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-betaapp) and myelin basic protein (MBP). Recruitment peak of neutrophils and macrophages occurred at 1 and 7 days post-nmda injection, respectively. Diffuse damaged axons (beta-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.
Subject(s)
Corpus Striatum/drug effects , Corpus Striatum/metabolism , Myelin Sheath/metabolism , N-Methylaspartate/pharmacology , Animals , Axons/metabolism , Excitatory Amino Acid Agonists/pharmacology , Gliosis , Immunohistochemistry/methods , Inflammation , Macrophages/metabolism , Male , Neutrophils/metabolism , Perfusion , Rats , Rats, WistarABSTRACT
Objetivo: revisar a literatura científica sobre degeneração da substância branca, incluindo lesão do cilindro axonal, da bainha de mielina e oligodendrócitos, enfatizando o papel deste evento patológico na perda tecidual e deficiências funcionais subjacentes às doenças neurodegenerativas agudas e crônicas. Método: revisão de literatura através de pesquisa bibliográfica na base de dados PUBMED/MEDLINE. Considerações Finais: o comprometimento patológico da substância branca é um mecanismo importante dafisiopatologia de doenças neurodegenerativas agudas e crônicas. Pesquisas translacionais nesta área devem ser realizadas para o desenvolvimento de novas abordagens terapêuticas para essas desordens neurais. Um objetivo importante destes estudos deve ser a proteção dos tratos de substância branca do sistema nervoso central humano, os quais podem degenerar durante doenças, incluindo trauma cerebral e medular, acidente vascular encefálico e esclerose múltipla.
Objective: review the literature on the white matter pathology, including axonal damage, myelin impairment and oligodendrocyte degeneration, emphasizing the importance of this pathological event on the underlying functional deficits following neurodegenerative diseases. Method: bibliography search using PUBME/MEDLlNE databases. Final considerations: the pathological impairment of white matter is an important mechanism underlying the pathophysiology of both acute and chronic neurodegenerative disorders. Translational researches should beaccomplished for the development of new therapeutic approaches for human brain disorders. An important aim of these investigations must be the protection of the human white matter tracts, which are damaged following neural disorders, including brain and spinal cord trauma, stroke and multiple sclerosis.
