Roney Santos Coimbra, Bruno Frederico Aguilar Calegare, Talitah Michel Sanchez Candiani, Vânia D'Almeida
{"title":"同型半胱氨酸在儿童急性细菌性脑膜炎病理生理中的推测作用。","authors":"Roney Santos Coimbra, Bruno Frederico Aguilar Calegare, Talitah Michel Sanchez Candiani, Vânia D'Almeida","doi":"10.1186/1472-6890-14-43","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acute bacterial meningitis frequently causes cortical and hippocampal neuron loss leading to permanent neurological sequelae. Neuron death in acute bacterial meningitis involves the excessive activation of NMDA receptors and p53-mediated apoptosis, and the latter is triggered by the depletion of NAD + and ATP cellular stores by the DNA repair enzyme poly(ADP-ribose) polymerase. This enzyme is activated during acute bacterial meningitis in response to DNA damage induced, on its turn, by reactive oxygen and nitrogen species. An excess of homocysteine can also induce this cascade of events in hippocampal neurons. The present work aimed at investigating the possible involvement of homocysteine in the pathophysiology of meningitis by comparing its concentrations in cerebrospinal fluid (CSF) samples from children with viral or acute bacterial meningitis, and control individuals.</p><p><strong>Methods: </strong>Homocysteine and cysteine concentrations were assessed by high-performance liquid chromatography in CSF samples from nine patients with acute bacterial meningitis, 13 patients with viral meningitis and 18 controls (median age: 4 years-old; range: <1 to 13) collected by lumbar puncture at admission at the Children's Hospital Joao Paulo II - FHEMIG, from January 2010 to November 2011.</p><p><strong>Results: </strong>We found that homocysteine accumulates up to neurotoxic levels within the central nervous system of patients with acute bacterial meningitis, but not in those with viral meningitis or control individuals. No correlation was found between homocysteine and cysteine concentrations and the cerebrospinal fluid standard cytochemical parameters.</p><p><strong>Conclusions: </strong>Our results suggest that HCY is produced intrathecally in response to acute bacterial meningitis and accumulates within the central nervous system reaching potentially neurotoxic levels. This is the first work to propose a role for HCY in the pathophysiology of brain damage associated with acute bacterial meningitis.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2014-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6890-14-43","citationCount":"3","resultStr":"{\"title\":\"A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children.\",\"authors\":\"Roney Santos Coimbra, Bruno Frederico Aguilar Calegare, Talitah Michel Sanchez Candiani, Vânia D'Almeida\",\"doi\":\"10.1186/1472-6890-14-43\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Acute bacterial meningitis frequently causes cortical and hippocampal neuron loss leading to permanent neurological sequelae. Neuron death in acute bacterial meningitis involves the excessive activation of NMDA receptors and p53-mediated apoptosis, and the latter is triggered by the depletion of NAD + and ATP cellular stores by the DNA repair enzyme poly(ADP-ribose) polymerase. This enzyme is activated during acute bacterial meningitis in response to DNA damage induced, on its turn, by reactive oxygen and nitrogen species. An excess of homocysteine can also induce this cascade of events in hippocampal neurons. The present work aimed at investigating the possible involvement of homocysteine in the pathophysiology of meningitis by comparing its concentrations in cerebrospinal fluid (CSF) samples from children with viral or acute bacterial meningitis, and control individuals.</p><p><strong>Methods: </strong>Homocysteine and cysteine concentrations were assessed by high-performance liquid chromatography in CSF samples from nine patients with acute bacterial meningitis, 13 patients with viral meningitis and 18 controls (median age: 4 years-old; range: <1 to 13) collected by lumbar puncture at admission at the Children's Hospital Joao Paulo II - FHEMIG, from January 2010 to November 2011.</p><p><strong>Results: </strong>We found that homocysteine accumulates up to neurotoxic levels within the central nervous system of patients with acute bacterial meningitis, but not in those with viral meningitis or control individuals. No correlation was found between homocysteine and cysteine concentrations and the cerebrospinal fluid standard cytochemical parameters.</p><p><strong>Conclusions: </strong>Our results suggest that HCY is produced intrathecally in response to acute bacterial meningitis and accumulates within the central nervous system reaching potentially neurotoxic levels. This is the first work to propose a role for HCY in the pathophysiology of brain damage associated with acute bacterial meningitis.</p>\",\"PeriodicalId\":35804,\"journal\":{\"name\":\"BMC Clinical Pathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2014-11-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1186/1472-6890-14-43\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Clinical Pathology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/1472-6890-14-43\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2014/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Clinical Pathology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/1472-6890-14-43","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2014/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children.
Background: Acute bacterial meningitis frequently causes cortical and hippocampal neuron loss leading to permanent neurological sequelae. Neuron death in acute bacterial meningitis involves the excessive activation of NMDA receptors and p53-mediated apoptosis, and the latter is triggered by the depletion of NAD + and ATP cellular stores by the DNA repair enzyme poly(ADP-ribose) polymerase. This enzyme is activated during acute bacterial meningitis in response to DNA damage induced, on its turn, by reactive oxygen and nitrogen species. An excess of homocysteine can also induce this cascade of events in hippocampal neurons. The present work aimed at investigating the possible involvement of homocysteine in the pathophysiology of meningitis by comparing its concentrations in cerebrospinal fluid (CSF) samples from children with viral or acute bacterial meningitis, and control individuals.
Methods: Homocysteine and cysteine concentrations were assessed by high-performance liquid chromatography in CSF samples from nine patients with acute bacterial meningitis, 13 patients with viral meningitis and 18 controls (median age: 4 years-old; range: <1 to 13) collected by lumbar puncture at admission at the Children's Hospital Joao Paulo II - FHEMIG, from January 2010 to November 2011.
Results: We found that homocysteine accumulates up to neurotoxic levels within the central nervous system of patients with acute bacterial meningitis, but not in those with viral meningitis or control individuals. No correlation was found between homocysteine and cysteine concentrations and the cerebrospinal fluid standard cytochemical parameters.
Conclusions: Our results suggest that HCY is produced intrathecally in response to acute bacterial meningitis and accumulates within the central nervous system reaching potentially neurotoxic levels. This is the first work to propose a role for HCY in the pathophysiology of brain damage associated with acute bacterial meningitis.
期刊介绍:
BMC Clinical Pathology is an open access journal publishing original peer-reviewed research articles in all aspects of histopathology, haematology, clinical biochemistry, and medical microbiology (including virology, parasitology, and infection control). BMC Clinical Pathology (ISSN 1472-6890) is indexed/tracked/covered by PubMed, CAS, EMBASE, Scopus and Google Scholar.