Association between inflammation and nigral neuronal damage following striatal excitotoxic lesion

• Published in: Brain research Vol. 998; no. 1; pp. 29 - 35
• Main Authors: Block, F., Loos, M., Frohn, C., Schwarz, M.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 13.02.2004; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Brain Diseases - metabolism; Brain Diseases - physiopathology; Cell Count; Central nervous system; Chondroitin Sulfate Proteoglycans - metabolism; Corpus Striatum - injuries; Corpus Striatum - physiopathology; Dizocilpine Maleate - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Functional Laterality; Fundamental and applied biological sciences. Psychology; Glial Fibrillary Acidic Protein - metabolism; Immunohistochemistry - methods; Inflammation - chemically induced; Inflammation - etiology; Inflammation - metabolism; Keratan Sulfate - metabolism; Lumican; Male; Phosphodiesterase Inhibitors - pharmacology; Phosphopyruvate Hydratase - metabolism; Quinolinic Acid - toxicity; Rats; Rats, Wistar; Rolipram; Rolipram - pharmacology; Substantia nigra; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - physiopathology; Time Factors; TNF-α; Transneuronal degeneration; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: nervous system and sense organs; Disorders of the nervous system; Rolipram; TNF-α; Substantia nigra; Transneuronal degeneration; Rat; Cytokine; Rodentia; Central nervous system; Basal ganglion; Corpus striatum; Inflammation; Encephalon; Vertebrata; Mammalia; Locus niger; Degeneration; Lesion; Tumor necrosis factor α
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2003.10.058

We examined the expression of TNF-α within the substantia nigra pars reticulata (SNR) following intrastriatal injection of quinolinic acid (QA) and studied the effect of rolipram, a TNF-α-inhibitor, on the secondary neuronal damage. QA (240 nmol in 1 μl) 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-α was performed. From day 1 to day 10 after striatal QA injection TNF-α 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-α and NeuN, keratan sulfate proteoglycan or GFAP displayed a good overlap between TNF-α and NeuN, which suggests that TNF-α 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-α 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-α positive cells. The observed association between expression of TNF-α and secondary neuronal damage within the substantia nigra induced by intrastriatal QA application might hint towards an involvement of this cytokine in transneuronal degeneration.