Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage

Kuo Chuan Wang, Sung Chun Tang, Jing Er Lee, Yu I. Li, Yi Shuian Huang, Wei Shiung Yang, Jiann Shing Jeng, Thiruma V. Arumugam, Yong Kwang Tu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 ± 19 years) with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005-1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.

Original languageEnglish
Pages (from-to)435-443
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number2
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Keywords

  • Cell death mechanisms
  • cerebrospinal fluid
  • inflammation
  • receptors
  • subarachnoid hemorrhage

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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