 2019

J Peripheral Nervous Sys

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The peripheral nervous system may be involved at any stage in the course of lymphoproliferative diseases. The different underlying mechanisms include neurotoxicity secondary to chemotherapy, direct nerve infiltration (neurolymphomatosis), infections, immune‐mediated, paraneoplastic or metabolic processes and nutritional deficiencies. Accordingly, the clinical features are heterogeneous and depend on the localization of the damage (ganglia, roots, plexi, and peripheral nerves) and on the involved structures (myelin, axon, and cell body). Some clinical findings, such a focal or diffuse involvement, symmetric or asymmetric pattern, presence of pain may point to the correct diagnosis. Besides a thorough medical history and neurological examination, neurophysiological studies, cerebrospinal fluid analysis, nerve biopsy (in selected patients with suspected lymphomatous infiltration) and neuroimaging techniques (magnetic resonance neurography and nerve ultrasound) may be crucial for a proper diagnostic workup.

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“…Morphological analysis was performed on 1 μm-thick methylene blue stained semithin sections using a Nikon Eclipse E200 light microscope (Leica Microsystems GmbH, Wetzlar, Germany). For IENF density assessment, a previously published method was followed [ 18 ]. Punch biopsy (3 mm) from one hind-paw of each animal was collected after sacrifice.…”

Section: Methodsmentioning

confidence: 99%

Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity

et al. 2020

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Oxaliplatin (OHP) is an antineoplastic compound able to induce peripheral neurotoxicity. Oxidative stress has been suggested to be a key factor in the development of OHP-related peripheral neurotoxicity. Mangafodipir, a contrast agent possessing mitochondrial superoxide dismutase (MnSOD)-mimetic activity, has been tested as a cytoprotector in chemotherapy-induced peripheral neurotoxicity (CIPN). Calmangafodipir (PledOx®) has even better therapeutic activity. We investigated a BALB/c mouse model of OHP-related CIPN and the effects of the pre-treatment of calmangafodipir (2.5, 5, or 10 mg/kg intravenously) on sensory perception, and we performed a pathological study on skin biopsies to assess intraepidermal nerve fiber (IENF) density. At the end of the treatments, OHP alone or in pre-treatment with calmangafodipir 2.5 and 10 mg/kg, induced mechanical allodynia and cold thermal hyperalgesia, but calmangafodipir 5 mg/kg prevented these effects. Accordingly, OHP alone or in pre-treatment with calmangafodipir 2.5 and 10 mg/kg, induced a significant reduction in IENF density, but calmangafodipir 5 mg/kg prevented this reduction. These results confirm a protective effect of calmangafodipir against OHP-induced small fiber neuropathy. Interestingly, these results are in agreement with previous observations suggesting a U-shaped effect of calmangafodipir, with the 10 mg/kg dose less effective than the lower doses.

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Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy

Cited by 61 publications

References 11 publications

Neurofilament Light Chain: Blood Biomarker of Neonatal Neuronal Injury

Neurofilament Light Chain: Blood Biomarker of Neonatal Neuronal Injury

Peripheral nervous system involvement in lymphomas

Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity

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