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Temporal profiles of aquaporin 4 expression and astrocyte response in the process of brain damage in fat embolism model in rats

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Abstract

Purpose

Fat embolism syndrome is a serious complication observed after trauma, orthopedic surgery, and cardiac surgery. We investigated brain damage in relationship to temporal profiles of water channel aquaporin 4 (AQP4) and astrocyte response to fat embolism in rats.

Methods

Triolein (2 μl) was injected into the right internal carotid artery in rats. Neurological outcome (score: range, 0–5 = no deficit–dead), brain water content, histopathology, and immunohistochemistry for AQP4 and glial fibrillary acidic protein (GFAP) were evaluated at 2 h (2 h group, n = 12), 24 h (24 h group, n = 12), and 72 h (72 h group, n = 12) after triolein injection. Saline was injected in the control (C) group (n = 12).

Results

Neurological deficit score (median score of 2) and brain water content (mean value, 86.2%) increased significantly at 2 h with no progressive increase over 72 h. Damaged tissues with shrunken and triangular-shaped neurons with vacuole degeneration in cytoplasm and halo formation were distributed mainly, but not exclusively, to the ipsilateral hemisphere and were associated with increase in infiltration of inflammatory cells during the time course. Increases in immunostaining for AQP4 and GFAP were observed in the peri-affected region but not in the core. Reactive astrocytes with hypertrophy and dendrite elongation were detected at 72 h in the peri-affected region.

Conclusion

The results suggest that brain damage with edema is induced very rapidly after triolein injection in association with increase in AQP4 expression and GFAP in the peri-affected region.

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References

  1. Johnson MJ, Lucas GL. Fat embolism syndrome. Orthopedics. 1996;19:41–9.

    PubMed  CAS  Google Scholar 

  2. Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat embolism syndrome. A 10-year review. Arch Surg. 1997;132:435–9.

    PubMed  CAS  Google Scholar 

  3. Meeke RI, Fitzpatrick GJ, Phelan DM. Cerebral oedema and the fat embolism syndrome. Intensive Care Med. 1987;13:291–2.

    Article  PubMed  CAS  Google Scholar 

  4. di Summa A, Beltramello A, Fratucello GB, Bongiovanni LG, Zanette G, Polo A. Cerebral fat embolism: debated acute posttraumatic encephalography. Eur Neurol. 1998;40:55–6.

    PubMed  CAS  Google Scholar 

  5. Prentiss JE, Imoto EM. Fat embolism, ARDS, coma, death: the four horsemen of the fractured hip. Hawaii Med J. 2001;60:15–9.

    PubMed  CAS  Google Scholar 

  6. Kariya N, Shindoh M, Hayashi Y, Nakasuji M, Nishi S, Nishikawa K, et al. A case of fatal paradoxical fat embolism syndrome detected by intraoperative transesophageal echocardiography. Anesth Analg. 2001;92:688–9.

    Article  PubMed  CAS  Google Scholar 

  7. Ghatak NR, Sinnenberg RJ, deBlois GG. Cerebral fat embolism following cardiac surgery. Stroke. 1983;14:619–21.

    PubMed  CAS  Google Scholar 

  8. Brown WR, Moody DM, Challa VR. Cerebral fat embolism from cardiopulmonary bypass. J Neuropathol Exp Neurol. 1999;58:109–19.

    Article  PubMed  CAS  Google Scholar 

  9. Hammon JW, Stump DA, Butterworth JB, Moody DM. Approaches to reduce neurologic complications during cardiac surgery. Semin Thorac Cardiovasc Surg. 2001;13:184–91.

    Article  PubMed  CAS  Google Scholar 

  10. Drew PA, Smith E, Thomas PD. Fat distribution and changes in the blood–brain barrier in a rat model of cerebral arterial fat embolism. J Neurol Sci. 1998;156:138–43.

    Article  PubMed  CAS  Google Scholar 

  11. Kim HJ, Lee CH, Lee SH, Cho BM, Kim HK, Park BR, et al. Early development of vasogenic edema in experimental cerebral fat embolism in cats: correlation with MRI and electron microscopic findings. Invest Radiol. 2001;36:460–9.

    Article  PubMed  CAS  Google Scholar 

  12. Kim HJ, Lee JH, Lee CH, Lee SH, Moon TY, Cho BM, et al. Experimental cerebral fat embolism: embolic effects of triolein and oleic acid depicted by MR imaging and electron microscopy. Am J Neuroradiol. 2002;23:1516–23.

    PubMed  Google Scholar 

  13. Kim HJ, Lee CH, Lee SH, Moon TY. Magnetic resonance imaging and histologic findings of experimental cerebral fat embolism. Invest Radiol. 2003;38:625–34.

    Article  PubMed  Google Scholar 

  14. Kim YW, Kim HJ, Cho BM, Moon TY, Eun CK. The study of cerebral hemodynamics in the hyperacute stage of fat embolism induced by triolein emulsion. Am J Neuroradiol. 2006;27:398–401.

    PubMed  CAS  Google Scholar 

  15. Yamamoto N, Yoneda K, Asai K, Sobue K, Tada T, Fujita Y, et al. Alterations in the expression of the AQP family in cultured rat astrocytes during hypoxia and reoxygenation. Brain Res Mol Brain Res. 2001;90:26–38.

    Article  PubMed  CAS  Google Scholar 

  16. Arima H, Yamamoto N, Sobue K, Umenishi F, Tada T, Katsuya H, et al. Hyperosmolar mannitol simulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes. J Biol Chem. 2003;278:44525–34.

    Article  PubMed  CAS  Google Scholar 

  17. Vizuete ML, Venero JL, Vargas C, Ilundain AA, Echevarria M, Machado A, et al. Differential upregulation of aquaporin-4 mRNA expression in reactive astrocytes after brain injury: potential role in brain edema. Neurobiol Dis. 1999;6:245–58.

    Article  PubMed  CAS  Google Scholar 

  18. Taniguchi M, Yamashita T, Kumura E, Tamatani M, Kobayashi A, Yokawa T, et al. Induction of aquaporin-4 water channel mRNA after focal cerebral ischemia in rat. Brain Res Mol Brain Res. 2000;78:131–7.

    Article  PubMed  CAS  Google Scholar 

  19. Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med. 2000;6:159–63.

    Article  PubMed  CAS  Google Scholar 

  20. Ke C, Poon WS, Ng HK, Pang JC, Chan Y. Heterogeneous responses of aquaporin-4 in oedema formation in a replicated severe traumatic brain injury model in rats. Neurosci Lett. 2001;301:21–4.

    Article  PubMed  CAS  Google Scholar 

  21. Papadopoulos MC, Manley GT, Krishna S, Verkman AS. Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J. 2004;18:1291–3.

    PubMed  CAS  Google Scholar 

  22. Papadopoulos MC, Verkman AS. Aquaporin-4 gene disruption in mice reduces brain swelling and mortality in pneumococcal meningitis. J Biol Chem. 2005;280:13906–12.

    Article  PubMed  CAS  Google Scholar 

  23. Mao X, Enno TL, Del Bigio MR. Aquaporin 4 changes in rat brain with severe hydrocephalus. Eur J Neurosci. 2006;23:2929–36.

    Article  PubMed  Google Scholar 

  24. Djelouah I, Lefevre G, Ozier Y, Rosencher N, Tallet F. Fat embolism in orthopedic surgery: role of bone marrow fatty acid. Anesth Analg. 1997;85:441–3.

    Article  PubMed  CAS  Google Scholar 

  25. Insull W Jr, Bartsch GE. Fatty acid composition of human adipose tissue related to age, sex, and race. Am J Clin Nutr. 1967;20:13–23.

    PubMed  Google Scholar 

  26. Xiong L, Zheng Y, Wu M, Hou L, Zhu Z, Zhang X, et al. Preconditioning with isoflurane produces dose-dependent neuroprotection via activation of adenosine triphosphate-regulated potassium channels after focal cerebral ischemia in rats. Anesth Analg. 2003;96:233–7.

    Article  PubMed  CAS  Google Scholar 

  27. Matsumoto S, Matsumoto M, Yamashita A, Ohtake K, Ishida K, Morimoto Y, et al. The temporal profile of the reaction of microglia, astrocytes, and macrophages in the delayed onset paraplegia after transient spinal cord ischemia in rabbits. Anesth Analg. 2003;96:1777–84.

    Article  PubMed  Google Scholar 

  28. Halsey JH Jr, Conger KA, Garcia JH, Sarvary E. The contribution of reoxygenation to ischemic brain damage. J Cereb Blood Flow Metab. 1991;11:994–1000.

    PubMed  CAS  Google Scholar 

  29. Petito CK, Morgello S, Felix JC, Lesser ML. The two patterns of reactive astrocytosis in postischemic rat brain. J Cereb Blood Flow Metab. 1990;10:850–9.

    PubMed  CAS  Google Scholar 

  30. Li Y, Chopp M, Zhang ZG, Zhang RL. Expression of glial fibrillary acidic protein in areas of focal cerebral ischemia accompanies neuronal expression of 72-kDa heat shock protein. J Neurol Sci. 1995;128:134–42.

    Article  PubMed  CAS  Google Scholar 

  31. Yamashita K, Vogel P, Fritze K, Back T, Hossmann KA, Wiessner C. Monitoring the temporal and spatial activation pattern of astrocytes in focal cerebral ischemia using in situ hybridization to GFAP mRNA: comparison with sgp-2 and hsp70 mRNA and the effect of glutamate receptor antagonists. Brain Res. 1996;735:285–97.

    Article  PubMed  CAS  Google Scholar 

  32. Schwartz JP, Nishiyama N. Neurotrophic factor gene expression in astrocytes during development and following injury. Brain Res Bull. 1994;35:403–7.

    Article  PubMed  CAS  Google Scholar 

  33. Kakinuma Y, Hama H, Sugiyama F, Yagami K, Goto K, Murakami K, et al. Impaired blood–brain barrier function in angiotensinogen-deficient mice. Nat Med. 1998;4:1078–80.

    Article  PubMed  CAS  Google Scholar 

  34. Nawashiro H, Brenner M, Fukui S, Shima K, Hallenbeck JM. High susceptibility to cerebral ischemia in GFAP-null mice. J Cereb Blood Flow Metab. 2000;20:1040–4.

    Article  PubMed  CAS  Google Scholar 

  35. Saadoun S, Papadopoulos MC, Watanabe H, Yan D, Manley GT, Verkman AS. Involvement of aquaporin-4 in astroglial cell migration and glial scar formation. J Cell Sci. 2005;118:5691–8.

    Article  PubMed  CAS  Google Scholar 

  36. Matsui T, Mori T, Tateishi N, Kagamiishi Y, Satoh S, Katsube N, et al. Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part I: enhanced astrocytic synthesis of s-100β in the periinfarct area precedes delayed infarct expansion. J Cereb Blood Flow Metab. 2002;22:711–22.

    Article  PubMed  CAS  Google Scholar 

  37. Tateishi N, Mori T, Kagamiishi Y, Satoh S, Katsube N, Morikawa E, et al. Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part II: suppression of astrocytic activation by a novel agent (R)-(–)-2-propyloctanoic acid (ONO-2506) leads to mitigation of delayed infarct expansion and early improvement of neurologic deficits. J Cereb Blood Flow Metab. 2002;22:723–34.

    Article  PubMed  CAS  Google Scholar 

  38. Ribeiro Mde C, Hirt L, Bogousslavsky J, Regli L, Badaut J. Time course of aquaporin expression after transient focal cerebral ischemia in mice. J Neurosci Res. 2006;83:1231–40.

    Article  PubMed  CAS  Google Scholar 

  39. Kaur C, Sivakumar V, Zhang Y, Ling EA. Hypoxia-induced astrocytic reaction and increased vascular permeability in the rat cerebellum. Glia. 2006;54:826–39.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported in part by a grant-in-aid for scientific research (grant no. 12671474), the Japanese Ministry of Education, Culture, Sports and Technology.

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Authors and Affiliations

  1. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Toru Gohara, Kazuyoshi Ishida, Kazuhiko Nakakimura, Mitsuyoshi Yoshida, Shiro Fukuda, Mishiya Matsumoto & Takefumi Sakabe

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  1. Toru Gohara
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  2. Kazuyoshi Ishida
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  3. Kazuhiko Nakakimura
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  4. Mitsuyoshi Yoshida
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  7. Takefumi Sakabe
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Correspondence to Kazuyoshi Ishida.

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Gohara, T., Ishida, K., Nakakimura, K. et al. Temporal profiles of aquaporin 4 expression and astrocyte response in the process of brain damage in fat embolism model in rats. J Anesth 24, 225–233 (2010). https://doi.org/10.1007/s00540-009-0831-7

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  • DOI: https://doi.org/10.1007/s00540-009-0831-7

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