Association between inflammation and nigral neuronal damage following striatal excitotoxic lesion. 2004

F Block, and M Loos, and C Frohn, and M Schwarz
Department of Neurology, University of Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany. fblock@ukaachen.de

We examined the expression of TNF-alpha within the substantia nigra pars reticulata (SNR) following intrastriatal injection of quinolinic acid (QA) and studied the effect of rolipram, a TNF-alpha-inhibitor, on the secondary neuronal damage. QA (240 nmol in 1 microl) was injected stereotactically into the striatum of male Wistar rats. After survival of 1, 3 or 10 days, the animals were sacrificed and immunohistochemical staining with an antibody against TNF-alpha was performed. From day 1 to day 10 after striatal QA injection TNF-alpha positive cells were observed within ipsilateral substantia nigra which were neither present on the contralateral side nor in sham-operated controls. Double labeling with antibodies against TNF-alpha and NeuN, keratan sulfate proteoglycan or GFAP displayed a good overlap between TNF-alpha and NeuN, which suggests that TNF-alpha positive cells are neurons. For the pharmacological approach, three groups of QA rats were treated intraperitoneally with either solvent (n=5), the NMDA receptor antagonist MK 801 (4 mg/kg, n=6) or the TNF-alpha inhibitor rolipram (0.3 mg/kg, n=6), which was started 24 h after QA-injection and continued with daily applications for 14 days. The amount of striatal damage did not differ between the three groups. The number of intact neurons within the ipsilateral substantia nigra of the solvent treated group was reduced by approximately 30% compared to the contralateral side. Both MK 801 and rolipram ameliorated this secondary damage and reduced the number of TNF-alpha positive cells. The observed association between expression of TNF-alpha and secondary neuronal damage within the substantia nigra induced by intrastriatal QA application might hint towards an involvement of this cytokine in transneuronal degeneration.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007632 Keratan Sulfate A sulfated mucopolysaccharide initially isolated from bovine cornea. At least two types are known. Type I, found mostly in the cornea, contains D-galactose and D-glucosamine-6-O-sulfate as the repeating unit; type II, found in skeletal tissues, contains D-galactose and D-galactosamine-6-O-sulfate as the repeating unit. Keratosulfate,Sulfate, Keratan
D007839 Functional Laterality Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. Ambidexterity,Behavioral Laterality,Handedness,Laterality of Motor Control,Mirror Writing,Laterality, Behavioral,Laterality, Functional,Mirror Writings,Motor Control Laterality,Writing, Mirror,Writings, Mirror
D008297 Male Males
D010726 Phosphodiesterase Inhibitors Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. Phosphodiesterase Antagonists,Phosphodiesterase Inhibitor,Phosphoric Diester Hydrolase Inhibitors,Antiphosphodiesterases,Inhibitor, Phosphodiesterase
D010751 Phosphopyruvate Hydratase A hydro-lyase that catalyzes the dehydration of 2-phosphoglycerate to form PHOSPHOENOLPYRUVATE. Several different isoforms of this enzyme exist, each with its own tissue specificity. Enolase,Neuron-Specific Enolase,2-Phospho-D-Glycerate Hydro-Lyase,2-Phospho-D-Glycerate Hydrolase,2-Phosphoglycerate Dehydratase,Enolase 2,Enolase 3,Muscle-Specific Enolase,Nervous System-Specific Enolase,Non-Neuronal Enolase,alpha-Enolase,beta-Enolase,gamma-Enolase,2 Phospho D Glycerate Hydro Lyase,2 Phospho D Glycerate Hydrolase,2 Phosphoglycerate Dehydratase,Dehydratase, 2-Phosphoglycerate,Enolase, Muscle-Specific,Enolase, Nervous System-Specific,Enolase, Neuron-Specific,Enolase, Non-Neuronal,Hydratase, Phosphopyruvate,Hydro-Lyase, 2-Phospho-D-Glycerate,Muscle Specific Enolase,Nervous System Specific Enolase,Neuron Specific Enolase,Non Neuronal Enolase,System-Specific Enolase, Nervous,alpha Enolase,beta Enolase,gamma Enolase
D011508 Chondroitin Sulfate Proteoglycans Proteoglycans consisting of proteins linked to one or more CHONDROITIN SULFATE-containing oligosaccharide chains. Proteochondroitin Sulfates,Chondroitin Sulfate Proteoglycan,Proteochondroitin Sulfate,Proteoglycan, Chondroitin Sulfate,Proteoglycans, Chondroitin Sulfate,Sulfate Proteoglycan, Chondroitin,Sulfate Proteoglycans, Chondroitin
D001927 Brain Diseases Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM. Intracranial Central Nervous System Disorders,Brain Disorders,CNS Disorders, Intracranial,Central Nervous System Disorders, Intracranial,Central Nervous System Intracranial Disorders,Encephalon Diseases,Encephalopathy,Intracranial CNS Disorders,Brain Disease,Brain Disorder,CNS Disorder, Intracranial,Encephalon Disease,Encephalopathies,Intracranial CNS Disorder
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell

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