Abstract
Activation of glial cells and white matter changes (rarefaction of the white matter) induced in the rat brain by permanent bilateral occlusion of the commom carotid arteries were immunohistochemically investigated up to 90 days. One day after ligation of the arteries, expression of the major histocompatibility complex (MHC) class I antigen in microglia increased in the white matter including the optic nerve, optic tract, corpus callosum, internal capsule, anterior commissure and traversing fiber bundles of the caudoputamen. After 3 days of occlusion, MHC class I antigen was still elevated and in addition MHC class II antigen and leukocyte common antigen were up-regulated in the microglia in these same regions. Astroglia, labeled with glial fibrillary acidic protein, increased in number in these regions after 7 days of occlusion. A few lymphocytes, labeled with CD4 or CD8 antibodies, were scattered in the neural parenchyma 1 h after occlusion. Activation of glial cells and infiltration of lymphocytes persisted after 90 days of occlusion in the white matter and the retinofugal pathway. However, cellular activation and infiltration in microinfarcts of the gray matter was less extensive and was substantially diminished 30 days after occlusion. The white matter changes were most intense in the optic nerve and optic tract, moderate in the medial part of the corpus callosum, internal capsule and anterior commissure, and slight in the fiber bundles of the caudoputamen. These results indicated that chronic cerebral hypoperfusion induced glial activation preferentially in the white matter. This activation seemed to be an early indicator of the subsequent changes in the white matter.
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Brightman MW, Klatzo I, Olsson Y, Reese TS (1970) The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci 10: 215–239
Brun A, Englund E (1986) A white matter disorder in dementia of the Alzheimer type; a pathoanatomical study. Ann Neurol 19: 253–262
de la Torre JC, Fortin T, Park GAS, Butler KS, Kozlowski P, Pappas BA, de Soccaraz H, Saunders JK, Richard MT (1992) Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats. Brain Res 582: 186–195
Eklöf B, Siesjö BK (1972) The effect of bilateral carotid artery ligation upon the blood flow and the energy state of the rat brain. Acta Physiol Scand 86: 155–165
Englund E, Brun A (1990) White matter changes in dementia of Alzheimer's type: the difference in vulnerability between cell compartments. Histopathology 16: 433–439
Feigin I, Popoff N (1963) Neuropathological changes late in cerebral edema: the relationship to trauma, hypertensive disease and Binswanger's encephalopathy. J Neuropathol Exp Neurol 22: 500–511
Fujishima M, Ishitsuka T, Nakatomi Y, Tamaki K, Omae T (1981) Changes in local cerebral blood flow following bilateral carotid occlusion in spontaneously hypertensive and normotensive rats. Stroke 12: 874–876
Galetta SL, Leahey A, Nichols CW, Raps EC (1991) Orbital ischemia, opthalmoparesis, and carotid dissection. J Clin Neuroophthalmol 11: 284–287
Gehrmann J, Bonnekoh P, Miyazawa T, Hossmann KA, Kreutzberg GW (1992) Immunocytochemical study of an early microglial activation in ischemia. J Cereb Blood Flow Metab 12: 257–269
Grafton ST, Sumid SM, Stimac GK, Alvord EC Jr, Shaw CM, Nochlin D (1991) Comparison of postmortem magnetic resonance imaging and neuropathologic findings in the cerebral white matter. Arch Neurol 48: 293–298
Gray F, Dubas F, Roulett E, Escourolle R (1985) Leukoencephalopathy in diffuse hemorrhagic amyloid angiopathy. Ann Neurol 18: 54–59
Hattori H, Takeda M, Kudo T, Nishimura T, Hashimoto S (1992) Cumulative white matter changes in the gerbil brain under chronic cerebral hypoperfusion. Acta Neuropathol 84: 437–442
Huang K, Wee L, Luo Y (1985) Binswanger's disease: progressive subcortical encephalopathy or multi-infarct dementia. Can J Neurol Sci 12: 88–94
Iwasaki Y, Ito S, Suzuki M, Nagahori T, Yamamoto T, Konno H (1989) Forebrain ischemia by temporal bilateral common carotid occlusion in normotensive rats. J Neurol Sci 90: 155–165
Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239: 57–69
Klatzo I, Piraux A, Laskowski EJ (1958) The relationship between edema, blood-brain-barrier and tissue elements in a local brain injury. J Neuropathol Exp Neurol 17: 548–564
Kudo T, Tada K, Takeda M, Nishimura T (1990) Learning impairment and microtubule-associated protein 2 decrease in gerbils under chronic cerebral hypoperfusion. Stroke 21: 423–428
Levine S, Klein M (1960) Ischemic infarction and swelling in the rat brain. A M A Arch Pathol 69: 544–553
Mabe H, Umemura S, Iwayama K, Takagi T, Nagai H (1981) Cerebral blood flow, EEG power spectrum, and histopathology in experimental cerebral ischemia. J Cereb Blood Flow Metab 1 [Suppl]: S241-S242
Morioka T, Kalehua AN, Streit WJ (1991) The microglial reaction in the rat dorsal hippocampus following transient cerebral ischemia. J Cereb Blood Flow Metab 11: 966–973
Morioka T, Kalehua AN, Streit WJ (1992) Progressive expression of immunomolecules on microglial cells in rat dorsal hippocampus following transient forebrain ischemia. Acta Neuropathol 83: 149–157
Ogata J, Fujishima M, Morimoto Y, Omae T (1976) Cerebral infarction following bilateral carotid artery ligation in normotensive and spontaneously hypertensive rats: a pathological study. Stroke 7: 54–60
Payan HM, Levine S, Strebel R (1965) Effects of cerebral ischemia in various strains of rats. Proc Soc Exp Biol Med 120: 208–209
Petit CK, Morgello S, Felix JC, 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
Shiokawa O, Sadoshima S, Kusuda K, Nishimura Y, Ibayashi S, Fujishima M (1986) Cerebral and cerebellar blood flow autoregulations in acutely induced cerebral ischemia in spontaneously hypertensive rats — Transtentorial remote effect. Stroke 17: 1309–1313
Slakter JS, Spertus AD, Weissmann SS, Henkind P (1984) An experimental model of carotid artery occlusive disease. Am J Opthalmol 97: 169–172
Takamatsu J, Hirano A, Levy D, Henkind P (1984) Experimental bilateral carotid artey occlusion: a study of the optic nerve in the rat. Neuropathol Appl Neurol 10: 423–428
Tomimoto H, Akiguchi I, Akiyama H, Kimura J, Yanagihara T (1993) T cell infiltration and expression of MHC class II antigen by macrophage/microglia in a heterogeneous group of leukoencephalopathy. Am J Pathol 143: 579–586
Yanagihara T, Yoshimine T, Morimoto K, Yamamoto K, Homburger HA (1985) Immunohistochemical investigation of cerebral ischemia in gerbils. J Neuropathol Exp Neurol 44: 204–215
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
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Wakita, H., Tomimoto, H., Akiguchi, I. et al. Glial activation and white matter changes in the rat brain induced by chronic cerebral hypoperfusion: an immunohistochemical study. Acta Neuropathol 87, 484–492 (1994). https://doi.org/10.1007/BF00294175
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DOI: https://doi.org/10.1007/BF00294175