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The natural course of lesion development in brain ischemia

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Mechanisms of Secondary Brain Damage from Trauma and Ischemia

Part of the book series: Acta Neurochirurgica Supplements ((NEUROCHIRURGICA,volume 89))

Abstract

Histopathologic and NMR imaging studies show that focally ischemic brain lesions tend to increase in size over time. In animal models of stroke as well as in patients presenting with hemispheric stroke, considerable lesion growth was observed. In focal cerebral ischemia, lesions predominantly enlarge early (<12 hrs postinsult) and show complete ischemic injury due to pan necrosis in the vast majority of affected tissue. In global cerebral ischemia — a condition that is present after cardiac arrest — lesions appear late (>12 hrs) in selectively vulnerable brain regions and neurons are damaged by apoptosis. The short resuscitation time of the brain explains why periods of global ischemia result in widespread and global loss of energy metabolites combined with diffuse brain edema and global damage. Mechanisms involved in lesion growth include excitotoxicity, peri-infarct depolarizations, lactacidosis, microcirculatory disturbances, and flow-metabolism uncoupling among others. Problems involved in the subject under focus are related to maturation phenomena of injury and the different imaging modalities (metabolic imaging, NMR imaging, positron emission tomography) that require a subtly differentiated interpretation of the alterations observed.

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References

  1. Alexis NE, Back T, Zhao W, Dietrich WD, Watson BD, Ginsberg MD (1996) Neuro-behavioral consequences of induced spreading depression following photothrombotic middle cerebral artery occlusion. Brain Res 706: 273–282

    Article  CAS  PubMed  Google Scholar 

  2. Arbelaez A, Castillo M, Mukherji SK (1999) Diffusion-weighted MR imaging of global cerebral anoxia. Am J Neuroradiol 20: 999–1007

    CAS  PubMed  Google Scholar 

  3. Astrup J, Siesjö BK, Symon L (1981) Thresholds in cerebral ischemia — The ischemic penumbra. Stroke 12: 723–725

    Article  CAS  PubMed  Google Scholar 

  4. Back T, Ginsberg MD, Dietrich WD, Watson BD (1996) Induction of spreading depression in the ischemic hemisphere following experimental middle cerebral artery occlusion: Effect on infarct morphology. J Cereb Blood Flow Metab 16: 202–213

    Article  CAS  PubMed  Google Scholar 

  5. Back T, Hirsch JG, Szabo K, Gass A (2000) Failure to demonstrate peri-infarct depolarizations by repetitive MR diffusion imaging in acute human stroke. Stroke 31: 2901–2906

    Article  CAS  PubMed  Google Scholar 

  6. Back T, Hoehn-Berlage M, Kohno K, Hossmann K-A (1994) Diffusion NMR imaging in experimental stroke: correlation with cerebral metabolites. Stroke 25: 494–500

    Article  CAS  PubMed  Google Scholar 

  7. Back T, Hoehn M, Mies G, Busch E, Schmitz B, Kohno K, Hossmann KA (2000) Penumbral tissue alkalosis in focal cerebral ischemia: relationship to energy metabolism, blood flow, and steady potential. Ann Neurol 47: 485–492

    Article  CAS  PubMed  Google Scholar 

  8. Back T, Kohno K, Hossmann K-A (1994) Cortical negative DC deflections following middle cerebral artery occlusion and KC1-induced spreading depression: Effect on blood flow, tissue oxygenation and electroencephalogram. J Cereb Blood Flow Metab 14: 12–19

    Article  CAS  PubMed  Google Scholar 

  9. Back T, Zhao W, Ginsberg MD (1995) Three-dimensional image analysis of brain glucose metabolism/blood flow uncoupling and its electrophysiological correlates in the acute ischemic penumbra following middle cerebral artery occlusion. J Cereb Blood Flow Metab 15: 566–577

    Article  CAS  PubMed  Google Scholar 

  10. Baird AE, Benfield A, Schlaug G, Siewert B, Lövblad K-O, Edelman RR, Warach S (1997) Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging. Ann Neurol 41: 581–589

    Article  CAS  PubMed  Google Scholar 

  11. Barber PA, Darby DG, Desmond PM, Yang Q, Gerraty RP. Jolley D, Donnan GA, Tress BM, Davis SM (1998) Prediction of stroke outcome with echoplanar perfusion-and diffusionweighted MRI. Neurology 51: 418–426

    Article  CAS  PubMed  Google Scholar 

  12. Berek K, Lechleitner P, Luef G, Felber S, Saltuari L, Schinnerl A, Traweger C, Dienstl F, Aichner F (1995) Early determination of neurological outcome after prehospital cardiopulmonary resuscitation. Stroke 26: 543–549

    Article  CAS  PubMed  Google Scholar 

  13. Bottiger BW, Schmitz B, Wiessner C, Vogel P, Hossmann KA (1998) Neuronal stress response and neuronal cell damage after cardiocirculatory arrest in rats. J Cereb Blood Flow Metab 18: 1077–1087

    Article  CAS  PubMed  Google Scholar 

  14. Brinker G, Franke C, Hoehn M, Uhlenkuken U, Hossmann KA (1999) Thrombolysis of cerebral clot embolism in rat: effect of treatment delay. NeuroReport 10: 3269–3272

    Article  CAS  PubMed  Google Scholar 

  15. Busch E, Gyngell M, Eis M, Hoehn-Berlage M, Hossmann K-A (1996) Potassium-induced cortical spreading depression during focal cerebral ischemia in rats: contribution to lesion growth assessed by diffusion-weighted NMR and biochemical imaging. J Cereb Blood Flow Metab 16: 1090–1099

    Article  CAS  PubMed  Google Scholar 

  16. Choi DW (1992) Excitotoxic cell death. J Neurobiol 23: 1261–1276

    Article  CAS  PubMed  Google Scholar 

  17. Clark RK, Lee EV, Fish CJ, White RF, Price WJ, Jonak ZL, Feuerstein GZ, Barone FC (1993) Development of tissue damage, inflammation and resolution following stroke: an immunohistochemical and quantitative planimetric study. Brain Res Bull 31: 565–572

    Article  CAS  PubMed  Google Scholar 

  18. del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA, Gent M (1998) PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in acute cerebral thromboembolism. Stroke 29: 4–11

    Article  PubMed  Google Scholar 

  19. Franke C, Brinker G, Pillekamp F, Hoehn M (2000) Probability of metabolic tissue recovery after thrombolytic treatment of experimental stroke: a magnetic resonance spectroscopic imaging study in rat brain. J Cereb Blood Flow Metab 20: 583–591

    Article  CAS  PubMed  Google Scholar 

  20. Garcia JH, Kamijyo Y (1974) Cerebral infarction evolution of histopathological changes after occlusion of the middle cerebral artery in primates. Exp Neurol 33: 408–421

    CAS  Google Scholar 

  21. Garcia JH, Yoshida Y, Chen H, Li Y, Zhang ZG, Lian J, Chen S, Chopp M (1993) Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am J Pathol 142: 623–635

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Ginsberg MD, Back T, Zhao W (1995) Three-dimensional metabolic and hemodynamic imaging of the normal and ischemic rat brain. Acta Neurochir (Wien) 66: 44–49

    Google Scholar 

  23. Grubb NR, Fox KA, Smith K, Best J, Blane A, Ebmeier KP, Glabus MF, O’Carroll RE (2000) Memory impairment in outof-hospital cardiac arrest survivors is associated with global reduction in brain volume, not focal hippocampal injury. Stroke 31: 1509–1514

    Article  CAS  PubMed  Google Scholar 

  24. Gyngell M, Back T, Hoehn-Berlage M, Kohno K, Hossmann K-A (1994) Transient cell depolarization after permanent middle cerebral artery occlusion: An observation by diffusionweighted MRI and localized 1H-MRS. Magn Reson Med 31: 337–341

    Article  CAS  PubMed  Google Scholar 

  25. Gyngell M, Busch E, Schmitz B, Kohno K, Back T, Hoehn-Berlage M, Hossmann K-A (1995) Evolution of acute focal cerebral ischaemia in rats observed by localised 1H-MRS, diffusion-weighted MRI, and electrophysiological monitoring. NMR Biomed 8: 206–214

    Article  CAS  PubMed  Google Scholar 

  26. Hakim AM, Hogan MJ, Carpenter S (1992) Time course of cerebral blood flow and histological outcome after focal cerebral ischemia in rats. Stroke 23: 1138–1143

    Article  CAS  PubMed  Google Scholar 

  27. Heiss W-D, Graf R, Wienhard K, Lottgen J, Saito R, Fujita T, Rosner G. Wagner R (1994) Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats. J Cereb Blood Flow Metab 14: 892–902

    Article  CAS  PubMed  Google Scholar 

  28. Heiss W-D, Huber M, Fink GR, Herholz K, Pietrzyk U, Wagner R, Wienhard K (1992) Progressive derangement of periinfarct viable tissue in ischemic stroke. J Cereb Blood Flow Metab 12: 193–203

    Article  CAS  PubMed  Google Scholar 

  29. Heiss WD, Thiel A, Grond M, Graf R (1999) Contribution of immediate and delayed ischaemic damage to the volume of final infarcts. Lancet 353: 1677–1678

    Article  CAS  PubMed  Google Scholar 

  30. Hoehn-Berlage M, Norris DG, Kohno K, Mies G, Leibfritz D, Hossmann KA (1995) Evolution of regional changes in apparendiffusion coefficient during focal ischemia of rat brain: the relationship of quantitative diffusion NMR imaging to reduction in cerebral blood flow and metabolic disturbances. J Cereb Blood Flow Metab 15: 1002–1011

    Article  CAS  PubMed  Google Scholar 

  31. Hossmann KA, Fischer M, Bockhorst K, Hoehn-Berlage M (1994) NMR imaging of the apparent diffusion coefficient (ADC) for the evaluation of metabolic suppression and recovery after prolonged cerebral ischemia. J Cereb Blood Flow Metab 14:723–731

    Article  CAS  PubMed  Google Scholar 

  32. Iijima T, Mies G, Hossmann K-A (1992) Repeated negative DC deflections in rat cortex following middle cerebral artery occlusion are abolished by MK-801: effect on volume of ischemic injury. J Cereb Blood Flow Metab 12: 727–733

    Article  CAS  PubMed  Google Scholar 

  33. Karonen JO, Vanninen RL, Liu Y, Ostergaard L, Kuikka JT, Nuutinen J, Vanninen EJ, Partanen PLK, Vainio PA, Korhonen K (1999) Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke. Ischemic penumbra predicts infarct growth. Stroke 30: 1583–1590

    Article  CAS  PubMed  Google Scholar 

  34. Kohno K, Hoehn-Berlage M, Mies G, Back T, Hossmann K-A (1995) Relationship between diffusion-weighted magnetic resonance images, cerebral blood flow and energy state in experimental brain infarction. Magn Reson Imag 13: 73–80

    Article  CAS  Google Scholar 

  35. Kummer Rv, Holle R, Rosin L, Forsting M, Hacke W (1995) Does arterial recanalization improve outcome in carotid territory stroke? Stroke 26: 581–587

    Article  Google Scholar 

  36. Leao AAP (1944) Spreading depression of activity in the cerebral cortex. J Neurophysiol 7: 359–390

    Google Scholar 

  37. Li Y, Chopp M, Jiang N, Xao F, Zaloga C (1995) Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 15:389–397

    Article  CAS  PubMed  Google Scholar 

  38. Linnik MD, Zobrist RH, Hatfield MD (1993) Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke 24: 2002–2009

    Article  CAS  PubMed  Google Scholar 

  39. Mies G, Iijima T, Hossmann K-A (1993) Correlation between periinfarct DC shifts and ischemic neuronal damage in rat. NeuroReport 4: 709–711

    Article  CAS  PubMed  Google Scholar 

  40. Minematsu K, Li L, Sotak CH, Davis MA, Fisher M (1992) Reversible focal ischemic injury demonstrated by diffusionweighted MR imaging in rats. Stroke 23: 1304–1311

    Article  CAS  PubMed  Google Scholar 

  41. Nedergaard M, Astrup J (1986) Infarct rim: Effect of hyperglycemia on direct current potential and [14C]2-deoxyglucose phosphorylation. J Cereb Blood Flow Metab 6: 607–615

    Article  CAS  PubMed  Google Scholar 

  42. Nedergaard M, Gjedde A, Diemer NH (1986) Focal ischemia of the rat brain: autoradiographic determination of cerebral glucose utilization, glucose content, and blood flow. J Cereb Blood Flow Metab 6: 414–424

    Article  CAS  PubMed  Google Scholar 

  43. Neumann-Haefelin T, Wittsack HJ, Wenserski F, Siebler M, Seitz R, Modder U, Freund H-J (1999) Diffusion-and perfusion-weighted MRI. The DWI/PWI mismatch region in acute stroke. Stroke 30: 1591–1597

    Article  CAS  PubMed  Google Scholar 

  44. Ouyang YB, Tan Y, Comb M, Liu CL, Martone ME, Siesjo BK, Hu BR (1999) Survival-and death-promoting events after transient cerebral ischemia: phosphorylation of Akt, release of cytochrome C and Activation of caspase-like proteases. J Cereb Blood Flow Metab 19: 1126–1135

    Article  CAS  PubMed  Google Scholar 

  45. Park CK, Nehls DG, Graham DI, Teasdale GM, McCulloch J (1988) The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat. Ann Neurol 24: 543–551

    Article  CAS  PubMed  Google Scholar 

  46. Roether J, de Crespigny A, D’Arceuil H, Iwai K, Moseley ME (1996) Recovery of apparent diffusion coefficient after ischemia-induced spreading depression relates to cerebral perfusion gradient. Stroke 27: 980–987

    Article  Google Scholar 

  47. Schmidt-Kästner R, Paschen W, Ophoff BG, Hossmann KA (1989) A modified four-vessel occlusion model for inducing incomplete forebrain ischemia in rats. Stroke 20: 938–946

    Article  PubMed  Google Scholar 

  48. Schüler OG, Plesnila N, Otto D, Baethmann AJ, Back T (2001) Early thrombolysis inhibits peri-infarct depolarizations in embolic MCA occlusion. NeuroReport 12(18): 3943–3946

    Article  PubMed  Google Scholar 

  49. Terai S, Hori T, Miake S, Tamaki K, Saishoji A (2000) Mechanism in progressive lacunar infarction: a case report with magnetic resonance imaging. Arch Neurol 57: 255–258

    Article  CAS  PubMed  Google Scholar 

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© 2004 Springer-Verlag Wien

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Back, T., Schüler, O.G. (2004). The natural course of lesion development in brain ischemia. In: Baethmann, A., Eriskat, J., Lehmberg, J., Plesnila, N. (eds) Mechanisms of Secondary Brain Damage from Trauma and Ischemia. Acta Neurochirurgica Supplements, vol 89. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0603-7_7

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  • DOI: https://doi.org/10.1007/978-3-7091-0603-7_7

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-7206-3

  • Online ISBN: 978-3-7091-0603-7

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