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Mild Traumatic Brain Injury and Subsequent Acute Pulmonary Inflammatory Response

  • Lim, Seung Hyuk (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Jung, Harry (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Youn, Dong Hyuk (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Kim, Tae Yeon (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Han, Sung Woo (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Kim, Bong Jun (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Lee, Jae Jun (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Jeon, Jin Pyeong (Department of Neurosurgery, Hallym University College of Medicine)
  • Received : 2021.12.17
  • Accepted : 2022.02.21
  • Published : 2022.09.01

Abstract

Objective : The influence of moderate-to-severe traumatic brain injury (TBI) on acute pulmonary injury is well established, but the association between acute pulmonary injury and mild TBI has not been well studied. Here, we evaluated the histological changes and fluctuations in inflammatory markers in the lungs to determine whether an acute pulmonary inflammatory response occurred after mild TBI. Methods : Mouse models of mild TBI (n=24) were induced via open-head injuries using a stereotaxic impactor. The brain and lungs were examined 6, 24, and 72 hours after injury and compared to sham-operated controls (n=24). Fluoro-Jade B staining and Astra blue and hematoxylin staining were performed to assess cerebral neuronal degeneration and pulmonary histological architecture. Quantitative real-time polymerase chain reaction analysis was done to measure inflammatory cytokines. Results : Increased neuronal degeneration and the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β were observed after mild TBI. The IL-6, TNF-α, and TGF-β levels in mice with mild TBI were significantly different compared to those of sham-operated mice 24 hours after injury, and this was more pronounced at 72 hours. Mild TBI induced acute pulmonary interstitial edema with cell infiltration and alveolar morphological changes. In particular, a significant infiltration of mast cells was observed. Among the inflammatory cytokines, TNF-α was significantly increased in the lungs at 6 hours, but there was no significant difference 24 and 72 hours after injury. Conclusion : Mild TBI induced acute pulmonary interstitial inflammation and alveolar structural changes, which are likely to worsen the patient's prognosis.

Keywords

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HR21C0198) and Hallym Research Fund.

References

  1. Austin V, Ku JM, Miller AA, Vlahos R : Ischaemic stroke in mice induces lung inflammation but not acute lung injury. Sci Rep 9 : 3622, 2019
  2. Bae YH, Joo H, Bae J, Hyeon SJ, Her S, Ko E, et al. : Brain injury induces HIF-1α-dependent transcriptional activation of LRRK2 that exacerbates brain damage. Cell Death Dis 9 : 1125, 2018
  3. Beller E, Reuter L, Kluge A, Preibisch C, Lindauer U, Bogdanov A, et al. : Pilot study to assess visualization and therapy of inflammatory mechanisms after vessel reopening in a mouse stroke model. Sci Rep 8 : 745, 2018
  4. Brambrink AM, Dick WF : Neurogenic pulmonary edema. pathogenesis, clinical picture and therapy. Anaesthesist 46 : 953-963, 1997 https://doi.org/10.1007/s001010050492
  5. Cai C, Cao Z, Loughran PA, Kim S, Darwiche S, Korff S, et al. : Mast cells play a critical role in the systemic inflammatory response and end-organ injury resulting from trauma. J Am Coll Surg 213 : 604-615, 2011 https://doi.org/10.1016/j.jamcollsurg.2011.08.009
  6. Englert JA, Macias AA, Amador-Munoz D, Pinilla Vera M, Isabelle C, Guan J, et al. : Isoflurane ameliorates acute lung injury by preserving epithelial tight junction integrity. Anesthesiology 123 : 377-388, 2015 https://doi.org/10.1097/ALN.0000000000000742
  7. Graziottin A, Skaper SD, Fusco M : Mast cells in chronic inflammation, pelvic pain and depression in women. Gynecol Endocrinol 30 : 472-477, 2014 https://doi.org/10.3109/09513590.2014.911280
  8. Humphries DC, O'Neill S, Scholefield E, Dorward DA, Mackinnon AC, Rossi AG, et al. : Cerebral concussion primes the lungs for subsequent neutrophil-mediated injury. Crit Care Med 46 : e937-e944, 2018 https://doi.org/10.1097/CCM.0000000000003270
  9. Kempuraj D, Selvakumar GP, Thangavel R, Ahmed ME, Zaheer S, Raikwar SP, et al. : Mast cell activation in brain injury, stress, and posttraumatic stress disorder and alzheimer's disease pathogenesis. Front Neurosci 11 : 703, 2017
  10. Kerr NA, De Rivero Vaccari JP, Abbassi S, Kaur H, Zambrano R, Wu S, et al. : Traumatic brain injury-induced acute lung injury: evidence for activation and inhibition of a neural-respiratory-inflammasome axis. J Neurotrauma 35 : 2067-2076, 2018 https://doi.org/10.1089/neu.2017.5430
  11. Lefevre-Dognin C, Cogne M, Perdrieau V, Granger A, Heslot C, Azouvi P : Definition and epidemiology of mild traumatic brain injury. Neurochirurgie 67 : 218-221, 2021 https://doi.org/10.1016/j.neuchi.2020.02.002
  12. Malaviya R, Ikeda T, Ross E, Abraham SN : Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature 381 : 77-80, 1996 https://doi.org/10.1038/381077a0
  13. Nicolls MR, Laubach VE : Traumatic brain injury: lungs in a RAGE. Sci Transl Med 6 : 252fs234, 2014
  14. Prince JM, Levy RM, Yang R, Mollen KP, Fink MP, Vodovotz Y, et al. : Toll-like receptor-4 signaling mediates hepatic injury and systemic inflammation in hemorrhagic shock. J Am Coll Surg 202 : 407-417, 2006 https://doi.org/10.1016/j.jamcollsurg.2005.11.021
  15. Rincon F, Ghosh S, Dey S, Maltenfort M, Vibbert M, Urtecho J, et al. : Impact of acute lung injury and acute respiratory distress syndrome after traumatic brain injury in the united States. Neurosurgery 71 : 795-803, 2012 https://doi.org/10.1227/NEU.0b013e3182672ae5
  16. Rouze A, Jaillette E, Nseir S : Relationship between microaspiration of gastric contents and ventilator-associated pneumonia. Ann Transl Med 6 : 428, 2018
  17. Vaickus M, Hsieh T, Kintsurashvili E, Kim J, Kirsch D, Kasotakis G, et al. : Mild traumatic brain injury in mice beneficially alters lung NK1R and structural protein expression to enhance survival after pseudomonas aeruginosa infection. Am J Pathol 189 : 295-307, 2019 https://doi.org/10.1016/j.ajpath.2018.10.019
  18. Weber DJ, Gracon AS, Ripsch MS, Fisher AJ, Cheon BM, Pandya PH, et al. : The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation. Sci Transl Med 6 : 252ra124, 2014
  19. Youn DH, Tran NM, Kim BJ, Kim Y, Jeon JP, Yoo H : Shape effect of cerium oxide nanoparticles on mild traumatic brain injury. Sci Rep 11 : 15571, 2021
  20. Zhang J, Teng Z, Song Y, Hu M, Chen C : Inhibition of monoacylglycerol lipase prevents chronic traumatic encephalopathy-like neuropathology in a mouse model of repetitive mild closed head injury. J Cereb Blood Flow Metab 35 : 443-453, 2015 https://doi.org/10.1038/jcbfm.2014.216