Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Neuroscience |
| Vol/bind | 102 |
| Udgave nummer | 4 |
| Sider (fra-til) | 805-18 |
| Antal sider | 13 |
| ISSN | 0306-4522 |
| Status | Udgivet - 2001 |
Bibliografisk note
Keywords: Animals; Apoptosis; Blood-Brain Barrier; Encephalitis; Epilepsy; Excitatory Amino Acid Agonists; Gene Expression; Gliosis; Hippocampus; In Situ Nick-End Labeling; Interleukin-6; Kainic Acid; Macrophages; Metallothionein; Mice; Mice, Knockout; Microglia; Nerve Degeneration; Oxidative Stress; Seizures; Superoxide DismutaseCitationsformater
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I: Neuroscience, Bind 102, Nr. 4, 2001, s. 805-18.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures
AU - Penkowa, M
AU - Molinero, A
AU - Carrasco, J
AU - Hidalgo, J
N1 - Keywords: Animals; Apoptosis; Blood-Brain Barrier; Encephalitis; Epilepsy; Excitatory Amino Acid Agonists; Gene Expression; Gliosis; Hippocampus; In Situ Nick-End Labeling; Interleukin-6; Kainic Acid; Macrophages; Metallothionein; Mice; Mice, Knockout; Microglia; Nerve Degeneration; Oxidative Stress; Seizures; Superoxide Dismutase
PY - 2001
Y1 - 2001
N2 - The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice, and caused a significant mortality (62%) only in the latter mice, indicating that interleukin-6 deficiency increased the susceptibility to kainic acid-induced brain damage. To compare the histopathological damage caused to the brain, control and interleukin-6 null mice were administered 8.75mg/kg kainic acid and were killed six days later. Morphological damage to the hippocampal field CA1-CA3 was seen after kainic acid treatment. Reactive astrogliosis and microgliosis were prominent in kainic acid-injected normal mice hippocampus, and clear signs of increased oxidative stress were evident. Thus, the immunoreactivity for inducible nitric oxide synthase, peroxynitrite-induced nitration of proteins and byproducts of fatty acid peroxidation were dramatically increased, as was that for metallothionein I+II, Mn-superoxide dismutase and Cu/Zn-superoxide dismutase. In accordance, a significant neuronal apoptosis was caused by kainic acid, as revealed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and interleukin-1beta converting enzyme/Caspase-1 stainings. In kainic acid-injected interleukin-6 null mice, reactive astrogliosis and microgliosis were reduced, while morphological hippocampal damage, oxidative stress and apoptotic neuronal death were increased. Since metallothionein-I+II levels were lower, and those of inducible nitric oxide synthase higher, these concomitant changes are likely to contribute to the observed increased oxidative stress and neuronal death in the interleukin-6 null mice. The present results demonstrate that interleukin-6 deficiency increases neuronal injury and impairs the inflammatory response after kainic acid-induced seizures.
AB - The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice, and caused a significant mortality (62%) only in the latter mice, indicating that interleukin-6 deficiency increased the susceptibility to kainic acid-induced brain damage. To compare the histopathological damage caused to the brain, control and interleukin-6 null mice were administered 8.75mg/kg kainic acid and were killed six days later. Morphological damage to the hippocampal field CA1-CA3 was seen after kainic acid treatment. Reactive astrogliosis and microgliosis were prominent in kainic acid-injected normal mice hippocampus, and clear signs of increased oxidative stress were evident. Thus, the immunoreactivity for inducible nitric oxide synthase, peroxynitrite-induced nitration of proteins and byproducts of fatty acid peroxidation were dramatically increased, as was that for metallothionein I+II, Mn-superoxide dismutase and Cu/Zn-superoxide dismutase. In accordance, a significant neuronal apoptosis was caused by kainic acid, as revealed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and interleukin-1beta converting enzyme/Caspase-1 stainings. In kainic acid-injected interleukin-6 null mice, reactive astrogliosis and microgliosis were reduced, while morphological hippocampal damage, oxidative stress and apoptotic neuronal death were increased. Since metallothionein-I+II levels were lower, and those of inducible nitric oxide synthase higher, these concomitant changes are likely to contribute to the observed increased oxidative stress and neuronal death in the interleukin-6 null mice. The present results demonstrate that interleukin-6 deficiency increases neuronal injury and impairs the inflammatory response after kainic acid-induced seizures.
M3 - Journal article
C2 - 11182244
SN - 0306-4522
VL - 102
SP - 805
EP - 818
JO - Neuroscience
JF - Neuroscience
IS - 4
ER -