Skip to main content

Age-dependent MRI-detected lesions at early stages of transient global ischemia in rat brain

Magnetic Resonance Materials in Physics, Biology and Medicine volume 17, pages 109–116 (2004)Cite this article

Abstract

Although ischemic stroke has higher incidence and severity in aged than in young humans, the age factor is generally neglected in ischemia animal models. This study was aimed at comparing age-dependent effects at early stages of transient global cerebral ischemia (TGCI) in rats. TGCI was induced in two groups of rats (3–6 and 20–24 months old, respectively) by exposure to 15% oxygen and 15 min occlusion of the two common carotid arteries. Brains were analysed in vivo by MRI–apparent diffusion coefficient (ADC) and T2 maps–at 1–3 h post-TGCI and in vitro by histochemical examination of triphenyltetrazolium chloride (TTC)-stained slices. At 1–3 h post-TGCI, a higher incidence of lesions was found in aged than in young rats especially in the hippocampus and cortex (occipital plus parietal) but not in the thalamus. The lesioned regions showed lower ADC values in aged than in younger rats. The most substantial ADC decreases were associated with enhanced spin-spin relaxation and lower TTC staining. The different responses of the two age groups support the use of aged animals for investigations on different ischemia models. Our model of brain ischemia appears appropriate for further studies including drug effects.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Rothwell PM, Coull AJ, Giles MF, Howard SC, Silver LE, Bull LM, Gutnikov SA, Edwards P, Mant D, Sackley CM, Farmer A, Sandercock PAG, Dennis MS, Warlow CP, Bamford JM, Anslow P (2004) Change in stroke incidence, mortality, case-fatality, severity and risk-factors in Oxfordshire, UK from 1981 to 2004 (Oxford vascular study). Lancet 363:1925–1933

    Google Scholar 

  2. Thorvaldsen P, Davidsen M, Brønnum-Hansen H, Schroll M (1999) Stable stroke occurrence despite incidence reduction in an aging population. Stroke trends in the Danish monitoring trends and determinants in cardiovascular disease (MONICA) population. Stroke 30:2529–2534

    Google Scholar 

  3. Giampaoli S, Menotti A, Righetti G, Verdecchia A (1990) Sorveglianza degli eventi coronarici. L’esperienza e gli insegnamenti dell’Area Latina del progetto MONICA . G Ital Cardiol 20:267–271

    Google Scholar 

  4. Millikan C (1992) Animal stroke models. Stroke 23:795–797

    Google Scholar 

  5. Pulsinelli WA (1995) The therapeutic window in ischemic brain injury. Curr Opin Neurol 8:3–5

    Google Scholar 

  6. Michalek H, Fortuna S, Pintor A (1989) Age-related differences in brain choline acetyltranferase, cholinesterases and muscarinic receptor sites in two strains of rats. Neurobiol Aging 10:143–149

    Google Scholar 

  7. Pintor A, Fortuna S, Michalek H (1994) Carbachol-induced accumulation of inositol phosphates and its modulation by excitatory amino acids in cortical slices of young and aged rats with down-regulation of muscarinic M-1 receptors. Neurochem Res 19:1311–1317

    Google Scholar 

  8. Cunha RA, Almeida T, Ribeiro JA (2001) Parallel modification of adenosine extracellular metabolism and modulatory action in the hippocampus of aged rats. J Neurochem 76:372–382

    Google Scholar 

  9. Schaefer PW, Grant PE, Gonzalez RG (2000) Diffusion-weighted MR imaging of the brain. Radiology 217:331–345

    CAS  PubMed  Google Scholar 

  10. Hoehn M, Nicolay K, Franke C, van der Sanden B (2001) Application of magnetic resonance to animal models of cerebral ischemia. J Magn Reson Imaging 14:491–509

    Article  CAS  PubMed  Google Scholar 

  11. Schaefer PW (2001) Applications of DWI in clinical neurology. J Neurol Sci 186:S25–S35

    Google Scholar 

  12. Mintorovitch J, Yang GY, Shimizu H, Kucharczyk J, Chan PH, Weinstein PR (1994) Diffusion-weighted magnetic resonance imaging of acute focal cerebral ischemia: comparison of signal intensity with changes in brain water and Na+/K+ ATPase activity. J Cereb Blood Flow Metab 14:332–336

    Google Scholar 

  13. Benveniste H, Hedlund LW, Johnson GA (1992) Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted magnetic resonance microscopy. Stroke 23:746–754

    Google Scholar 

  14. Qiao M, Malisza KL, Del Bigio MR, Tuor UI (2002) Transient hypoxia-ischemia in rats: changes in diffusion-sensitive MR imaging findings, extracellular space, and Na+-K+-adenosine triphosphatase and cytochrome oxidase activity. Radiology 223:65–75

    CAS  PubMed  Google Scholar 

  15. Sykova E, Svoboda J, Polak J, Chvatal A (1994) Extracellular volume fraction and diffusion characteristics during progressive ischemia and terminal anoxia in the spinal cord of the rat. J Cereb Blood Flow Metab 14:301–311

    Google Scholar 

  16. Wick M, Nagatomo Y, Prielmeier F, Frahm J (1995) Alteration of intracellular metabolite diffusion in rat brain in vivo during ischemia and reperfusion. Stroke 26:1930–1934

    Google Scholar 

  17. van der Toorn A, Dijkhuizen R, Tulleken C, Nicolay K (1996) Diffusion of metabolites in normal and ischemic rat brain measured by localised 1H MRS . Magn Reson Med 36:914–922

    Google Scholar 

  18. Duong TQ, Ackerman JJ, Ying HS, Neil JJ (1998) Evaluation of extra- and intracellular apparent diffusion in normal and globally ischemic rat brain via 19F NMR . Magn Reson Med 40:1–13

    Google Scholar 

  19. Aden U, Dahlberg V, Fredholm BB, Lai LJ, Chen Z, Bjelke B (2002) MRI evaluation and functional assessment of brain injury after hypoxic ischemia in neonatal mice. Stroke 33:1405–1410

    Google Scholar 

  20. Heiland S, Sartor K, Martin E, Bardenheuer HJ, Plaschke K (2002) In vivo monitoring of age-related changes in rat brain using quantitative diffusion magnetic resonance imaging and magnetic resonance relaxometry. Neurosci Lett 334:157–160

    Google Scholar 

  21. de la Torre JC, Fortin T, Park GA, Butler KS, Kozlowski P, Pappas BA, de Socarraz H, Saunders JK, Richard MT (1992) Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats. Brain Res 582:186–195

    Google Scholar 

  22. de la Torre JC, Fortin T, Park GA, Saunders JK, Kozlowski P, Butler K, de Socarraz H, Pappas B, Richard M (1992) Aged but not young rats develop metabolic memory deficits after chronic brain ischaemia. Neurol Res 14:177–180

    Google Scholar 

  23. Sykova E, Mazel T, Simonova Z (1998) Diffusion constraints and neuron-glia interaction during aging. Exp Gerontol 33:837–851

    Google Scholar 

  24. Canese R, Podo F, Fortuna S, Lorenzini P, Michalek H (1997) Transient global brain ischemia in the rat: spatial distribution, extension, and evolution of lesions evaluated by magnetic resonance imaging. MAGMA 5:139–149

    Google Scholar 

  25. Canese R, Fortuna S, Lorenzini P, Podo F, Michalek H (1998) Transient global brain ischemia in young and aged rats: differences in severity and progression, but not localisation, of lesions evaluated by magnetic resonance imaging. MAGMA 7:28–34

    Google Scholar 

  26. Masoro EJ (1991) Use of rodents as models for the study of ‘normal aging’: conceptual and practical issue. Neurobiol Aging 12:639–643

    Google Scholar 

  27. Shukitt-Hale B, Casadesus G, Cantuti-Castelvetri I, Joseph JA (2001) Effect of age on object exploration, habituation and response to spatial and non spatial change. Behav Neurosci 115:1059–1064.

    Google Scholar 

  28. Tayebati SK, Di Tullio MA, Amenta F (2004) Age-related changes of muscarinic cholinergic receptor subtypes in the striatum of Fisher 344 rats. Exp Gerontol 39:217–223

    Google Scholar 

  29. Dewey SL, Volkow ND, Logan J, MacGregor RR, Fowler JS, Schlyer DJ, Bendriem B (1990) Age-related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET). J Neurosci Res 27:569–575

    Google Scholar 

  30. Lorenzini P, Pestalozza S, Fortuna S, Morelli M, Bisso GM, Michalek H (1996) Transient global cerebral hypoxia-ischemia in rats: age-related differences in neuronal damage and responsiveness of metabotropic glutamate receptors to excitatory amino acid agonists. Fund Clin Pharmacol 10:199

    Google Scholar 

  31. Fortuna S, Pestalozza S, Lorenzini P, Bisso GM, Morelli L, Michalek H (1997) Transient global brain ischemia-hypoxia in adult rats: neuronal damage, glial proliferation and alterations in inositol phospholipid hydrolysis. Neurochem Int 30:563– 569

    Google Scholar 

  32. Stejskal EO, Tanner JE (1965) Spin diffusion measurements: spin-echoes in the presence of a time-dependent field gradient. J Chem Phys 42:288–292

    CAS  Google Scholar 

  33. Toner CC, Milne AJ, Blatchford KL, McLaughlin DP, Stamford JA (2002) An assessment of the cerebroprotective potential of volatile anaesthetics using two independent methods in an in vitro model of cerebral ischaemia. Brain Res 958:390–398

    Google Scholar 

  34. Huisman TA (2003) Diffusion-weighted imaging: basic concepts and application in cerebral stroke and head trauma. Eur Radiol 13:2283–2297

    Article  PubMed  Google Scholar 

  35. Dijkhuizen RM, Knollema S, van der Worp B, Ter Horst GJ, De Wildt D, Berkelbach van der Sprenkel JW, Tulleken KAF, Nicolay K (1998) Dynamics of cerebral tissue injury and perfusion after temporary hypoxia-ischemia in the rat: evidence for region specific sensitivity and delayed damage. Stroke 29:695– 704

    CAS  PubMed  Google Scholar 

  36. Miyasaka N, Kuroiwa T, Zhao FY, Nagaoka T, Akimoto H, Yamada I, Kubota T, Aso T (2000) Cerebral ischemic hypoxia: discrepancy between apparent diffusion coefficients and histologic changes in rats. Radiology 215:199–204

    Google Scholar 

  37. van Dorsten FA, Olàh L, Schwindt W, Grüne M, Uhlenkuken U, Pillekanmp F, Hossmann KA, Hoehn M (2002) Dynamic changes of ADC, perfusion and NMR relaxation parameters in transient focal ischemia of rat brain. Magn Reson Med 47:97–104

    Google Scholar 

Download references

Acknowledgments.

This work was partially supported by ISS grant No. 0D2/C.

Author information

Affiliations

  1. Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    R. Canese, M. Giannini & F. Podo

  2. Department of Drug Research and Control, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    P. Lorenzini, S. Fortuna, M. T. Volpe & H. Michalek

Authors
  1. R. Canese
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Lorenzini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Fortuna
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. T. Volpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Giannini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Podo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. Michalek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Canese.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Canese, R., Lorenzini, P., Fortuna, S. et al. Age-dependent MRI-detected lesions at early stages of transient global ischemia in rat brain. MAGMA 17, 109–116 (2004). https://doi.org/10.1007/s10334-004-0072-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10334-004-0072-6

Keywords

  • Cerebral ischemia
  • Hypoxia
  • Magnetic resonance imaging
  • Diffusion
  • Aging
  • Rats