Contribution of microglia/macrophages to expansion of infarction and response of oligodendrocytes after focal cerebral ischemia in rats
Abstract
BACKGROUND AND PURPOSE: The purpose of this study was (1) to examine the contribution of microglia and macrophages with their interleukin-1beta production and (2) to assess the vulnerability and response of oligodendrocytes in cerebral infarction. METHODS: Male Wistar rats were subjected to permanent occlusion of the left middle cerebral artery. Expansion of ischemic infarction and response of oligodendrocytes were investigated together with accumulation of inflammatory cells, production of interleukin-1beta, and disruption of the blood-brain barrier. Apoptotic cell death was inferred from fragmented DNA and the expression of proapoptotic Bax protein. RESULTS: During expansion of infarction, amoeboid microglia and extravasation of serum albumin were observed not only in the infarcted area but also in the adjacent surviving area, whereas macrophages accumulated along the boundary and granulocytes migrated into the center of the infarction. Both amoeboid microglia and macrophages produced interleukin-1beta, an inflammatory cytokine, during an early ischemic period. Furthermore, macrophages within the infarcted tissue expressed Bax protein and subsequently showed fragmented nuclear DNA. Oligodendrocytes were detected in the infarcted area even after 24 hours following middle cerebral artery occlusion, but they subsequently developed fragmented DNA. A week after onset of ischemia, oligodendrocytes were found to be accumulated in the intact area bordered with the infarct together with reactive astrocytes. CONCLUSIONS: Our results suggest the importance of amoeboid microglia, macrophages, and their interleukin-1beta production in gradual expansion of cerebral infarction. Resident oligodendrocytes may be resistant to ischemic insults, and oligodendrocytes accumulated at the border of the infarction may participate in tissue repair after cerebral infarction.
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PMN infiltration as well as amoeboid microglia along the edges of the stroke infarct may be responsible for expansion of the penumbra region, which occurs from 16 h onward after MCAo followed by reperfusion.
“Moreover, PMN in-filtration as well as amoeboid microglia along the edges of the stroke infarct may be responsible for expansion of the penumbra region, which occurs from 16 h onward after MCAo followed by reperfusion (Mabuchi et al., 2000).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Mabuchi et al., 2000
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Cites
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S. A. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.493 · Cited by 9,444 · see citing works
Reversible middle cerebral artery occlusion without craniectomy in rats.
Longa, E. Z., Weinstein, P. R., Carlson, S., & Cummins, R. (1989) · Stroke · doi:10.1161/01.str.20.1.84 · Cited by 7,463 · see citing works
Thresholds in cerebral ischemia - the ischemic penumbra.
Astrup, J., Siesjö, B. K., & Symon, L. (1981) · Stroke · doi:10.1161/01.str.12.6.723 · Cited by 2,820 · see citing works
Viability thresholds and the penumbra of focal ischemia
Hossmann, K. (1994) · Annals of Neurology · doi:10.1002/ana.410360404 · Cited by 1,370 · see citing works
Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys
Crowe, M. J., Bresnahan, J. C., Shuman, S. L., Masters, J. N., & Beattie, M. S. (1997) · Nature Medicine · doi:10.1038/nm0197-73 · Cited by 1,153 · see citing works
Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice
Eglitis, M. A., & Mezey, É. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4080 · Cited by 1,015 · see citing works
Experimental studies of ischemic brain edema
Koizumi, J.-I., Yoshida, Y., Nakazawa, T., & Ooneda, G. (1986) · Nosotchu · doi:10.3995/jstroke.8.1 · Cited by 996 · see citing works
Inflammation and glial responses in ischemic brain lesions
Stoll, G. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00034-3 · Cited by 794 · see citing works
Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide.
Merrill, J. E., Ignarro, L. J., Sherman, M. P., Melinek, J., & Lane, T. E. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.4.2132 · Cited by 782 · see citing works
del Zoppo, G. J., Schmid‐Schönbein, G. W., Mori, E., Copeland, B. R., & Chang, C.-H. (1991) · Stroke · doi:10.1161/01.str.22.10.1276 · Cited by 764 · see citing works
The role of microglia and macrophages in the pathophysiology of the CNS
Stollg, G., & Jander, S. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00083-5 · Cited by 683 · see citing works
Kochanek, P. M., & Hallenbeck, J. M. (1992) · Stroke · doi:10.1161/01.str.23.9.1367 · Cited by 615 · see citing works
Cerebral White Matter Is Highly Vulnerable to Ischemia
Pantoni, L., García, J. H., & Gutierrez, J. A. (1996) · Stroke · doi:10.1161/01.str.27.9.1641 · Cited by 610 · see citing works
Astrocyte Responses to CNS Injury
Norenberg, M. D. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199405000-00001 · Cited by 589 · see citing works
Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat).
García, J. H., Liu, K. F., Yoshida, Y., Lian, J., Chen, S., & del Zoppo, G. J. (1994) · PubMed Central · Cited by 496 · see citing works
Lectin binding by resting and reactive microglia
Streit, W. J., & Kreutzberg, G. W. (1987) · Journal of Neurocytology · doi:10.1007/bf01795308 · Cited by 496 · see citing works
Matsuo, Y., Onodera, H., Shiga, Y., Nakamura, M., Ninomiya, M., Kihara, T., & Kogure, K. (1994) · Stroke · doi:10.1161/01.str.25.7.1469 · Cited by 485 · see citing works
Loddick, S. A., & Rothwell, N. J. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199609000-00017 · Cited by 465 · see citing works
Chemokine and Inflammatory Cell Response to Hypoxia-Ischemia in Immature Rats
Bona, E., Andersson, A.-L., Blomgren, K., Gilland, E., Puka‐Sundvall, M., Gustafson, K., & Hagberg, H. (1999) · Pediatric Research · doi:10.1203/00006450-199904010-00008 · Cited by 338 · see citing works
Gregersen, R., Lambertsen, K. L., & Finsen, B. R. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200001000-00009 · Cited by 314 · see citing works
Kitagawa, K., Matsumoto, M., Niinobe, M., Mikoshiba, K., Hata, R., Ueda, H., Handa, N., Fukunaga, R., Isaka, Y., Kimura, K., et al. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90383-7 · Cited by 299 · see citing works
Self-citationCharacterization of microglial reaction after middle cerebral artery occlusion in rat brain
Morioka, T., Kalehua, A. N., & Streit, W. J. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903270110 · Cited by 272 · see citing works
Wang, X.-K., Yue, T., Barone, F., White, R. F., Gagnon, R., & Feuerstein, G. (1994) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815404 · Cited by 262 · see citing works
Back, T., Ginsberg, M. D., Dietrich, W. D., & Watson, B. D. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199603000-00004 · Cited by 248 · see citing works
Davies, C. A., Loddick, S. A., Toulmond, S., Stroemer, R. P., Hunt, J., & Rothwell, N. J. (1999) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199901000-00010 · Cited by 236 · see citing works
Bcl-2 Protects Macrophages from Nitric Oxide-induced Apoptosis
Meβmer, U. K., Reed, J. C., & Brüne, B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.33.20192 · Cited by 220 · see citing works
The ischemic penumbra, injury thresholds, and the therapeutic window for acute stroke
Ginsberg, M. D., & Pulsinelli, W. A. (1994) · Annals of Neurology · doi:10.1002/ana.410360402 · Cited by 212 · see citing works
Monocyte chemoattractant protein-1 messenger RNA expression in rat ischemic cortex.
Wang, X.-K., Yue, T., Barone, F., & Feuerstein, G. (1995) · Stroke · doi:10.1161/01.str.26.4.661 · Cited by 203 · see citing works
Glutamate‐Mediated Injury in Focal Cerebral Ischemia: The Excitotoxin Hypothesis Revised
Hossmann, K. (1994) · Brain Pathology · doi:10.1111/j.1750-3639.1994.tb00808.x · Cited by 199 · see citing works
Morphine Enhances Macrophage Apoptosis
Singhal, P. C., Sharma, P., Kapasi, A. A., et al. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.4.1886 · Cited by 197 · see citing works
Donor-Derived Cells in the Central Nervous System of Twitcher Mice After Bone Marrow Transplantation
Hoogerbrugge, P. M., Suzuki, K., Suzuki, K., Poorthuis, B. J. H. M., Kobayashi, T., Wagemaker, G., & van Bekkum, D. W. (1988) · Science · doi:10.1126/science.3278379 · Cited by 182 · see citing works
Ellison, J. A., Velier, J. J., Spera, P. A., Jonak, Z., Wang, X., Barone, F. C., & Feuerstein, G. (1998) · Stroke · doi:10.1161/01.str.29.8.1698 · Cited by 170 · see citing works
Raivich, G., Moreno-Flores, M. T., Möller, J. C., & Kreutzberg, G. W. (1994) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1994.tb00552.x · Cited by 169 · see citing works
García, J. H., Liu, K. F., Yoshida, Y., Chen, S., & Lian, J. (1994) · PubMed Central · Cited by 164 · see citing works
Abumiya, T., Lucero, J. D., Heo, J. H., Tagaya, M., Koziol, J. A., Copeland, B. R., & del Zoppo, G. J. (1999) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199909000-00012 · Cited by 156 · see citing works
Gehrmann, J., & Banati, R. B. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199509000-00010 · Cited by 147 · see citing works
Yamagami, S., Tamura, M., Hayashi, M., Endo, N., Tanabe, H., Katsuura, Y., & Komoriya, K. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.65.6.744 · Cited by 141 · see citing works
Kempf, S. C., Page, L. R., & Pires, A. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19970929)386:3 · Cited by 130 · see citing works
Ischemic damage and subsequent proliferation of oligodendrocytes in focal cerebral ischemia
Mandai, K., Matsumoto, M., Kitagawa, K., Matsushita, K., Ohtsuki, T., Mabuchi, T., Colman, D., Kamada, T., & Yanagihara, T. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00517-9 · Cited by 118 · see citing works
Self-citationProduction of colony‐stimulating factor‐1 (CSF‐1) by mouse astroglia in vitro
Hao, C., Guilbert, L. J., & FEDOROFF, S. (1990) · Journal of Neuroscience Research · doi:10.1002/jnr.490270310 · Cited by 114 · see citing works
Panek, R. B., & Benveniste, E. N. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.6.2846 · Cited by 113 · see citing works
DNA Scission After Focal Brain Ischemia
Tagaya, M., Liu, K.-F., Copeland, B. R., Seiffert, D., Engler, R. L., García, J. H., & del Zoppo, G. J. (1997) · Stroke · doi:10.1161/01.str.28.6.1245 · Cited by 111 · see citing works
Possible involvement of interleukin-1 in ischemic brain edema formation
Yamasaki, Y., SUZUKI, T. A., Yamaya, H., Matsuura, N., Onodera, H., & Kogure, K. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90616-f · Cited by 105 · see citing works
Immunohistochemical Investigation of Cerebral Ischemia in Gerbils
Yanagihara, T., Yoshimine, T., Morimoto, K., Yamamoto, K., & Homburger, H. A. (1985) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198503000-00009 · Cited by 102 · see citing works
Self-citationThe distribution of myelin basic protein mRNAs within myelinating oligodendrocytes
Brophy, P., Boccaccio, G. L., & Colman, D. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90196-s · Cited by 81 · see citing works
Brain Injury in the Premature Infant - Current Concepts
Volpe, J. J. (1994) · Preventive Medicine · doi:10.1006/pmed.1994.1106 · Cited by 48 · see citing works
Neurons Promote Macrophage Proliferation by Producing Transforming Growth Factor-β2
Dobbertin, A., Schmid, P., Gelman, M., Glowinski, J., & Mallat, M. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-14-05305.1997 · Cited by 43 · see citing works
Expression of Kv1.5 K channels in activated microglia in vivo
Jou, I., Pyo, H., Chung, S., Jung, S. Y., Gwag, B. J., & Joe, E.-H. (1998) · Glia · doi:10.1002/(sici)1098-1136(199812)24:4 · Cited by 43 · see citing works
Rodriguez, M., Prayoonwiwat, N., Howe, C. L., & Sanborn, K. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199403000-00004 · Cited by 42 · see citing works
Chapter 26 Neurotransmitters and cytokines in CNS pathology
Mitrovic, B., Martin, F. C., Charles, A. C., Ignarro, L. J., Anton, P. A., Shanahan, F., & Merrill, J. E. (1994) · Progress in brain research · doi:10.1016/s0079-6123(08)61146-2 · Cited by 29 · see citing works
Evolution of Microcirculatory Disturbances after Permanent Middle Cerebral Artery Occlusion in Rats
Vogel, J., Hermes, A., & Kuschinsky, W. (1999) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199912000-00005 · Cited by 16 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- Garcia JH, Yoshida Y, Chen H, Li Y, Zhang ZG, Lian J, Chen S, Chopp M. Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am J Pathol. 1993;1993:142:623-635.
- Iadecola C, Zhang F, Xu X. Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage. Am J Physiol. 1995;268: R286 -R292.
- Bruck W, Schmied M, Suchanek G, Bruck Y, Breitshopf H, Poser S, Piddlesden S, Lassmann H. Oligodendrocytes in the early course of multiple sclerosis. Ann Neurol. 1994;36:65-73.
- Mitrovic B, Martin FC, Charled AC, Ignarro LJ, Anton PA, Shanahan F, Merrill JE. Neurotransmitters and cytokines in CNS pathology. Prog Brain Res. 1994;103:319 -330.
- Brierley JB, Graham DI. Hypoxia and vascular disorders of the central nervous system. In: Adams JH, Corsellis JAN, Duchen LW, eds. Green- field's Neuropathology. 4th ed. London, England: Edward Arnold; 1984: 125-207.
- Lehrmann E, Christensen T, Zimmer J, Diemer NH, Finsen B. Microglial and macrophage reactions mark progressive changes and define the penumbra in the rat neocortex and striatum after transient middle cerebral artery occlusion. J Comp Neurol. 1997;386:461-476.
- del Zoppo GJ, Schmid-Scho ¨nbein GW, Mori E, Copeland BR, Chang C-M. Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke. 1991;22:1276 -1283.
- Wang XK, Yue T-L, Barone FC, White RF, Gagnon RC, Feuerstein GZ. Concommitant cortical expression of TNF-a ´and IL-1a ˆmRNA following transient focal ischemia. Mol Chem Neuropathol. 1994;23:103-114.
- Lehrmann E, Kiefer R, Christensen T, Tovka KV, Zimmer J, Diemer NH, Hartung H, Finsen B. Microglia and macrophages are major sources of locally produced transforming growth factor-a ˆ1 after transient middle cerebral artery occlusion in rats. Glia. 1998;24:437-448.
Cited by
Sorted by citations
Marcheselli, V. L., Hong, S., Lukiw, W. J., Tian, X. H., Gronert, K., Musto, A., Hardy, M., Gimenez, J. M., Chiang, N., Serhan, C. N., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305841200 · Cited by 802 · see citing works
Eljaschewitsch, E., Witting, A., Mawrin, C., Lee, T., Schmidt, P. M., Wolf, S., Hoertnagl, H., Raine, C. S., Schneider-Stock, R., Nitsch, R., et al. (2006) · Neuron · doi:10.1016/j.neuron.2005.11.027 · Cited by 445 · see citing works
Oligodendrocytes and Ischemic Brain Injury
Dewar, D., Underhill, S. M., & Goldberg, M. P. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000053472.41007.f9 · Cited by 335 · see citing works
Schilling, M., Besselmann, M., Müller, M., Strecker, J. K., Ringelstein, E. B., & Kiefer, R. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2005.08.004 · Cited by 288 · see citing works
Inflammation and the neurovascular unit in the setting of focal cerebral ischemia
del Zoppo, G. J. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2008.08.028 · Cited by 243 · see citing works
Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury
Soriano, S. G., Amaravadi, L. S., Wang, Y. F., Zhou, H., Yu, G. X., Tonra, J. R., Fairchild-Huntress, V., Fang, Q., Dunmore, J. H., Huszar, D., et al. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00033-4 · Cited by 222 · see citing works
Rueger, M. A., Keuters, M. H., Walberer, M., Braun, R., Klein, R., Sparing, R., Fink, G. R., Graf, R., & Schroeter, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043776 · Cited by 151 · see citing works
Bazan, N. G. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.09.003 · Cited by 148 · see citing works
Miyamoto, N., Tanaka, R., Shimura, H., Watanabe, T., Mori, H., Onodera, M., Mochizuki, H., Hattori, N., & Urabe, T. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.210 · Cited by 86 · see citing works
Ohk, T. G., Yoo, K.-Y., Park, S. M., Shin, B. N., Kim, I. H., Park, J. H., Ahn, H. C., Lee, Y. J., Kim, M. J., Kim, T. Y., et al. (2012) · Neurochemical Research · doi:10.1007/s11064-011-0678-9 · Cited by 29 · see citing works
- Authors
- Mabuchi, T., Kitagawa, K., Ohtsuki, T., Kuwabara, K., Yagita, Y., Yanagihara, T., Hori, M., & Matsumoto, M.
- Affiliations
- The University of Osaka (JP)
- Venue
- Stroke
- Published
- 2000-07
- Volume
- 31
- Issue
- 7
- Pages
- 1735-1743
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- OpenAlex
- W2146198846
- Cited by
- 280
- References
- 51
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 9 · 2016: 11 · 2015: 8 · 2014: 17 · 2013: 13 · 2012: 28
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, macrophages, focal cerebral ischemia, oligodendrocytes, IL-1β, blood-brain barrier disruption, Bax, apoptosis, reactive astrocytes, middle cerebral artery occlusion, tissue repair, neuroinflammation
- MeSH terms
- Animals, Brain Ischemia, Interleukin-1, Macrophages, Male, Oligodendroglia, RNA, Messenger, Rats, Wistar, Apoptosis, In Situ Hybridization, Microglia, Myelin Proteolipid Protein, Infarction, Middle Cerebral Artery, In Situ Nick-End Labeling, Rats, DNA Fragmentation
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