Research Article
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Inflammation and Apoptosis-Related Damage in Lung, Liver, and Kidney Tissues due to Subarachnoidal Hemorrhage

Year 2024, Volume: 31 Issue: 4, 310 - 317, 26.12.2024
https://doi.org/10.17343/sdutfd.1482851

Abstract

Objective: Oxidant and inflammatory substances released into the blood due to subarachnoidal hemorrhage (SAH) can pass into the peripheral compartment, causing distant organ damage due to blood-brain barrier permeability caused by oxidative stress, inflammation, and apoptosis. This study aimed to demonstrate the secondary damage to peripheral organs, including the lung, kidney, and liver, resulting from SAH.
Material and Method: Twenty rats were divided into sham and SAH groups, each consisting of ten animals. In the SAH group animals, 0.3 mL autologous blood taken from the tail artery was injected into the cisterna magna for 2 minutes. Seven days after SAH formation, all animals were euthanized under anesthesia. Following decapitation, brain tissues, lung, liver, and kidney tissues were placed in 10% formaldehyde for histopathological and immunohistochemical analysis.
Results: In the SAH group, neuronal degeneration in the cerebral cortex, and hyperemia and hemorrhage in the lung, kidney, and liver were observed histopathologically. In immunohistochemical examinations, decreased expression of brain-derived neurotrophic factor (BDNF) and neurofilament (NF) in the cerebral cortex, cerebellum, and hippocampus sections; In lung tissues, enhanced caspase (Cas)-3, hypoxia-inducible factor 1 alpha (Hif-1α) and nuclear factor kappa beta (NF-κB) expressions in the lung, Cas-5, cyclooxygenase-1 (Cox-1) and interleukin (IL)-1 expressions in the liver, Cas-3, Cox-1 and IL-3 expressions in the kidney were observed.
Conclusion: Following SAH, in addition to damage to brain tissue, peripheral tissues such as the lung, kidney, and liver can also be damaged through inflammation and apoptosis.

Ethical Statement

In this study, all experiments were performed under the guidelines for animal research from the National Institutes of Health and were approved by the Committee on Animal Research of Mehmet Akıf Ersoy University, Burdur (Ethic No:24.04.2024/122-1298).

Supporting Institution

This study was supported by the Suleyman Demirel University Scientific Research Projects Coordination Unit (Project code: TSG-2022-8783).

Project Number

TSG-2022-8783

References

  • 1. Van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid hemorrhage. The Lancet 2007;369(9558):306-18.
  • 2. Tujjar O, Belloni I, Hougardy J-M, Scolletta S, Vincent J-L, Creteur J, Taccone FS. Acute kidney injury after subarachnoid hemorrhage. Journal of Neurosurgical Anesthesiology 2017;29(2):140-9.
  • 3. Mukandala G, Tynan R, Lanigan S, O’Connor JJ. The effects of hypoxia and inflammation on synaptic signaling in the CNS. Brain Sciences 2016;6(1):6.
  • 4. Nguyen A, Patel AB, Kioutchoukova IP, Diaz MJ, Lucke-Wold B. Mechanisms of mitochondrial oxidative stress in Brain Injury: from pathophysiology to therapeutics. Oxygen 2023;3(2):163-78.
  • 5. Zhao Y, Gan L, Ren L, Lin Y, Ma C, Lin X. Factors influencing the blood-brain barrier permeability. Brain Research 2022;1788:147937.
  • 6. Wang Z, Zhou F, Dou Y, Tian X, Liu C, Li H, et al. Melatonin alleviates intracerebral hemorrhage-induced secondary brain injury in rats via suppressing apoptosis, inflammation, oxidative stress, DNA damage, and mitochondria injury. Translational Stroke Research 2018;9:74-91.
  • 7. Senol N, Oguzoglu AS, Erzurumlu Y, Ascı H, Savran M, Gulle K, et al. Modulation of salubrinal-mediated endoplasmic reticulum stress in an experimental subarachnoid hemorrhage model. World Neurosurgery 2021;153:e488-e96.
  • 8. Chen S, Li Q, Wu H, Krafft PR, Wang Z, Zhang JH. The harmful effects of subarachnoid hemorrhage on extracerebral organs. BioMed Research is International 2014;2014(1):858496.
  • 9. Bernardo-Castro S, Sousa JA, Brás A, Cecília C, Rodrigues B, Almendra L, et al. Pathophysiology of blood-brain barrier permeability throughout the different stages of ischemic stroke and its implication on hemorrhagic transformation and recovery. Frontiers in Neurology 2020;11:594672.
  • 10. Jiang X, Andjelkovic AV, Zhu L, Yang T, Bennett MV, Chen J, et al. Blood-brain barrier dysfunction and recovery after ischemic stroke. Progress in Neurobiology 2018;163:144-71.
  • 11. Han DW, Oh JE, Lim BJ, Han Y, Song Y. Dexmedetomidine attenuates subarachnoid hemorrhage-induced acute lung injury through regulating autophagy and TLR/NFκB signaling pathway. Korean J Anesthesiol 2022;75:518-29.
  • 12. Li T, Wang P, Gong X, Chong W, Hai Y, You C, et al. Prevalence and prognostic significance of liver fibrosis in patients with aneurysmal subarachnoid hemorrhage. Frontiers in Neurology 2022;13:850405.
  • 13. Mobed A, Charsouei S, Yazdani Y, Gargari MK, Ahmadalipour A, Sadremousavi SR, et al. Biosensors, recent advances in the determination of BDNF and NfL. Cellular and Molecular Neurobiology 2023;43(8):3801-14.
  • 14. Zhou J, Guo P, Guo Z, Sun X, Chen Y, Feng H. Fluid metabolic pathways after subarachnoid hemorrhage. Journal of Neurochemistry 2022;160(1):13-33.
  • 15. Alfonso M, Aftab S, Hamadneh T, Sherali N, Tsouklidis N. Understanding cognitive deficit after subarachnoid hemorrhage: a memory focused approach. Cureus 2020;12(11).
  • 16. Chen H, Dang Y, Liu X, Ren J, Wang H. Exogenous brain‑derived neurotrophic factor attenuates neuronal apoptosis and neurological deficits after subarachnoid hemorrhage in rats. Experimental and Therapeutic Medicine 2019;18(5):3837-44.
  • 17. Demedts IK, Demoor T, Bracke KR, Joos GF, Brusselle GG. Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. Respiratory Research 2006;7:1-10.
  • 18. Suresh MV, Yalamanchili G, Rao TC, Aktay S, Kralovich A, Shah YM, Raghavendran K. Hypoxia‐inducible factor (HIF)‐1α‐induced regulation of lung injury in pulmonary aspiration is mediated through NF‐kB. FASEB BioAdvances 2022;4(5):309.
  • 19. Sargon MF. Lungs and hypoxia: a review of the literature. Anatomy 2021;15(1):76-83.
  • 20. Pereira M, Liang J, Edwards-Hicks J, Meadows AM, Hinz C, Liggi S, et al. Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting. Cell Reports 2024;43(2).
  • 21. Galea J, Ogungbenro K, Hulme S, Patel H, Scarth S, Hoadley M, et al. Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study. Journal of Neurosurgery 2017;128(2):515-23.
  • 22. Hvas C, Nørregaard R, Nielsen T, Barklin A, Tønnesen E. Brain death increases COX‐1 and COX‐2 expression in the renal medulla in a pig model. Acta Anaesthesiologica Scandinavica 2014;58(2):243-50.
  • 23. Priante G, Gianesello L, Ceol M, Del Prete D, Anglani F. Cell death in the kidney. International Journal of Molecular Sciences 2019;20(14):3598.
  • 24. Ratliff BB, Abdulmahdi W, Pawar R, Wolin MS. Oxidant mechanisms in renal injury and disease. Antioxidants & Redox Signaling 2016;25(3):119-46.
Year 2024, Volume: 31 Issue: 4, 310 - 317, 26.12.2024
https://doi.org/10.17343/sdutfd.1482851

Abstract

Project Number

TSG-2022-8783

References

  • 1. Van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid hemorrhage. The Lancet 2007;369(9558):306-18.
  • 2. Tujjar O, Belloni I, Hougardy J-M, Scolletta S, Vincent J-L, Creteur J, Taccone FS. Acute kidney injury after subarachnoid hemorrhage. Journal of Neurosurgical Anesthesiology 2017;29(2):140-9.
  • 3. Mukandala G, Tynan R, Lanigan S, O’Connor JJ. The effects of hypoxia and inflammation on synaptic signaling in the CNS. Brain Sciences 2016;6(1):6.
  • 4. Nguyen A, Patel AB, Kioutchoukova IP, Diaz MJ, Lucke-Wold B. Mechanisms of mitochondrial oxidative stress in Brain Injury: from pathophysiology to therapeutics. Oxygen 2023;3(2):163-78.
  • 5. Zhao Y, Gan L, Ren L, Lin Y, Ma C, Lin X. Factors influencing the blood-brain barrier permeability. Brain Research 2022;1788:147937.
  • 6. Wang Z, Zhou F, Dou Y, Tian X, Liu C, Li H, et al. Melatonin alleviates intracerebral hemorrhage-induced secondary brain injury in rats via suppressing apoptosis, inflammation, oxidative stress, DNA damage, and mitochondria injury. Translational Stroke Research 2018;9:74-91.
  • 7. Senol N, Oguzoglu AS, Erzurumlu Y, Ascı H, Savran M, Gulle K, et al. Modulation of salubrinal-mediated endoplasmic reticulum stress in an experimental subarachnoid hemorrhage model. World Neurosurgery 2021;153:e488-e96.
  • 8. Chen S, Li Q, Wu H, Krafft PR, Wang Z, Zhang JH. The harmful effects of subarachnoid hemorrhage on extracerebral organs. BioMed Research is International 2014;2014(1):858496.
  • 9. Bernardo-Castro S, Sousa JA, Brás A, Cecília C, Rodrigues B, Almendra L, et al. Pathophysiology of blood-brain barrier permeability throughout the different stages of ischemic stroke and its implication on hemorrhagic transformation and recovery. Frontiers in Neurology 2020;11:594672.
  • 10. Jiang X, Andjelkovic AV, Zhu L, Yang T, Bennett MV, Chen J, et al. Blood-brain barrier dysfunction and recovery after ischemic stroke. Progress in Neurobiology 2018;163:144-71.
  • 11. Han DW, Oh JE, Lim BJ, Han Y, Song Y. Dexmedetomidine attenuates subarachnoid hemorrhage-induced acute lung injury through regulating autophagy and TLR/NFκB signaling pathway. Korean J Anesthesiol 2022;75:518-29.
  • 12. Li T, Wang P, Gong X, Chong W, Hai Y, You C, et al. Prevalence and prognostic significance of liver fibrosis in patients with aneurysmal subarachnoid hemorrhage. Frontiers in Neurology 2022;13:850405.
  • 13. Mobed A, Charsouei S, Yazdani Y, Gargari MK, Ahmadalipour A, Sadremousavi SR, et al. Biosensors, recent advances in the determination of BDNF and NfL. Cellular and Molecular Neurobiology 2023;43(8):3801-14.
  • 14. Zhou J, Guo P, Guo Z, Sun X, Chen Y, Feng H. Fluid metabolic pathways after subarachnoid hemorrhage. Journal of Neurochemistry 2022;160(1):13-33.
  • 15. Alfonso M, Aftab S, Hamadneh T, Sherali N, Tsouklidis N. Understanding cognitive deficit after subarachnoid hemorrhage: a memory focused approach. Cureus 2020;12(11).
  • 16. Chen H, Dang Y, Liu X, Ren J, Wang H. Exogenous brain‑derived neurotrophic factor attenuates neuronal apoptosis and neurological deficits after subarachnoid hemorrhage in rats. Experimental and Therapeutic Medicine 2019;18(5):3837-44.
  • 17. Demedts IK, Demoor T, Bracke KR, Joos GF, Brusselle GG. Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. Respiratory Research 2006;7:1-10.
  • 18. Suresh MV, Yalamanchili G, Rao TC, Aktay S, Kralovich A, Shah YM, Raghavendran K. Hypoxia‐inducible factor (HIF)‐1α‐induced regulation of lung injury in pulmonary aspiration is mediated through NF‐kB. FASEB BioAdvances 2022;4(5):309.
  • 19. Sargon MF. Lungs and hypoxia: a review of the literature. Anatomy 2021;15(1):76-83.
  • 20. Pereira M, Liang J, Edwards-Hicks J, Meadows AM, Hinz C, Liggi S, et al. Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting. Cell Reports 2024;43(2).
  • 21. Galea J, Ogungbenro K, Hulme S, Patel H, Scarth S, Hoadley M, et al. Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study. Journal of Neurosurgery 2017;128(2):515-23.
  • 22. Hvas C, Nørregaard R, Nielsen T, Barklin A, Tønnesen E. Brain death increases COX‐1 and COX‐2 expression in the renal medulla in a pig model. Acta Anaesthesiologica Scandinavica 2014;58(2):243-50.
  • 23. Priante G, Gianesello L, Ceol M, Del Prete D, Anglani F. Cell death in the kidney. International Journal of Molecular Sciences 2019;20(14):3598.
  • 24. Ratliff BB, Abdulmahdi W, Pawar R, Wolin MS. Oxidant mechanisms in renal injury and disease. Antioxidants & Redox Signaling 2016;25(3):119-46.
There are 24 citations in total.

Details

Primary Language English
Subjects Brain and Nerve Surgery (Neurosurgery)
Journal Section Research Articles
Authors

Ali Serdar Oğuzoğlu 0000-0002-1735-4062

Halil Aşçı 0000-0002-1545-035X

Musa Canan 0009-0005-7279-0026

Nilgün Şenol 0000-0002-1714-3150

Özlem Özmen 0000-0002-1835-1082

Project Number TSG-2022-8783
Publication Date December 26, 2024
Submission Date May 20, 2024
Acceptance Date September 19, 2024
Published in Issue Year 2024 Volume: 31 Issue: 4

Cite

Vancouver Oğuzoğlu AS, Aşçı H, Canan M, Şenol N, Özmen Ö. Inflammation and Apoptosis-Related Damage in Lung, Liver, and Kidney Tissues due to Subarachnoidal Hemorrhage. Med J SDU. 2024;31(4):310-7.

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