Protective effect of lesion to the glutamatergic cortico-striatal projections on the hypoglycemic nerve cell injury in rat striatum.
In rat striatum severe hypoglycemia causes an irreversible nerve cell injury, which does not become manifest until during the post-insult recovery period. This injury can be ameliorated by lesions of the glutamatergic cortico-striatal pathway, which suggests that an "excitotoxic" effect mediated by the glutamatergic input is the likely cause of the post-hypoglycemic nerve cell destruction. In this paper we further characterize the protective effect of abolishing the glutamatergic innervation to striatum at the ultrastructural level. Two weeks after a unilateral cortical ablation rats were subjected to 30 min of severe hypoglycemia with isoelectric EEG and killed either immediately after the insult or following 60 min of recovery induced by restoring the blood glucose levels. Immediately after the hypoglycemic insult the structure of striatum was similar on both sides (except for the changes attributable to the ablation); i.e., the neurons and their dendrites had pale cytoplasm with condensed mitochondria, sparse RER and pinpoint ribosomes. After 60 min restitution numerous striatal neurons on the non-protected, non-ablated side had turned variably dark and condensed, whereas underneath the ablation they remained similar as immediately after hypoglycemia. This sequence indicates that the most likely cause of nerve cell destruction on the non-protected side is the "excitotoxic" effect mediated by the glutamatergic innervation, which is superimposed on the action of the hypoglycemic insult per se. Furthermore, the primary condensation of neurons and their dendrites indicate existence of another type of acute "excitotoxic" nerve cell injury which differs from the previously described injury characterized by neuronal swelling.
Department of Pathology I, University of Gothenburg, Sweden.
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Linden
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Kalimo
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Wieloch
D000818:Animals; D002421:Caudate Nucleus / Q000473:pathology / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000473:pathology*; D003342:Corpus Striatum / Q000473:pathology* / Q000648:ultrastructure; D007003:Hypoglycemia / Q000473:pathology*; D008854:Microscopy, Electron; D009434:Neural Pathways / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D011699:Putamen / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains