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Diffuse Axonal Damage, Myelin Impairment, Astrocytosis and Inflammatory Response Following Microinjections of NMDA into The Rat Striatum

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Abstract

White matter damage and inflammatory response are important secondary outcomes after acute neural disorders. Nevertheless, a few studies addressed the temporal outcomes of these pathological events using non-traumatic models of acute brain injury. In the present study, we describe acute inflammatory response and white matter neuropathology between 1 and 7 days after acute excitotoxic striatal damage. Twenty micrometer sections were stained by hematoxylin and eosin technique for gross histopathological analysis and immunolabed for neutrophils (anti-mbs-1), activated macrophages/microglia (anti-ed1), astrocytes (anti-gfap), damaged axons (anti-βapp) and myelin basic protein (MBP). Recruitment peak of neutrophils and macrophages occurred at 1 and 7 days post-nmda injection, respectively. Diffuse damaged axons (β-app + end-bulbs) were apparent at 7 days, concomitant with progressive myelin impairment and astrocytosis. Further studies using electron microscopy and blockers of inflammatory response and glutamatergic receptors should be performed to confirm and address the mechanisms of white matter damage following an excitotoxic lesion.

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Acknowledgments

This work was supported by FUNTEC/SECTAM-PARÁ (grant 1033) and CNPQ-Brazil. The authors wish to thank Professor Victor Hugh Perry (CNS Inflammation Group, Southampton University) for the provision of the MBS-1 antibody, FADESP/UFPA for financial support and Marco Aurélio de Moura Freire for contribution on the immunocytochemical studies.

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Authors and Affiliations

  1. Laboratory of Experimental Neuroprotection and Neuroregeneration, Department of Morphology, Biological Sciences Center, Federal University of Pará, Rua Augusto Corrêa N. 1. Campus do Guamá, CEP: 66075-900, Belém-Pará, Brazil

    Rafael R. Lima, Joanilson Guimaraes-Silva, Jorge L. Oliveira, Ana Maria R. Costa, Renata D. Souza-Rodrigues, Claudia D. Dos Santos & Walace Gomes-Leal

  2. Functional Neuroanatomy, Department of Morphology, Biological Sciences Center, Federal University of Pará, Rua Augusto Corrêa N. 1. Campus do Guamá, CEP: 66075-900, Belém-Pará, Brazil

    Cristovam W. Picanço-Diniz

  3. Lund Strategic Research Center for Stem Cell Biology and Cell Therapy and Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84, Lund, Sweden

    Walace Gomes-Leal

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  1. Rafael R. Lima
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Correspondence to Walace Gomes-Leal.

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Lima, R.R., Guimaraes-Silva, J., Oliveira, J.L. et al. Diffuse Axonal Damage, Myelin Impairment, Astrocytosis and Inflammatory Response Following Microinjections of NMDA into The Rat Striatum. Inflammation 31, 24–35 (2008). https://doi.org/10.1007/s10753-007-9046-y

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