Skip to main content

Advertisement

Log in

Serum B cell lymphoma-2 concentrations and mortality of patients with spontaneous intracerebral hemorrhage

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Objective

There is scarce data on B cell lymphoma 2 (Bcl2), a member of the Bcl-2 family of antiapoptotic molecules of the intrinsic apoptosis pathway, in patients with spontaneous intracerebral hemorrhage (SIH). In one study, higher serum Bcl2 levels were found in patients with SIH than in healthy subjects. Thus, the objective of our study was to compare serum Bcl2 levels in surviving and non-surviving SIH patients.

Methods

Patients with severe supratentorial SIH (defined as Glasgow Coma Scale < 9) admitted from the Intensive Care Units of five Spanish hospitals were included in this observational and prospective study. Serum levels of Bcl2L were determined at the time of diagnosis. Thirty-day mortality was the end-point study.

Results

Non-surviving (n = 38) compared to surviving patients (n = 41) had higher intracerebral hemorrhage (ICH) score (p = 0.001), midline shift (p = 0.003), and serum Bcl2 levels (p < 0.001). In addition, non-surviving compared to surviving patients had lower early hematoma evacuation rate (p = 0.03). We found 77% area under curve in mortality prediction for serum Bcl2 levels (95% CI = 0.66–88%; p < 0.001). Patients showing serum Bcl2 levels > 16.5 ng/mL had higher risk of death according to analysis of Kaplan-Meier (HR = 5.2; 95% CI = 2.5–10.6; p < 0.001). An association, after control for ICH score, midline shift, and early hematoma evacuation, was found between serum Bcl2 levels and 30-day mortality (OR = 1.090; 95% CI = 1.030–1.154; p = 0.003) in the multiple logistic regression.

Conclusions

As far as we know, our study is the first one reporting higher serum Bcl2 levels in non-surviving than in surviving SIH patients and the association between serum Bcl2 levels and SIH mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

APACHE-II:

Acute Physiology and Chronic Health Evaluation

aPTT:

Activated partial thromboplastin time

FIO2 :

Fraction inspired of oxygen

GCS:

Glasgow Coma Scale

ICU:

Intensive Care Unit

INR:

International normalized ratio

ISS:

Injury Severity Score

PaO2 :

Pressure of arterial oxygen

References

  1. Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, Fung GL, Goldstein JN, Macdonald RL, Mitchell PH, Scott PA, Selim MH, Woo D, American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology Guidelines for the Management of Spontaneous Intracerebral Hemorrhage (2015) A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 46:2032–2060

    Article  Google Scholar 

  2. Bobinger T, Burkardt P, Huttner HB, Manaenko A (2018) Programmed cell death after intracerebral hemorrhage. Curr Neuropharmacol 16:1267–1281

    Article  CAS  Google Scholar 

  3. Liao KH, Sung CW, Huang YN, Li WJ, Yu PC, Wang JY (2017) Therapeutic potential of drugs targeting pathophysiology of intracerebral hemorrhage: from animal models to clinical applications. Curr Pharm Des 23:2212–2225

    CAS  PubMed  Google Scholar 

  4. Salihu AT, Muthuraju S, Idris Z, Izaini Ghani AR, Abdullah JM (2016) Functional outcome after intracerebral haemorrhage – a review of the potential role of antiapoptotic agents. Rev Neurosci 27:317–327

    Article  Google Scholar 

  5. Hwang BY, Appelboom G, Ayer A, Kellner CP, Kotchetkov IS, Gigante PR, Haque R, Kellner M, Connolly ES (2011) Advances in neuroprotective strategies: potential therapies for intracerebral hemorrhage. Cerebrovasc Dis 31:211–222

    Article  Google Scholar 

  6. Zhang XQ, Zhang ZM, Yin XL, Zhang K, Cai H, Ling F (2010) Exploring the optimal operation time for patients with hypertensive intracerebral hemorrhage: tracking the expression and progress of cell apoptosis of prehematomal brain tissues. Chin Med J 123:1246–1250

    PubMed  Google Scholar 

  7. Wu CH, Ding XY, Wang HY, Ye XB, Huang SY, Huang AM, Li HZ, Wu SY, Yu J, Yan XH (2006) Neural apoptosis and apoptosis-related genes in intracerebral hemorrhage patients. Zhonghua Yi Xue Za Zhi 86:3073–3076

    CAS  PubMed  Google Scholar 

  8. Wang YX, Yan A, Ma ZH, Wang Z, Zhang B, Ping JL, Zhu JS, Zhou Y, Dai L (2011) Nuclear factor-κB and apoptosis in patients with intracerebral hemorrhage. J Clin Neurosci 18:1392–1395

    Article  Google Scholar 

  9. Bao G, Han Y, Wang M, Xu G (2011) Relationship between cellular apoptosis and the expression of p75 neurotrophin receptor and tyrosine kinase A receptor in tissue surrounding haematoma in intracerebral haemorrhage. J Int Med Res 39:150–160

    Article  CAS  Google Scholar 

  10. Guo FQ, Li XJ, Chen LY, Yang H, Dai HY, Wei YS, Huang YL, Yang YS, Sun HB, Xu YC, Yang ZL (2006) Study of relationship between inflammatory response and apoptosis in perihematoma region inpatients with intracerebral hemorrhage. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 18:290–293

    CAS  PubMed  Google Scholar 

  11. Zhu S, Tang Z, Guo S, Peng L, Fang S, Zhang S (2004) Experimental study on the expression of HIF-1alpha and its relationship to apoptosis in tissues around cerebral bleeding loci. J Huazhong Univ Sci Technolog Med Sci 24:373–375

    Article  CAS  Google Scholar 

  12. Qureshi AI, Suri MF, Ostrow PT, Kim SH, Ali Z, Shatla AA, Guterman LR, Hopkins LN (2003) Apoptosis as a form of cell death in intracerebral hemorrhage. Neurosurgery 52:1041–1047

    PubMed  Google Scholar 

  13. Wu CH, Ding XY, Wang HY, Ye XB, Huang SY, Huang AM, Li HZ, Wu SY, Yu J, Yan XH (2006) Neural apoptosis and apoptosis-related genes in intracerebral hemorrhage patients. Zhonghua Yi Xue Za Zhi 86:3073–3076

    CAS  PubMed  Google Scholar 

  14. Duan SR, Wang XR, Wang CY, Wang DS, Qi JP, Wang HT (2007) Expressions of heme oxygenase-1 and apoptosis-modulating proteins in peri-hematoma cortex after intracerebral hemorrhage in human being. Zhonghua Yi Xue Za Zhi 8:1904–1907

    Google Scholar 

  15. Hu M, Chen YQ, Gong HY (2017) A clinical study on the effects of recombinant human colony stimulating factor on the expression of Bcl-2 in serum of patients with basal ganglia hemorrhage and its clinical significance. Eur Rev Med Pharmacol Sci 21:2895–2900

    CAS  PubMed  Google Scholar 

  16. Teasdale G, Jennett B (1974) Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81–84

    Article  CAS  Google Scholar 

  17. Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829

    Article  CAS  Google Scholar 

  18. Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC (2001) The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 32:891–897

    Article  Google Scholar 

  19. Greenberg SM, Charidimou A (2018) Diagnosis of cerebral amyloid Angiopathy: evolution of the Boston criteria. Stroke 49:491–497

    Article  Google Scholar 

  20. Lee IN, Cheng WC, Chung CY, Lee MH, Lin MH, Kuo CH, Weng HH, Yang JT (2015) Dexamethasone reduces brain cell apoptosis and inhibits inflammatory response in rats with intracerebral hemorrhage. J Neurosci Res 93:178–188

    Article  CAS  Google Scholar 

  21. Zhou F, Liu Y, Yang B, Hu Z (2018) Neuroprotective potential of glibenclamide is mediated by antioxidant and anti-apoptotic pathways in intracerebral hemorrhage. Brain Res Bull 142:18–24

    Article  CAS  Google Scholar 

  22. Gu C, Wu Y, Fan Z, Han W (2018) Simvastatin improves intracerebral hemorrhage through NF-κB-mediated apoptosis via the MyD88/TRIF signaling pathway. Exp Ther Med 15:377–382

    CAS  PubMed  Google Scholar 

  23. Zhao L, Zhang JH, Sherchan P, Krafft PR, Zhao W, Wang S, Chen S, Guo Z, Tang J (2019) Administration of rCTRP9 attenuates neuronal apoptosis through AdipoR1/PI3K/Akt signaling pathway after ICH in mice. Cell Transplant 28:756–766

    Article  Google Scholar 

  24. Xu W, Li T, Gao L, Lenahan C, Zheng J, Yan J, Shao A, Zhang J (2019) Sodium benzoate attenuates secondary brain injury by inhibiting neuronal apoptosis and reducing mitochondria-mediated oxidative stress in a rat model of Intracerebral hemorrhage: possible involvement of DJ-1/Akt/IKK/NFκB pathway. Front Mol Neurosci 12:105

    Article  CAS  Google Scholar 

  25. Xi Z, Hu X, Chen X, Yang Y, Ren J, Wang B, Zhong Z, Sun Y, Yang GY, Sun Q, Bian L (2019) Protocatechuic acid exerts protective effects via suppression of the P38/JNK- NF-κB signalling pathway in an experimental mouse model of intracerebral haemorrhage. Eur J Pharmacol 854:128–138

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by a grant from Instituto de Salud Carlos III (PI-18-00500) (Madrid, Spain) and co-financed with Fondo Europeo de Desarrollo Regional (FEDER). The funding did not influence in the study design, the collection, analysis, and interpretation of data, the manuscript writing, and the decision to submit it for publication.

Author information

Authors and Affiliations

Authors

Contributions

LL was responsible for conceiving, designing, and coordinating the study, made substantial contributions to acquisition of data, analysis, and interpretation of data, and drafted the manuscript.

MMM, LRG, JSV, and JJC have made substantial contributions to acquisition of data and provided useful suggestions.

APC, AFGR, and JJVJ participated in blood determination levels.

AJ have made substantial contributions to analysis and interpretation of data.

All authors read critically and approved the manuscript, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Leonardo Lorente.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethical approval

The protocol was approved by Review Board of the five hospitals participating in the study: H. Universitario Dr. Negrín (Las Palmas de Gran Canaria), H. Universitario Nuestra Señora de Candelaria (Santa Cruz de Tenerife), H. Insular de Las Palmas de Gran Canaria, H. General de La Palma, and H. Universitario de Canarias (La Laguna).

Informed consent

The written signed informed consent was obtained by a family member of each patient.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Key messages

• Non-surviving at 30 days showed higher serum Bcl2 levels than surviving patients.

• There is an association between serum Bcl2 levels and mortality.

• Serum Bcl2 levels could be used as prognostic biomarker mortality.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lorente, L., Martín, M.M., González-Rivero, A.F. et al. Serum B cell lymphoma-2 concentrations and mortality of patients with spontaneous intracerebral hemorrhage. Neurol Sci 42, 3631–3636 (2021). https://doi.org/10.1007/s10072-021-05048-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-021-05048-x

Keywords

Navigation