Background
Attempts to clarify mechanisms of early brain injury in subarachnoid hemorrhage (SAH)
revealed a high-mobility group box 1 (HMGB1) protein involvement in sterile inflammation
initiated by aneurysm rupture. This study aims at assessing the prognostic value of
HMGB1 in comparison with traditional biomarkers.
Methods
Ten patients with Fisher grade 4 SAH and acute hydrocephalus underwent endovascular
coiling and ventriculostomy. HMGB1 level was measured in cerebrospinal fluid (CSF)
samples collected on first, fifth, and 10th day. HMGB1 level in first sample was correlated
with treatment outcome assessed in Glasgow outcome scale (GOS) at 3 months. Obtained
results were compared with plasma inflammatory markers, clinical grading scales, and
imaging grading scales. HMGB1 level in consecutive samples was analyzed in search
of concentration trends correlating with patients' outcome.
Results
HMGB1 level in CSF of SAH patients, in contrast to control group, is significantly
elevated (P < .001). Good (GOS > 3) and poor (GOS ≤ 3) outcome patients differ significantly
in HMGB1 level on admission (P < .01). The strongest correlation to patients' outcome was found for Hunt and Hess
scale (R = −.887, P < .01), HMGB1 level (R = −.859, P < .01), and World Federation of Neurological Surgeons scale (R = −.832, P < .01). Constant and high HMGB1 level of 10 ng/mL or more in consecutive CSF samples
identifies nonsurvivors.
Conclusions
HMGB1 protein is elevated in SAH patients. Changes in the concentration of HMGB1 in
consecutive samples of the CSF correlate with outcome. Our results encourage further
proteomic investigation.
Key Words
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References
- The importance of early brain injury after subarachnoid hemorrhage.Prog Neurobiol. 2012; 97: 14-37
- Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group.Stroke. 2010; 41: 2391-2395
- To look beyond vasospasm in aneurysmal subarachnoid haemorrhage.Biomed Res Int. 2014; 2014: 628597
- Metamorphosis of subarachnoid hemorrhage research: from delayed vasospasm to early brain injury.Mol Neurobiol. 2011; 43: 27-40
- Elucidating novel mechanisms of brain injury following subarachnoid hemorrhage: an emerging role for neuroproteomics.Neurosurg Focus. 2010; 28: E10
- In-depth characterization of the cerebrospinal fluid proteome displayed through the CSF Proteome Resource (CSF-PR).Mol Cell Proteomics. 2014; 13: 3152-3163
- HMGB1 is a therapeutic target for sterile inflammation and infection.Annu Rev Immunol. 2011; 29: 139-162
- High-mobility group box 1 promotes metalloproteinase-9 upregulation through Toll-like receptor 4 after cerebral ischemia.Stroke. 2010; 41: 2077-2082
- High-mobility group box 1 protein in CSF of patients with subarachnoid hemorrhage.Neurocrit Care. 2009; 11: 362-368
- Relationship between plasma high mobility group box-1 protein levels and clinical outcomes of aneurysmal subarachnoid hemorrhage.J Neuroinflammation. 2012; 9: 194
- Extent of acute hydrocephalus after subarachnoid hemorrhage as a risk factor for poor functional outcome.Neurol Res. 2013; 35: 107-110
- Intraventricular hemorrhage after aneurysmal subarachnoid hemorrhage: pilot study of treatment with intraventricular tissue plasminogen activator.Neurosurgery. 2005; 56 (discussion 205-213): 205-213
- Relation among aneurysm size, amount of subarachnoid blood, and clinical outcome.J Neurosurg. 2007; 107: 13-17
- Prognostic factors for outcome in patients with aneurysmal subarachnoid hemorrhage.Stroke. 2007; 38: 2315-2321
- Predicting long-term outcome in poor grade aneurysmal subarachnoid haemorrhage patients utilising the Glasgow Coma Scale.J Clin Neurosci. 2009; 16: 26-31
- Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive meta-analysis.Stroke. 2008; 39: 3029-3035
- Serum C-reactive protein levels predict neurological outcome after aneurysmal subarachnoid hemorrhage.Arq Neuropsiquiatr. 2011; 70: 202-205
- The blood leukocyte count and its prognostic significance in subarachnoid hemorrhage.J Neurosurg Sci. 1987; 31: 45-48
- A study of blood coagulation and fibrinolytic system in spontaneous outcome.Surg Neurol. 2001; 3019: 197-203
- Higher hemoglobin is associated with less cerebral infarction, poor outcome, and death after subarachnoid hemorrhage.Neurosurgery. 2006; 59 (discussion 779-780): 775-779
- A comparison of 3 radiographic scales for the prediction of delayed ischemia and prognosis following subarachnoid hemorrhage.J Neurosurg. 2008; 109: 199-207
- Early release of high-mobility group box 1 (HMGB1) from neurons in experimental subarachnoid hemorrhage in vivo and in vitro.J Neuroinflammation. 2014; 11: 106
- Biphasic actions of HMGB1 signaling in inflammation and recovery after stroke.Ann N Y Acad Sci. 2010; 1207: 50-57
- High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo.J Neurochem. 2007; 103: 590-603
- High-mobility group protein box-1 and its relevance to cerebral ischemia.J Cereb blood flow Metab. 2010; 30: 243-254
- Endovascular treatment strategies for acute ischemic stroke.Int J Stroke. 2011; 6: 511-522
- Activation of nuclear factor-κB in the brain after experimental subarachnoid hemorrhage and its potential role in delayed brain injury.PLoS One. 2013; 8: e60290
- Increase ICAM-1 and LFA-1 expression by cerebrospinal fluid of subarachnoid hemorrhage patients: involvement of TNF-α.Brain Res. 2013; 1512: 89-96
Article info
Publication history
Published online: June 03, 2015
Accepted:
May 1,
2015
Received in revised form:
April 27,
2015
Received:
December 13,
2014
Footnotes
The authors received grant support from the National Centre for Research and Development, Applied Research Programme, The National Centre of Research and Development No PBSll/9ll3l20l2 “Nanomaterials and their potential biomedical applications.”
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.05.002
Copyright
© 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
