Acta Neuropathologica

, Volume 90, Issue 4, pp 375–386 | Cite as

Temporal evolution of neuropathologic changes in an immature rat model of cerebral hypoxia: a light microscopic study

  • Javad Towfighi
  • Natasa Zec
  • Jerry Yager
  • Cathy Housman
  • Robert C. Vannucci
Regular Paper

Abstract

The sequential evolution of neuropathologic changes was studied in an immature model of cerebral hypoxia-ischemia. Accordingly, 7-day postnatal rats were subjected to unilateral common carotid artery ligation combined with 2 h of hypoxia (breathing in 8% oxygen) and their brains were examined by light microscopy at recovery intervals ranging from 0 to 3 weeks. Immediately following hypoxia, a large area with a pale staining border was noted occupying most of the cerebral hemisphere ipstlateral (IL) to the occluded common carotid artery; in approximately half of the brains the dorsomedial cortex of the contralateral (CL) hemisphere was also involved. Most neurons in the pale area had nuclei containing a coarse granular condensation of chromatin. Within a few hours, the majority of neurons in the IL hemisphere had developed pyknotic nuclei and clear or eosinophilic perikarya. After 24 h these changes had evolved in the majority of brains into coagulation necrosis (infarction) in the IL hemisphere sphere and foci of selective neuronal necrosis in the CL ortex. Within a few days infarcts became partially cavirated, and by 3 weeks a smooth-walled cystic infarct had developed. Activated microglia/macrophages and reactive astrocytes were first seen at 4 and 24 h, respectively. No parenchymal neutrophilic infiltrate was seen at any time point.

Key words

Brain Hypoxia-ischemia Pathology Perinatal Rats 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Barone FC, Hillegass LM, Price WJ, White RF, Lee EV, Feuerstein GZ, Sarau HM, Clark RK, Griswold DE (1991) Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue: myeloperoxidase activity assay and histologic verification. J Neurosci Res 29:336–345Google Scholar
  2. 2.
    Bois M du, Bowman PD, Goldstein GW (1985) Cell proliferation after ischemic injury in gerbil brain. An immunocytochemical study and autoradiographic study. Cell Tissue Res 242:17–23Google Scholar
  3. 3.
    Brown AW, Brierley JB (1972) Anoxic-ischemic cell change in rat brain. Light microscopic and fine-structural observations. J Neurol Sci 16:59–84Google Scholar
  4. 4.
    Chen H, Chopp M, Schultz L, Bodzin G, Garcia JH (1993) Sequential neuronal and astrocytic changes after transient middle cerebral artery occlusion in the rat. J Neurol Sci 118:109–116Google Scholar
  5. 5.
    De Leo J, Toth L, Schubert P, Rudolphi K, Kreutzberg GW (1987) Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the mongolian gerbil and protection by propentofylline (HWA285). J Cereb Blood Flow Metab 7:745–751Google Scholar
  6. 6.
    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 142:623–635Google Scholar
  7. 7.
    Garcia JH, Liu KF, Yoshida Y, Lian J, Chen S, Zoppo GJ del (1994) Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). Am J Pathol 144:188–199Google Scholar
  8. 8.
    Gehrmann J, Bonnekoh P, Miyazawa T, Hossmann K-A, Kreutzberg GW (1992) Immunocytochemical study of an early microglial activation in ischemia. J Cereb Blood Flow Metab 12:257–269Google Scholar
  9. 9.
    Guilian D, Baker TJ (1985) Peptides released by ameboid microglia regulate astroglial proliferation. J Cell Biol 101:2411–2415Google Scholar
  10. 10.
    Grimaldi R, Zoli M, Agnati LF, Ferraguti F, Fuxe K, Toffano G, Zini I (1990) Effects of transient forebrain ischemia on peptidergic neurons and astroglial cells: evidence for recovery of peptide immunoreactivities in neocortex and striatum but not hippocampal formation. Exp Brain Res 82:123–136Google Scholar
  11. 11.
    Ikonomidou C, Price MT, Mosinger JL, Frierdich G, Labruyere J, Shahid Salles K, Olney JW (1989) Hypobaric-ischemic conditions produce glutamate-like cytopathology in infant rat brain. J Neurosci 9:1693–1700Google Scholar
  12. 12.
    Ito U, Spatz M, Walker JT Jr, Klatzo I (1975) Experimental cerebral ischemia in mongolian gerbils. I. Light microscopic observations. Acta Neuropathol (Berl) 32:209–223Google Scholar
  13. 13.
    Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69Google Scholar
  14. 14.
    Levine S (1960) Anoxic-ischemic encephalopathy in rats. Am J Pathol 36:1–17Google Scholar
  15. 15.
    Ling EA (1976) Some aspects of amoeboid microglia in the corpus callosum and neighboring regions of neonatal rats. J Anat 121:29–45Google Scholar
  16. 16.
    Matsuo Y, Onodera H, Shiga Y, Nakamura M, Ninomiya M, Kihara T, Kogure K (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke 25: 1469–1475Google Scholar
  17. 17.
    Morioka T, Kalehua AN, Streit WJ (1991) The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. J Cereb Blood Flow Metab 11:966–973Google Scholar
  18. 18.
    Morioka T, Kalehua AN, Streit WJ (1993) Characterization of microglial reaction after middle cerebral artery occlusion in rat brain. J Comp Neurol 327:123–132Google Scholar
  19. 19.
    Murabe Y, Sano Y (1982) Morphological studies on neuroglia. VI. Postnatal development of microglial cells. Cell Tissue Res 225:469–485Google Scholar
  20. 20.
    Olney JM, Grey G, Frierdich G, Shahid Salles K, Labruyere J, Price MT, Olney JW (1987) Hypoxia-ischemia causes glutamate-like neuropathological changes in infant rat brain. Soc Neurosci Abstr 13:1553Google Scholar
  21. 21.
    Persson L, Hårdemark H-G, Bolander HG, Hillered L, Olsson Y (1989) Neurologic and neuropathologic outcome after middle cerebral artery occlusion in rats. Stroke 20:641–645Google Scholar
  22. 22.
    Petito CK, Morgello S, Felix CJ, Lesser ML (1990) The two patterns of reactive astrocytosis in postischemic rat brain. J Cereb Blood Flow Metab 10:850–859Google Scholar
  23. 23.
    Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11:491–498Google Scholar
  24. 24.
    Rice JE, Vannucci RC, Brierley JB (1981) The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 9:131–141Google Scholar
  25. 25.
    Ringel M, Bryan RM, Vannucci RC (1991) Regional blood flow during hypoxia-ischemia in the immature rat; comparison of iodoantipyrine and iodoamphetamine as radioactive tracers. Dev Brain Res 59:231–235Google Scholar
  26. 26.
    Rischke R, Krieglstein J (1991) Postischemic neuronal damage causes astroglial activation and increase in local cerebral glucose utilization of rat hippocampus. J Cereb Blood Flow Metab 11:106–113Google Scholar
  27. 27.
    Salford LG, Plum F, Brierley JB (1973) Graded hypoxiaoligemia in rat brain. II. Neuropathological alterations and their implications. Arch Neurol 29:234–238Google Scholar
  28. 28.
    Schmidt-Kastner R, Szymas J, Hossmann K-A (1990) Immunohistochemical study of glial reaction and serum-protein extravasation in relation to neuronal damage in rat hippocampus after ischemia. Neuroscience 38:527–540Google Scholar
  29. 29.
    Schwartz PH, Massarweb WF, Vinters HV, Wasterlain CG (1992) A rat model of severe neonatal hypoxic-ischemic brain injury. Stroke 23:539–546Google Scholar
  30. 30.
    Sherwood NM, Timiras PS (1970) A stereotaxic atlas of the developing rat brain. University of California Press, BerkleyGoogle Scholar
  31. 31.
    Streit WJ, Kreutzberg GW (1987) Lectin binding by resting and reactive microglia. J Neurocytol 16:249–260Google Scholar
  32. 32.
    Towfighi J, Yager JY, Housman C, Vannucci RC (1991) Neuropathology of remote hypoxic-ischemic damage in the immature rat. Acta Neuropathol 81:578–587Google Scholar
  33. 33.
    Yoshimine T, Morimoto K, Brengman JM, Homburger HA, Mogami H, Yanagihara T (1985) Immunohistochemical investigation of cerebral ischemia during recirculation. J Neurosurg 63:922–928Google Scholar
  34. 34.
    Young RSK, Yagel SK, Towfighi J (1983) Systemic and neuropathologic effects of E. Coli endotoxin in neonatal dogs. Pediatr Res 17:349–353Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Javad Towfighi
    • 1
  • Natasa Zec
    • 3
  • Jerry Yager
    • 4
  • Cathy Housman
    • 1
  • Robert C. Vannucci
    • 2
  1. 1.Department of PathologyThe Pennsylvania State University College of Medicine, The Milton S. Hershey Medical CenterHersheyUSA
  2. 2.Department of PediatricsThe Pennsylvania State University College of Medicine, The Milton S. Hershey Medical CenterHersheyUSA
  3. 3.Department of PathologyHarvard Medical SchoolBostonUSA
  4. 4.Department of Pediatrics, Royal University HospitalUniversity of SaskatoonCanada

Personalised recommendations