Skip to main content
Log in

The heterogeneous temporal evolution of focal ischemic neuronal damage in the rat

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Male Fisher rats (n=61) underwent permanent focal cerebral ischemia induced by left middle cerebral artery (MCA) occlusion, in conjunction with ipsilateral common carotid artery ligation. The experiments were terminated at time points ranging from immediately following occlusion to 30 days post MCA occlusion. A coronal histological section, in close proximity to the site of the arterial occlusion, was taken from each brain and divided into six areas encompassing the affected cortex and caudate putamen. Each area was analyzed for ischemic damage according to a grading scale that reflects changes in neuronal morphology. Differential neuronal counts were also made on a 0.5-mm2 field in each of the six areas. The areas closest to the occluded vessel showed accelerated ischemic damage between 8 and 12 h after occlusion, leaving open the possibility that before 8 h, therapeutic intervention may be effective. After 12 h, changes in these areas progressed to complete necrosis and eventual cavitation with a complete loss of neurons after 10 days. The areas more peripheral to the occluded vessel exhibited mild ischemic damage, with an apparent reversal of damage grading at later time points and no loss of neurons. This reversal of ischemic damage in the peripheral areas is suggestive of a histological equivalent of the penumbra.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

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

    Google Scholar 

  2. Bose B, Jones SC, Lorig R, Friel HT, Weinstein M, Little JR (1988) Evolving focal cerebral ischemia in cats: spatial correlation of nuclear magnetic resonance imaging, cerebral blood flow, tetrazolium staining, and histopathology. Stroke 19:28–37

    Google Scholar 

  3. Brierley JB (1976) Cerebral hypoxia. In: Adams JH, Corsellis JAN, Duchen LW (eds) Greenfield's neuropathology. Wiley and Sons, New York, pp 43–85

    Google Scholar 

  4. Brint S, Jacewicz M, Kiessling M, Tanabe J, Pulsinelli W (1988) Focal brain ischemia in the rat: methods for reproducible neocortical infarction using tandem occlusion of the distal middle cerebral and ipsilateral common carotid arteries. J Cereb Blood Flow Metab 8:474–485

    Google Scholar 

  5. Brown AQ Brierley JB (1966) Evidence for early anoxicischemic cell damage in the rat brain. Experientia 22:546–547

    Google Scholar 

  6. Brown AW, Brierley JB (1968) The nature distribution and earliest stages of anoxic-ischemic nerve cell damage in the rat brain as defined by the optical microscope. Br J Exp Pathol 49:87–106

    Google Scholar 

  7. Cammermeyer J (1978) Is the solitary dark neuron a manifestation of postmortem trauma to the brain inadequately fixed by perfusion? Histochemistry 56:97–115

    Google Scholar 

  8. Chopp M, Li Y, Zhang ZG, Freytag SO (1992) p53 expression in brain after middle cerebral artery occlusion in the rat. Biochem Biophysic Res Commun 182:1201–1207

    Google Scholar 

  9. Crowell RM, Marcoux FW, DeGirolami U (1981) Variability and reversibility of focal cerebral ischemia in unanesthetized monkeys. Neurology 31:1295–1302

    Google Scholar 

  10. DeGirolami U, Crowell RM, Marcoux FW (1984) Selective necrosis and total necrosis in focal cerebral ischemia: neuropathologic observations on experimental middle cerebral artery occlusion in the macaque monkey. J Neuropathol Exp Neurol 43:57–71

    Google Scholar 

  11. Duverger D, Mackenzie ET (1988) The quantification of cerebral infarction following focal ischemia in the rat: influence of strain, arterial pressure, blood glucose concentration and age. J Cereb Blood Flow Metab 8:449–461

    Google Scholar 

  12. Ebhardt G, Mies G, Auer LM, Traupe H, Heiss WD (1983) neuronal injury following permanent middle cerebral artery occlusion in cats. Acta Neuropathol (Berl) 60:70–74

    Google Scholar 

  13. Eke A, Conger KA, Anderson M, Garcia JH (1990) Histologic assessment of neurons in rat models of cerebral ischemia. Stroke 21:299–304

    Google Scholar 

  14. Garcia JH, Kamijyo Y (1974) Cerebral infarction evolution of histopathologic changes after occlusion of a middle artery in primates. J Neuropathol Exp Neurol 33:408–21

    Google Scholar 

  15. Garcia JH, Yoshida Y, Chen H, Li Y, Zhang Z, Lian J, Chen S, Chopp M (1992) Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am J Pathol (in press)

  16. Hossmann KA, Schuier FJ (1980) Experimental brain infarcts in cats. I. Pathophysiological observations. Stroke 11:583–592

    Google Scholar 

  17. Iizuka H, Sakatani K, Young W (1989) Selective cortical neuronal damage after middle cerebral artery occlusion in rats. Stroke 20:1516–1523

    Google Scholar 

  18. Jacewicz M, Tanabe J, Pulsinelli W (1992) The CBF threshold and dynamics for focal cerebral infarction in spontaneously hypertensive rats. J Cereb Blood Flow Metab 12:359–370

    Google Scholar 

  19. Jakob A (1927) Normale und pathologische Anatomie und Histologie des Grosshirns. In: Deuticke F (ed) Normale Anatomie und Histologie und Allgemeine Histopathologie des Grosshirns, vol 1. Leipzig, Germany Deuticke pp 1–193

    Google Scholar 

  20. Jenkins LW, Povlishock JT, Lewelt W, Miller JD, Becker DP (1981) The role of postischemic recirculation in the development of ischemic neuronal injury following complete cerebral ischemia. Acta Neuropathol (Berl) 55:205–220

    Google Scholar 

  21. Kirino T, Tamura A, Sano K (1984) Delayed neuronal death in the rat hippocampus following transient forebrain ischemia. Acta Neuropathol (Berl) 64:139–147

    Google Scholar 

  22. Knight RA, Ordidge RJ, Helpern JA, Chopp M, Rodolosi LC, Peck D (1991) Temporal evolution of ischemic damage in rat brain measured by proton nuclear magnetic resonance imaging. Stroke 22:802–808

    Google Scholar 

  23. McGee-Russell SM, Brown AW, Brierley JB (1970) A combined light and electron microscope study of early anoxicischemic cell change in rat brain. Brain Res 20:193–200

    Google Scholar 

  24. Meier-Ruge W, Theodore D, Abraham J (1987) Enzyme histochemical investigation of the pathogenesis of ischemic brain lesions in primates and its clinical consequences. In: Cervós-Navarro J, Ferszt R (eds) Stroke and microcirculation. Raven Press, New York, pp 35–38

    Google Scholar 

  25. Meyer FB, Sundt TM, Yanagihara T, Anderson RE (1987) Focal cerebral ischemia: pathophysiologic mechanisms and rationale for future avenues of treatment. Mayo Clin Proc 62:35–55

    Google Scholar 

  26. Nedergaard M (1987) Neuronal injury in the infarct border: a neuropathological study in the rat. Acta Neuropathol (Berl) 73:267–274

    Google Scholar 

  27. Nedergaard M (1988) Mechanisms of brain damage in focal cerebral ischemia. Acta Neurol Scand 77:81–101

    Google Scholar 

  28. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, second edn. Academic Press, Orlando

    Google Scholar 

  29. Olsen TS (1986) Regional cerebral blood flow after occlusion of the middle cerebral artery. Acta Neurol Scand 73:321–337

    Google Scholar 

  30. Persson L, Hardemark HG, Bolander HG, Hillered L, Olsson Y (1989) Neurologic and neuropathologic outcome after middle cerebral artery occlusion in rats. Stroke 20:641–645

    Google Scholar 

  31. Petito CK, Lapinski RL (1986) Postischemic alterations in ultrastructural cytochemistry of neuronal golgi apparatus. Lab Invest 55:696–702

    Google Scholar 

  32. Petito CK, Pulsinelli WA (1984) Delayed neuronal recovery and neuronal death in rat hippocampus following severe cerebral ischemia: possible relationship to abnormalities in neuronal processes. J Cereb Blood Flow Metab 4:194–205

    Google Scholar 

  33. Petito CK, Pulsinelli WA (1984) Sequential development of reversible and irreversible neuronal damage following cerebral ischemia. J Neuropathol Exp Neurol 43:141–153

    Google Scholar 

  34. Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11:491–498

    Google Scholar 

  35. Rubino GJ, Young W (1988) Ischemic cortical lesions after permanent occlusion of individual middle cerebral artery branches in rats. Stroke 19:870–877

    Google Scholar 

  36. Searle J, Kerr JFR, Bishop CJ (1992) Necrosis and Apoptosis: distinct modes of cell death with fundamentally different significance. Pathol Annu 17:229–259

    Google Scholar 

  37. Selman WR, Ricci AJ Crumrine RC, LaManna JC, Ratcheson RA, Lust WD (1990) The evolution of focal ischemic damage: a metabolic analysis. Metab Brain Dis 5:33–44

    Google Scholar 

  38. Shiino A, Harada K, Handa J, (1989) Focal brain ischemia model in rats. An experimental study. Surg Neurol 31:203–208

    Google Scholar 

  39. Smith ML, Auer RN, Siesjö BK (1984) The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia. Acta Neuropathol (Berl) 64:319–332

    Google Scholar 

  40. Spielmeyer W (1922) Histopathologie des Nervensystems. Springer-Verlag, Berlin pp 74–79

    Google Scholar 

  41. Tyson GW, Teasdale GM, Graham DI, McCulloch J (1984) Focal cerebral ischemia in the rat: topography of hemodynamic and histopathological changes. Ann Neurol 15:559–567

    Google Scholar 

  42. Yamamoto K, Yoshimine T, Yanagihara T (1985) Cerebral ischemia in rabbit: a new experimental model with immunohistochemical investigation. J Cereb Blood Flow Metab 5:529–536

    Google Scholar 

  43. Yoshimine T, Yanagihara T (1983) Regional cerebral ischemia by occlusion of the posterior communicating artery and the middle cerebral in gerbils. T Neurosurg 58:362–367

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by NIH Grants NS23393 and NS29463

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dereski, M.O., Chopp, M., Knight, R.A. et al. The heterogeneous temporal evolution of focal ischemic neuronal damage in the rat. Acta Neuropathol 85, 327–333 (1993). https://doi.org/10.1007/BF00227730

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00227730

Key words

Navigation