Skip to main content

Advertisement

SpringerLink
Log in

Effect of osmotherapy with hypertonic saline on regional cerebral edema following experimental stroke: a study utilizing magnetic resonance imaging

  • Original Paper
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Introduction

Hypertonic saline (HS) solutions are increasingly being utilized as osmotherapeutic agents for the treatment of cerebral edema associated with brain injury from diverse etiologies.

Methods

In a rat model of permanent focal ischemia, we (1) determined the effect of HS therapy on regional brain water content with T1- and T2-weighted magnetic resonance imaging (MRI) and (2) tested the hypothesis that HS therapy modulates the expression of aquaporin-4 (AQP4) in the ischemic brain.

Results

Halothane-anesthetized male Wistar rats were subjected to permanent middle cerebral artery occlusion (MCAO) and at 6 hr post-MCAO were treated with either continuous intravenous infusion of 0.9% saline (NS) or 7.5% HS for 18 hr. While lesion size measured on T2-weighted imaging did not differ between NS (580 ± 217 mm3; mean ± SD) and HS (460 ± 86 mm3) treatments, there was a correlation between T2 values and tissue water content as determined by wet-to-dry ratio in the caudoputamen (CP) complex of ischemic core (r = 0.612, P < 0.05). There were significant differences in T1 values with treatment in the ischemic cortex (NS: 2.08 ± 0.13; HS: 1.78 ± 0.20) and CP complex (NS: 2.09 ± 0.14; HS: 1.77 ± 0.22), but there was no correlation between T2 values and regional brain tissue water content in the peri-infarct regions and the non-ischemic hemisphere. There were significant differences in AQP4 protein expression in the ischemic hemisphere between NS and HS-treated rats.

Conclusions

These data demonstrate that (1) T2-weighted MRI imaging correlates with tissue water content in the ischemic core but not in the peri-infarct regions, and (2) attenuation of ischemia-evoked cerebral edema involves the modulation of AQP4 channels in the brain.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Berrouschot J, Sterker M, Bettin S et al. Mortality of space-occupying (‘malignant’) middle cerebral artery infarction under conservative intensive care. Intensive Care Med 1998;24:620–3

    Article  PubMed  CAS  Google Scholar 

  2. Hacke W, Schwab S, Horn M et al. “Malignant” middle cerebral artery infarction: clinical course and prognostic signs. Arch Neurol 1996;53:309–15

    PubMed  CAS  Google Scholar 

  3. Bhardwaj A, Ulatowski JA. Hypertonic saline solutions in acute brain injury. Current Opin Crit Care 2004;10:126–31

    Article  Google Scholar 

  4. Harukuni I, Kirsch JR, Bhardwaj A. Osmotherapy in acute brain resuscitation. J Anesth 2002;16:229–37

    Article  PubMed  Google Scholar 

  5. Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema, intracranial hypertension. Crit Care Med 2000;28:3301–13

    Article  PubMed  CAS  Google Scholar 

  6. Paczynski RP. Osmotherapy. Basic concepts and controversies. Crit Care Clin 1997;13:105–29

    Article  PubMed  CAS  Google Scholar 

  7. Schell RM, Applegate II RL, Cole DJ. Salt, starch, and water on the brain. J Neurosurg Anesth 1996;8:178–82

    CAS  Google Scholar 

  8. Zornow MH. Hypertonic saline as a safe and efficacious treatment of intracranial hypertension. J Neurosurg Anesth 1996;8:175–7

    CAS  Google Scholar 

  9. Chen CH, Toung TJ, Sapirstein A et al. Effect of duration of osmotherapy on blood–brain barrier disruption and regional cerebral edema after experimental stroke. J Cereb Blood Flow and Metab 2006;26:951–8

    Article  CAS  Google Scholar 

  10. Toung TJK, Hurn PD, Traystman RJ et al. Global brain water increases after experimental focal cerebral ischemia: Effect of hypertonic saline. Crit Care Med 2002;30:644–9

    Article  PubMed  Google Scholar 

  11. Toung TJ, Chang Y, Lin J et al. Increases in lung and brain water following experimental stroke: effect of mannitol and hypertonic saline. Crit Care Med 2005;33:203–8

    Article  PubMed  CAS  Google Scholar 

  12. Prough DS, Whitley J, Taylor CL et al. Regional cerebral blood flow following resuscitation from hemorrhagic shock with hypertonic saline. Influence of a subdural mass. Anesthesiology 1991;75:319–27

    CAS  Google Scholar 

  13. Badaut J, Lasbennes F, Magistretti PJ et al. Aquaporins in brain: distribution, physiology, and pathophysiology. J Cereb Blood Flow Metab 2002;22:367–78

    Article  PubMed  CAS  Google Scholar 

  14. King LS, Agre P. Pathophysiology of the aquaporin water channels. Annu Rev Physiol 1996;58:619–48

    Article  PubMed  CAS  Google Scholar 

  15. Manley GT, Fujimura M, Ma T 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 

  16. Amiry-Moghaddam M, Otsuka T, Hurn PD et al. An α-syntrophin dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain. Proc Natl Acad Sci USA 2003;100:2106–11

    Article  PubMed  CAS  Google Scholar 

  17. Arima H, Yamamoto N, Sobue K 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;7;278:44525–34

    Article  CAS  Google Scholar 

  18. de Castro Ribeiro M, Hirt L, Bogousslavsky J et al. Time course of aquaporin expression after transient focal cerebral ischemia in mice. J Neurosci Res 2006;83:1231–40

    Article  CAS  Google Scholar 

  19. Bacher A, Wei J, Grafe MR et al. Serial determinations of cerebral water content by magnetic resonance imaging after an infusion of hypertonic saline. Crit Care Med 1998;26:108–14

    Article  PubMed  CAS  Google Scholar 

  20. Barber PA, Hoyte I, Kirk D et al. Early T1 and T2-weighted MRI signatures of transient and permanent middle cerebral artery occlusion in a murine stroke model studied at 9.4T. Neurosci Lett 2005;388:54–9

    Article  PubMed  CAS  Google Scholar 

  21. Barbier EL, Liu L, Grillon L et al. Focal brain ischemia in rat: acute changes in brain tissue T1 reflect acute increase in brain tissue water content. NMR Biomed 2005;18:499–506

    Article  PubMed  Google Scholar 

  22. Loubbinoux I, Volk A, Borredon J et al. Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging. Stroke 1997;28:419–26

    Google Scholar 

  23. Shigeno T, Brock M, Shigeno S et al. The determination of brain water content: microgravimetry versus drying-weighing method. J Neurosurg 1982;57:99–107

    Article  PubMed  CAS  Google Scholar 

  24. Alkayed NJ, Harukuni I, Kimes AS et al. Gender-linked brain injury in experimental stroke. Stroke 1998;29:159–65

    PubMed  CAS  Google Scholar 

  25. Longa EZ, Weinstein PR, Carlson S et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989;20:84–91.

    PubMed  CAS  Google Scholar 

  26. Goto S, Xue R, Sugo N et al. Poly(ADP-ribose) polymerase impairs early and long-term experimental stroke recovery. Stroke 2002;3:1101–6

    Article  Google Scholar 

  27. Lin TN, He YY, Wu G et al. Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke 1993;24:117–21

    PubMed  CAS  Google Scholar 

  28. Nielsen S, Nagelhus EA, Amiri-Moghaddam M et al. Specialized membrane domains for water transport in glial cells: High resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 1997;17:171–180

    PubMed  CAS  Google Scholar 

  29. Weed LH, McKibben PS. Experimental alteration of brain bulk. Am J Physiol 1919; 48:531–55

    Google Scholar 

  30. Velasco IT, Pontieri V, Rocha e Silva M Jr et al. Hyperosmotic NaCl and severe hemorrhagic shock. Am J Physiol 1980;239:H664–73

    PubMed  CAS  Google Scholar 

  31. Rocha-e-Silva M, Poli de Figueiredo LF. Small volume hypertonic resuscitation of circulatory shock. Clinics 2005;60:159–72

    PubMed  Google Scholar 

  32. Arbabi S, Garcia I, Bauer G et al. Hypertonic saline induces prostacyclin production via extracellular signal-regulated kinase (ERK) activation. J Surg Res 1999;83:141–6

    Article  PubMed  CAS  Google Scholar 

  33. Neumann-Haeflin T, Kastrup A, de Crespigny A et al. Serial MRI after transient focal cerebral ischemia in rats: dynamics of tissue injury, blood-brain barrier damage, and edema formation. Stroke 2000;31: 1965–72

    Google Scholar 

  34. Chang Y, Chen TY, Chen CH et al. Plasma arginine-vasopressin following experimental stroke: effect of osmotherapy. J Appl Physiol 2006;100:1445–51

    Article  PubMed  CAS  Google Scholar 

  35. Cascino T, Baglivo J, Conti J et al. Quantitative CT assessment of furosemide- and mannitol-induced changes in brain water content. Neurology 1983;33:898–903

    PubMed  CAS  Google Scholar 

  36. Abe O, Okubo T, Hayashi N et al. Temporal changes of apparent diffusion coefficients of water and metabolites in rats with hemispheric infarction; experimental study of transhemispheric diaschisis in the contralateral hemisphere at 7 tesla. J Cereb Blood Flow Metab 2000;20:726–35

    Article  PubMed  CAS  Google Scholar 

  37. Abbott NJ. Inflammatory mediators and modulation of blood-brain barrier permeability. Cell Mol Neurobiol 2000;20:131–47

    Article  PubMed  CAS  Google Scholar 

  38. Bemana I, Nagao S. Treatment of brain edema with nonpeptide arginine vasopressin V1 receptor antagonist OPC-21268 in rats. Neurosurgery 1999;44:148–54

    Article  PubMed  CAS  Google Scholar 

  39. van Bruggen N, Thibodeaux H, Palmer JT et al. VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion in mouse brain. J Clin Invest 1999;104: 1613–20.

    Article  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  41. Amiry-Moghaddam M, Xue R, Haug FM et al. Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia. FASEB J 2004;18:542–44

    PubMed  CAS  Google Scholar 

  42. Vajda Z, Promeneur D, Doczi T et al. Increased aquaporin-4 immunoreactivity in rat brain in response to systemic hyponatremia. Biochem Biophys Res Commun 2000;270:495–503

    Article  PubMed  CAS  Google Scholar 

  43. Frydenlund DS, Bhardwaj A, Otsuka T et al. Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice. Proc Natl Acad Sci USA 2006;103:13532–6

    Article  PubMed  CAS  Google Scholar 

  44. Quick AM, Cipolla MJ. Pregnancy-induced up-regulation of aquaporin-4 protein in brain and its role in eclampsia. FASEB J 2005;19:170–5

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Public Health Service NIH grant NS046379

Author information

Author notes

  1. Anish Bhardwaj

    Present address: Departments of Neurology, Neurological Surgery and Anesthesiology/Peri-Operative Medicine, Oregon Health and Science University, Mackenzie Hall, Room 2204, 3181 SW Sam Jackson Park Road, L-226, Portland, OR, 97239-3098, USA

Authors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MA, USA

    Chih-Hung Chen, Xiaoling Li & Anish Bhardwaj

  2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Anish Bhardwaj

  3. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Rong Xue, Jiangyang Zhang & Susumu Mori

  4. Department of Neurology and Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Chih-Hung Chen

Authors
  1. Chih-Hung Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rong Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiangyang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoling Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Susumu Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anish Bhardwaj
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anish Bhardwaj.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, CH., Xue, R., Zhang, J. et al. Effect of osmotherapy with hypertonic saline on regional cerebral edema following experimental stroke: a study utilizing magnetic resonance imaging. Neurocrit Care 7, 92–100 (2007). https://doi.org/10.1007/s12028-007-0033-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-007-0033-9

Keywords

Search

Navigation