Association between inflammation and nigral neuronal damage following striatal excitotoxic lesion.
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.
Block
F
F
Department of Neurology, University of Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany. fblock@ukaachen.de
Loos
M
M
Frohn
C
C
Schwarz
M
M
D000818:Animals; D001927:Brain Diseases / Q000378:metabolism / Q000503:physiopathology*; D002452:Cell Count; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003342:Corpus Striatum / Q000293:injuries / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism; D007632:Keratan Sulfate / Q000378:metabolism; D000071234:Lumican; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D011508:Chondroitin Sulfate Proteoglycans; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; C000604308:Lum protein, rat; D000071234:Lumican; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016291:Dizocilpine Maleate; D007632:Keratan Sulfate; D010751:Phosphopyruvate Hydratase; D017378:Quinolinic Acid; D020889:Rolipram