title: Short- and long-term survival of large neurons in the excitotoxic lesioned rat caudate nucleus: a light and electron microscopic study.
abstract: Large striatal neurons are spared in caudate tissue from postmortem brain of patients with Huntington's disease (HD) and in the rat caudate lesioned with excitotoxins at short postlesion intervals. In order to determine the survival of large neurons and other effects of excitotoxicity at longer postlesion intervals the rat caudate nucleus was examined 2, 7, and 30 weeks after intrastriatal injections of the excitotoxin, quinolinic acid. The caudate nucleus diminished in size progressively up to 30 weeks postlesion due to 1) shrinkage and compacting of the lesion zone and 2) reduction in area of intact caudate, apparently due to gradual loss of the remaining caudate neurons. In Nissl-stained sections of the lesion zone where total neuronal density was less than 5% of contralateral control, large neurons were present at all postlesion intervals, forming 38-58% of the remaining neurons. Unexpectedly, a fivefold reduction in the number of large neurons was observed between 2 and 30 weeks postlesion. Also, at 7 and 30 weeks postlesion most of the large neurons were confined to the peripheral region of the lesion. At all postlesion intervals, large neurons retained ultrastructural integrity and some synaptic inputs despite the severe disruption of the surrounding neuropil. Surrounding the lesion zone was a transition zone which exhibited a decrease in total neuronal density to 53-74% of control. In this region the density of large neurons was not diminished, and the proportion of large neurons was elevated in comparison to that of controls at all postlesion intervals. Findings suggest that following excitotoxic lesion of the caudate nucleus there are marked differences between short- and long-term postlesion intervals in the survival and distribution of large neurons. We speculate that an imbalance in the synaptic connections with other caudate neurons leads to the persistent loss of large neurons in the lesion zone at long postlesion intervals. A transition zone surrounding the lesion, where cell loss is less severe than in the lesion zone, exhibits features more characteristic of the neuropathology of HD.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston.
authors.forename: R C
authors.initials: RC
authors.lastname: Roberts
authors.forename: M
authors.initials: M
authors.lastname: DiFiglia
mesh_terms: D000818:Animals; D001284:Atrophy; D002421:Caudate Nucleus / Q000166:cytology* / Q000187:drug effects; D002470:Cell Survival; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000145:classification / Q000648:ultrastructure; D011725:Pyridines / Q000633:toxicity*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D011725:Pyridines; D011805:Quinolinic Acids; D017378:Quinolinic Acid