A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children.

Q2 Medicine
BMC Clinical Pathology Pub Date : 2014-11-22 eCollection Date: 2014-01-01 DOI:10.1186/1472-6890-14-43
Roney Santos Coimbra, Bruno Frederico Aguilar Calegare, Talitah Michel Sanchez Candiani, Vânia D'Almeida
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引用次数: 3

Abstract

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.

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。
背景:急性细菌性脑膜炎经常引起皮层和海马神经元的丢失,导致永久性的神经系统后遗症。急性细菌性脑膜炎的神经元死亡涉及NMDA受体的过度激活和p53介导的细胞凋亡,后者是由DNA修复酶聚核糖(adp -核糖)聚合酶耗尽NAD +和ATP细胞储存引发的。这种酶在急性细菌性脑膜炎期间被激活,以应对由活性氧和活性氮引起的DNA损伤。过量的同型半胱氨酸也能在海马神经元中诱发这种级联反应。本研究旨在通过比较病毒性或急性细菌性脑膜炎患儿和对照个体脑脊液样本中同型半胱氨酸的浓度,探讨同型半胱氨酸在脑膜炎病理生理中的可能参与。方法:采用高效液相色谱法对9例急性细菌性脑膜炎患者、13例病毒性脑膜炎患者和18例对照组(中位年龄:4岁;结果:我们发现同型半胱氨酸在急性细菌性脑膜炎患者的中枢神经系统中积累到神经毒性水平,但在病毒性脑膜炎患者或对照个体中没有。同型半胱氨酸和半胱氨酸浓度与脑脊液标准细胞化学参数之间没有相关性。结论:我们的研究结果表明,HCY在急性细菌性脑膜炎的鞘内产生,并在中枢神经系统内积累,达到潜在的神经毒性水平。这是首次提出HCY在急性细菌性脑膜炎相关脑损伤病理生理学中的作用。
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来源期刊
BMC Clinical Pathology
BMC Clinical Pathology Medicine-Pathology and Forensic Medicine
CiteScore
3.30
自引率
0.00%
发文量
0
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.
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