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TNF-R1 Correlates with Cerebral Perfusion and Acute Ischemia Following Subarachnoid Hemorrhage

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An Invited Commentary to this article was published on 15 September 2020

Abstract

Background

Early cerebral hypoperfusion and ischemia occur after subarachnoid hemorrhage (SAH) and influence clinical prognosis. Pathophysiological mechanisms possibly involve inflammatory mediators. TNF-α has been associated with complications and prognosis after SAH. We investigated the relation of perfusion parameters and ischemic lesions, with levels of TNF-α main receptor, TNF-R1, after SAH, and their association with prognosis.

Methods

We included consecutive SAH patients admitted within the first 72 h of SAH onset. Blood samples were simultaneously collected from a peripheral vein and from the parent artery of the aneurysm. Levels of TNF-R1 were measured using ELISA (R&D Systems Inc., USA). CT perfusion and MRI studies were performed in the first 72 h. Correlation and logistic regression analysis were used to identify outcome predictors.

Results

We analyzed 41 patients. Increased levels of TNF-R1 correlated with increased Tmax (arterial: r = −0.37, p = 0.01) and prolonged MTT (arterial: r = 0.355, p = 0.012; venous: r = 0.306, p = 0.026). Increased levels of both arterial and venous TNF-R1 were associated with increased number of lesions on DWI (p = 0.006). In multivariate analysis, venous TNFR1 levels > 1742.2 pg/mL (OR 1.78; 95%CI 1.18–2.67; p = 0.006) and DWI lesions (OR 14.01; 95%CI 1.19–165.3; p = 0.036) were both independent predictors of poor outcome (mRS ≥ 3) at 6 months.

Conclusion

Increased levels of TNF-R1 in arterial and venous blood correlate with worse cerebral perfusion and with increased burden of acute ischemic lesions in the first 72 h after SAH. Venous levels of TNF-R1 and DWI lesions were associated with poor outcome at 6 months. These results highlight the pathophysiological role of TNF-α pathways in SAH and suggest a possible role of combined imaging and laboratorial markers in determining prognosis in acute SAH.

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Acknowledgements

We thank the Clinical Pathology Laboratory of Hospital São José, CHLC, for careful preparation of the blood samples.

Funding

Dr Fragata was supported by Sociedade Portuguesa de AVC/Tecnifar. Dr Bustamante is supported by a Juan Rodes research contract (JR16/00008) from Instituto de Salud Carlos III.

Author information

Authors and Affiliations

  1. Neuroradiology Department, Centro Hospitalar Lisboa Central, Rua Jose Antonio Serrano, 1150-099, Lisbon, Portugal

    Isabel Fragata

  2. Neurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Barcelona, Spain

    Alejandro Bustamante, Ana Penalba & Joan Montaner

  3. Unidade Cérebro-Vascular, Centro Hospitalar Lisboa Central, Lisbon, Portugal

    Patrícia Ferreira & Ana Paiva Nunes

  4. Department of Neurosciences and Mental Health (Neurology), Hospital de Santa Maria, Lisbon, Portugal

    Patrícia Canhão

  5. Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal

    Patrícia Canhão

  6. Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain

    Joan Montaner

  7. Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain

    Joan Montaner

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  1. Isabel Fragata
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Contributions

IF, AB, PC, JM contributed to project design; IF, AB, AP, PF, APN contributed to data collection; AB, IF performed data analysis; IF, AB, JM, PC contributed to writing. All authors reviewed and approved the final manuscript.

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Correspondence to Isabel Fragata.

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Fragata, I., Bustamante, A., Penalba, A. et al. TNF-R1 Correlates with Cerebral Perfusion and Acute Ischemia Following Subarachnoid Hemorrhage. Neurocrit Care 33, 679–687 (2020). https://doi.org/10.1007/s12028-020-01082-3

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  • DOI: https://doi.org/10.1007/s12028-020-01082-3

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