Intrastriatal injections of quinolinic acid or kainic acid: differential patterns of cell survival and the effects of data analysis on outcome.
There is controversy about the extent to which lesions of the rat striatum with excitatory amino acids mimic the cellular pathology seen in Huntington's Disease (HD). We sought to resolve this debate by determining with cell counts in adjacent sections the patterns of survival of medium spiny and aspiny striatal neurons using enkephalin immunohistochemistry and NADPH-diaphorase histochemistry as markers of these cell populations, respectively. Results showed that 2 weeks after quinolinic acid lesions, cell loss was qualitatively similar for the two cell groups. However, by varying the size of the sampling area for quantitative analyses and its distance from the lesion zone, the outcome of the statistical analyses varied enormously. Thus, a relative sparing of NADPH-diaphorase-labeled cells compared to enkephalin-labeled cells could be detected quantitatively in transition areas bordering the lesion under some but not all analytical conditions. Kainic acid lesions depleted both cell populations similarly, except in regions of transition farthest from the lesion, where enkephalin-containing neurons were more resistant than NADPH-diaphorase-containing cells. The size of the transition area around the lesion also differed depending upon excitotoxin and cell population. These results help to reconcile the controversy and suggest that with highly specified quantitative conditions quinolinic acid-induced injury of the striatum can resemble the histopathology of HD.
Roberts
R C
RC
Department of Psychiatry, University of Maryland School of Medicine, Baltimore 21228.
Ahn
A
A
Swartz
K J
KJ
Beal
M F
MF
DiFiglia
M
M
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004745:Enkephalins / Q000032:analysis / Q000378:metabolism; D007839:Functional Laterality; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008845:Microinjections; D009252:NADPH Dehydrogenase / Q000032:analysis / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D004745:Enkephalins; D009252:NADPH Dehydrogenase; D017378:Quinolinic Acid; D007608:Kainic Acid