Causality of parenchymal and vascular changes in rats with experimental thiamine deficiency encephalopathy.
The causality of vascular and parenchymal damage to the central nervous system (CNS) was examined in rats with thiamine deficiency. Male Sprague-Dawley rats were divided into two groups; one was given a thiamine-deficient diet (TDD) and injected intraperitoneally with 10 micrograms/100 g bodyweight pyrithiamine (PT) in order to analyze morphometrically the topographical and sequential relationship between vascular and parenchymal changes and vasodilatation, and the other was given a TDD and 50 micrograms/100 g bodyweight PT in order to determine hemorrhagic sites using serial sections. Histological examination showed that spongiotic change occurred selectively in the inferior colliculus (100%) from day 19, and thereafter in the thalamus (95%), mammillary body (50%) and nuclei olivaris and vestibularis of the pons (25%), with or without hemorrhage. Simultaneously, glycogen accumulation was also observed in these regions at a frequency similar to that of hemorrhage. Ultrastructurally, however, hydropic swelling of astrocytic and neuronal processes without glycogen accumulation was observed as early as day 9 in the inferior colliculus, at which time an increase of glial fibrillary acidic protein-positive processes was also recognized. The superior colliculus was completely spared. From day 22 vasodilatation of the inferior colliculus occurred, concomitantly with bodyweight loss and neurological symptoms. Twenty-two examined hemorrhages, which occurred in the thalamus and inferior colliculus, were distributed along the arterioles or capillaries on the arterial side. In conclusion, the morphological CNS changes caused by thiamine deficiency with administration of low-dose PT in rats begin as hydropic swelling of neuronal and astrocytic processes, followed by hemorrhage and, thereafter, by vasodilation. The predilection for hemorrhage on the arterial side without parenchymal changes suggests that petechial hemorrhage is not simply secondary to parenchymal changes, but is due to hemodynamic change resulting from thiamine deficiency-induced vascular dysfunction.
Chen
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Q
Department of Neuropathology, Tokyo Medical and Dental University, Japan.
Okada
S
S
Okeda
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R
D000818:Animals; D000963:Antimetabolites; D001259:Ataxia / Q000139:chemically induced; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006003:Glycogen / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced; D007150:Immunohistochemistry; D007245:Inferior Colliculi / Q000098:blood supply / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008326:Mammillary Bodies / Q000098:blood supply / Q000473:pathology; D011745:Pyrithiamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced; D013788:Thalamus / Q000098:blood supply / Q000473:pathology; D013832:Thiamine Deficiency / Q000473:pathology*; D014664:Vasodilation / Q000187:drug effects; D014899:Wernicke Encephalopathy / Q000209:etiology / Q000473:pathology*
D000963:Antimetabolites; D005904:Glial Fibrillary Acidic Protein; D011745:Pyrithiamine; D006003:Glycogen