Rolipram reduces excitotoxic neuronal damage.
Proinflammatory cytokines are supposed to be involved in the pathophysiology of neuronal damage following excitotoxic lesions. We examined the effect of rolipram, a TNF-alpha-inhibitor, on excitotoxic neuronal damage. Quinolinic acid (240 nmol in 1 microl) was injected stereotactically into the striatum of male Wistar rats. Four groups of QA rats were treated i.p. with solvent, MK-801 (4 mg/kg) or rolipram (0.3 mg/kg) which was started either 6 or 24 h after QA injection and continued with daily applications for 14 days. QA injection induced neuronal damage which affected 93% of the striatal area. MK-801 reduced this damage to 12% of the striatal area. Treatment with rolipram when started at 6 h after QA injection resulted in neuronal damage amounting to 60%; the result after starting at 24 h was not different from solvent (91%). The present results demonstrate that rolipram reduces neuronal damage induced by intrastriatal QA application.
Block
F
F
Department of Neurology RWTH Aachen, Germany.
Schmidt
W
W
Nolden-Koch
M
M
Schwarz
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002452:Cell Count; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D014409:Tumor Necrosis Factor-alpha; D016291:Dizocilpine Maleate; D017378:Quinolinic Acid; D020889:Rolipram