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.
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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 29:336–345
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 242:17–23
Brown AW, Brierley JB (1972) Anoxic-ischemic cell change in rat brain. Light microscopic and fine-structural observations. J Neurol Sci 16:59–84
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 118:109–116
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 7:745–751
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
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 144:188–199
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 12:257–269
Guilian D, Baker TJ (1985) Peptides released by ameboid microglia regulate astroglial proliferation. J Cell Biol 101:2411–2415
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 82:123–136
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 9:1693–1700
Ito U, Spatz M, Walker JT Jr, Klatzo I (1975) Experimental cerebral ischemia in mongolian gerbils. I. Light microscopic observations. Acta Neuropathol (Berl) 32:209–223
Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69
Levine S (1960) Anoxic-ischemic encephalopathy in rats. Am J Pathol 36:1–17
Ling EA (1976) Some aspects of amoeboid microglia in the corpus callosum and neighboring regions of neonatal rats. J Anat 121:29–45
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: 1469–1475
Morioka T, Kalehua AN, Streit WJ (1991) The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. J Cereb Blood Flow Metab 11:966–973
Morioka T, Kalehua AN, Streit WJ (1993) Characterization of microglial reaction after middle cerebral artery occlusion in rat brain. J Comp Neurol 327:123–132
Murabe Y, Sano Y (1982) Morphological studies on neuroglia. VI. Postnatal development of microglial cells. Cell Tissue Res 225:469–485
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 13:1553
Persson L, Hårdemark H-G, Bolander HG, Hillered L, Olsson Y (1989) Neurologic and neuropathologic outcome after middle cerebral artery occlusion in rats. Stroke 20:641–645
Petito CK, Morgello S, Felix CJ, Lesser ML (1990) The two patterns of reactive astrocytosis in postischemic rat brain. J Cereb Blood Flow Metab 10:850–859
Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11:491–498
Rice JE, Vannucci RC, Brierley JB (1981) The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 9:131–141
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 59:231–235
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 11:106–113
Salford LG, Plum F, Brierley JB (1973) Graded hypoxiaoligemia in rat brain. II. Neuropathological alterations and their implications. Arch Neurol 29:234–238
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 38:527–540
Schwartz PH, Massarweb WF, Vinters HV, Wasterlain CG (1992) A rat model of severe neonatal hypoxic-ischemic brain injury. Stroke 23:539–546
Sherwood NM, Timiras PS (1970) A stereotaxic atlas of the developing rat brain. University of California Press, Berkley
Streit WJ, Kreutzberg GW (1987) Lectin binding by resting and reactive microglia. J Neurocytol 16:249–260
Towfighi J, Yager JY, Housman C, Vannucci RC (1991) Neuropathology of remote hypoxic-ischemic damage in the immature rat. Acta Neuropathol 81:578–587
Yoshimine T, Morimoto K, Brengman JM, Homburger HA, Mogami H, Yanagihara T (1985) Immunohistochemical investigation of cerebral ischemia during recirculation. J Neurosurg 63:922–928
Young RSK, Yagel SK, Towfighi J (1983) Systemic and neuropathologic effects of E. Coli endotoxin in neonatal dogs. Pediatr Res 17:349–353
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Towfighi, J., Zec, N., Yager, J. et al. Temporal evolution of neuropathologic changes in an immature rat model of cerebral hypoxia: a light microscopic study. Acta Neuropathol 90, 375–386 (1995). https://doi.org/10.1007/BF00315011
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DOI: https://doi.org/10.1007/BF00315011