Background: Neonatal bacterial infections have been reported to cause white matter loss, although studies concerning the influence of infection on the expression of myelin and aging are still in their emerging state. Purpose: The present study aimed to investigate the effects of perinatal lipopolysaccharide (LPS) exposure on the myelination at different age points using histochemical and immunocytochemical techniques and the relative motor coordination. Methods: A rat bacterial infection model was established by exposing the neonatal rats with LPS (0.3 mg/kg body weight, i.p., on postnatal day (PND) 3 followed by a booster at PND 5) and its impact was studied on the myelination and motor coordination in young, adult, and senile rats. Results: The results obtained suggest that the administration of LPS induces demyelination, predominantly in cortex and corpus callosum. Low expression level of myelin oligodendrocyte glycoprotein (MOG) was observed at all time points, with prominence at 12, 18, and 24 months of age. In addition, reduced staining with luxol fast blue stain was also recorded in the experimentals. With the increasing demyelination and declining motor ability, LPS exposure also seemed to accelerate normal aging symptoms. Conclusion: There is a direct correlation of myelin damage and poor motor coordination with age. This would provide a better incite to understand inflammation-associated demyelinating changes in age-associated neurodegenerative disorders. Since, no long-term studies on behavioral impairments caused by LPS-induced demyelination in the central nervous system has been reported so far, this work would help in the better understanding of the long-term pathological effects of bacterial-induced demyelination.

Wingerchuk DM, Weinshenker BG: Multiple sclerosis: epidemiology, genetics, classification, natural history, and clinical outcome measures. Neuroimaging Clin N Am 2000;10:611-624, vii.
Fields RD: White matter in learning, cognition and psychiatric disorders. Trends Neurosci 2008;31:361-370.
Bartzokis G: Alzheimer's disease as homeostatic responses to age-related myelin breakdown. Neurobiol Aging 2011;32:1341-1371.
Nave KA: Myelination and support of axonal integrity by glia. Nature 2010;468:244-252.
Bear MF, Connors BW and Paradiso M: Neuroscience-Exploring the Brain, ed 4, pp 103-107, Lippincott Williams & Wilkins, 2016.
Felts PA, Woolston AM, Fernando HB, Asquith S, Gregson NA, Mizzi OJ, Smith KJ: Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide. Brain 2005;128(pt 7):1649-1666.
Brady S, Siegel G, Albers RW, Price D: Basic Neurochemistry: Principles of Molecular, Cellular, and Medical Neurobiology, ed 8. pp 691-704, Academic Press, 2011.
Fernández O, Fernández VE, Guerrero M: Demyelinating diseases of the central nervous system. Medicine 2015;11:4601-4609.
Martin GS: Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes. Expert Rev Anti Infect Ther 2012;10:701-706.
Love S: Demyelinating diseases. J Clin Pathol 2006;59:1151-1159.
Lehnardt S, Massillon L, Follett P, Jensen FE, Ratan R, Rosenberg PA, Volpe JJ, Vartanian T: Activation of innate immunity in the CNS triggers neurodegeneration through a toll-like receptor 4-dependent pathway. Proc Natl Acad Sci U S A 2003;100:8514-8519.
Wang KC, Fan LW, Kaizaki A, Pang Y, Cai Z, Tien LT: Neonatal lipopolysaccharide exposure induces long-lasting learning impairment, less anxiety-like response and hippocampal injury in adult rats. Neuroscience 2013;234:146-157.
Sharma A, Patro N, Patro IK: Lipopolysaccharide-induced apoptosis of astrocytes: therapeutic intervention by minocycline. Cell Mol Neurobiol 2016;36:577-592.
Brites D, Fernandes A: Bilirubin-induced neural impairment: a special focus on myelination, age-related windows of susceptibility and associated co-morbidities. Semin Fetal Neonatal Med 2015;20:14-19.
Wichterman KA, Baue AE, Chaudry IH: Sepsis and septic shock - a review of laboratory models and a proposal. J Surg Res 1980;29:189-201.
Nemzek JA, Hugunin KM, Opp MR: Modeling sepsis in the laboratory: merging sound science with animal well-being. Comp Med 2008;58:120-128.
Cardoso FL, Herz J, Fernandes A, Rocha J, Sepodes B, Brito MA, McGavern DB, Brites D: Systemic inflammation in early neonatal mice induces transient and lasting neurodegenerative effects. J Neuroinflammation 2015;12:82.
Rousset CI, Chalon S, Cantagrel S, Bodard S, Andres C, Gressens P, Saliba E: Maternal exposure to LPS induces hypomyelination in the internal capsule and programmed cell death in the deep gray matter in newborn rats. Pediatr Res 2006;59:428-433.
Lazosky A, Young GB, Zirul S, Phillips R: Quality of life after septic illness. J Crit Care 2010;25:406-412.
Steiner AA, Chakravarty S, Robbins JR, Dragic AS, Pan J, Herkenham M, Romanovsky AA: Thermoregulatory responses of rats to conventional preparations of lipopolysaccharide are caused by lipopolysaccharide per se - not by lipoprotein contaminants. Am J Physiol Regul Integr Comp Physiol 2005;289:R348-R352.
Naik AA, Patro IK, Patro N: Slow physical growth, delayed reflex ontogeny, and permanent behavioral as well as cognitive impairments in rats following intra-generational protein malnutrition. Front Neurosci 2015;9:446.
Kumar K, Patro N, Patro I: Impaired structural and functional development of cerebellum following gestational exposure of deltamethrin in rats: role of reelin. Cell Mol Neurobiol 2013;33:731-746.
Mallard C, Wang X: Infection-induced vulnerability of perinatal brain injury. Neurol Res Int 2012;2012:102153.
Tissières P, Ochoda A, Dunn-Siegrist I, Drifte G, Morales M, Pfister R, Berner M, Pugin J: Innate immune deficiency of extremely premature neonates can be reversed by interferon-γ. PLoS One 2012;7:e32863.
Morell P: Myelin, ed 2. New York, Plenum Press, 1984.
Weberpals M, Hermes M, Hermann S, Kummer MP, Terwel D, Semmler A, Berger M, Schäfers M, Heneka MT: NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits. J Neurosci 2009;29:14177-14184.
Bossù P, Cutuli D, Palladino I, Caporali P, Angelucci F, Laricchiuta D, Gelfo F, De Bartolo P, Caltagirone C, Petrosini L: A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18. J Neuroinflammation 2012;9:101.
Anderson ST, Commins S, Moynagh PN, Coogan AN: Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse. Brain Behav Immun 2015;43:98-109.
Leviton A, Gressens P: Neuronal damage accompanies perinatal white-matter damage. Trends Neurosci 2007;30:473-478.
Strunk T, Inder T, Wang X, Burgner D, Mallard C, Levy O: Infection-induced inflammation and cerebral injury in preterm infants. Lancet Infect Dis 2014;14:751-762.
Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H: Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000;47:707-717.
Aboul-Enein F, Rauschka H, Kornek B, Stadelmann C, Stefferl A, Brück W, et al: Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases. J Neuropathol Exp Neurol 2003;62:25-33.
Boehm SL 2nd, Schafer GL, Phillips TJ, Browman KE, Crabbe JC: Sensitivity to ethanol-induced motor incoordination in 5-HT(1B) receptor null mutant mice is task-dependent: implications for behavioral assessment of genetically altered mice. Behav Neurosci 2000;114:401-409.
Rustay NR, Wahlsten D, Crabbe JC: Influence of task parameters on rotarod performance and sensitivity to ethanol in mice. Behav Brain Res 2003;141;237-249.
Lipp HP, Wahlsten D: Absence of the Corpus Callosum. Genetically Defined Animal Models of Neurobehavioral Dysfunctions, ed 1. Boston, Birkhäuser, 1992, pp 217-252.
Nagayach A, Patro N, Patro I: Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function. Front cell Neurosci 2014;8:355.
Serra-de-Oliveira N, Boilesen SN, Prado de França Carvalho C, LeSueur-Maluf L, Zollner Rde L, Spadari RC, Medalha CC, Monteiro de Castro G: Behavioural changes observed in demyelination model shares similarities with white matter abnormalities in humans. Behav Brain Res 2015;287:265-275.
Volpe JJ: Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol 2009;8:110-124.
Ferrari F, Todeschini A, Guidotti I, Martinez-Biarge M, Roversi MF, Berardi A, Ranzi A, Cowan FM, Rutherford MA: General movements in full-term infants with perinatal asphyxia are related to basal ganglia and thalamic lesions. J Pediatr 2011;158:904-911.
Franklin RJ, Zhao C, Sim FJ: Ageing and CNS remyelination. Neuroreport 2002;13:923-928.
Sim FJ, Zhao C, Penderis J, Franklin RJ: The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci 2002;22:2451-2459.
Altmann-Schneider I, de Craen AJ, van den Berg-Huysmans AA, Slagboom P, Westendorp RG, van Buchem MA, van der Grond J: An in vivo study on brain microstructure in biological and chronological ageing. PLoS One 2015;10:e0120778.
Sherin JE, Bartzokis G: Human brain myelination trajectories across the life span: implications for CNS function and dysfunction; in Masoro EJ, Austa SN (eds): Handbook of the Biology of Aging, ed 7. San Diego, Academic Press, 2011, pp 333-346.
Xie F, Zhang JC, Fu H, Chen J: Age-related decline of myelin proteins is highly correlated with activation of astrocytes and microglia in the rat CNS. Int J Mol Med 2013;32:1021-1028.
Franco-Pons N, Torrente M, Colomina MT, Vilella E: Behavioral deficits in the cuprizone-induced murine model of demyelination/remyelination. Toxicol Lett 2007;169:205-213.
Torkildsen Ø, Brunborg LA, Myhr KM, Bø L: The cuprizone model for demyelination. Acta Neurol Scand Suppl 2008;188:72-76.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.