Increased levels of proinflammatory cytokines in the aged rat brain attenuate injury-induced cytokine response after excitotoxic damage
Autor: | M. M. Castillo-Ruiz, Oscar Campuzano, Bernardo Castellano, Laia Acarin, Berta González |
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Rok vydání: | 2009 |
Předmět: |
Male
medicine.medical_specialty Pathology Aging N-Methylaspartate Time Factors medicine.medical_treatment Interleukin-1beta Striatum Proinflammatory cytokine Lesion Cellular and Molecular Neuroscience Internal medicine medicine Animals Rats Wistar Interleukin 6 Cerebral Cortex Neurons biology Microglia Interleukin-6 Tumor Necrosis Factor-alpha Macrophages Brain Corpus Striatum Rats medicine.anatomical_structure Endocrinology Cytokine Astrocytes Brain Injuries biology.protein Tumor necrosis factor alpha medicine.symptom Astrocyte |
Zdroj: | Journal of neuroscience research. 87(11) |
ISSN: | 1097-4547 |
Popis: | In order to evaluate proinflammatory cytokine levels and their producing cell types in the control aged rat brain and after acute excitotoxic damage, both adult and aged male Wistar rats were injected with N-methyl-D-aspartate in the striatum. At different survival times between 6 hr and 7 days after lesioning, interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were analyzed by enzyme-linked immunosorbent assay and by double immunofluorescence of cryostat sections by using cell-specific markers. Basal cytokine expression was attributed to astrocytes and was increased in the normal aged brain showing region specificity: TNF-alpha and IL-6 displayed age-dependent higher levels in the aged cortex, and IL-1beta and IL-6 in the aged striatum. After excitotoxic striatal damage, notable age-dependent differences in cytokine induction in the aged vs. the adult were seen. The adult injured striatum exhibited a rapid induction of all cytokines analyzed, but the aged injured striatum showed a weak induction of cytokine expression: IL-1beta showed no injury-induced changes at any time, TNF-alpha presented a late induction at 5 days after lesioning, and IL-6 was only induced at 6 hr after lesioning. At both ages, in the lesion core, all cytokines were early expressed by neurons and astrocytes, and by microglia/macrophages later on. However, in the adjacent lesion border, cytokines were found in reactive astrocytes. This study highlights the particular inflammatory response of the aged brain and suggests an important role of increased basal levels of proinflammatory cytokines in the reduced ability to induce their expression after damage. |
Databáze: | OpenAIRE |
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