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Expression and Role of Neuroglobin in Rats With Sepsis-Associated Encephalopathy*

Zhang, Li-Na PhD; Ai, Yu-Hang PhD; Gong, Hua PhD; Guo, Qu-Lian PhD; Huang, Li MD; Liu, Zhi-Yong MD; Yao, Bo MD

doi: 10.1097/CCM.0b013e3182a63b1a
Online Laboratory Investigations

Objectives: To determine the role of neuroglobin in the pathology of sepsis-associated encephalopathy and ascertain if neuroglobin has any protective effects against sepsis-associated encephalopathy.

Design: Randomized laboratory animal study.

Setting: Research university animal laboratory.

Subjects: Two hundred and forty adult male Sprague-Dawley rats.

Interventions: Rats received cecal puncture and ligation (or sham) surgery to induce sepsis, then broken up into groups based on whether or not the rat developed sepsis-associated encephalopathy as determined by electroencephalograph and evoked potential recordings. The rats were then left untreated to examine the effect of sepsis-associated encephalopathy on neuroglobin, treated with a neuroglobin antisense nucleotide to block gene expression, or given hemin, a neuroglobin inducer.

Measurements and Main Results: Following sepsis induction, diagnosis, and treatment, the brains were analyzed for both gross and ultrastructural morphology. Also, neuronal neuroglobin immunoreactivity and apoptosis (via terminal uridine nucleotide end-labeling) were examined. Blood serum levels were then analyzed for neuroglobin, superoxide dismutase, and malondialdehyde levels. We determined that sepsis-associated encephalopathy induces damage evident when examining both gross and ultrastructural morphology, as well as induces neuronal neuroglobin expression. Also, blockade of neuroglobin expression via antisense treatment will exacerbate these pathological effects, while increasing neuroglobin levels via hemin will ameliorate them. Blood analysis found that levels of superoxide dismutase and malondialdehyde mirrored the level of pathology found in the brain, while plasma neuroglobin levels reflected the amount of neuronal neuroglobin immunoreactivity.

Conclusions: We conclude that neuroglobin is involved in the pathogenesis of sepsis-associated encephalopathy and has neuroprotective effects. We also determined that hemin has protective effects against sepsis-associated encephalopathy as well, most probably due to its effect on neuroglobin.

All authors: Department of Intensive Care Unit, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

* See also p. 218.

Supported, in part, by the grants from the Science and Technology Plan Foundation of Hunan Province (No. 2011FJ6030) and the National Clinical Specialty Construction Project of the Health Ministry (No. [2011]1).

The authors have disclosed that they do not have any potential conflicts of interest.

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© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins