Early Edematous Lesion of Pyrithiamine Induced Acute Thiamine Deficient Encephalopathy in the Mouse

Abstract

Pyrithiamine induced acute thiamine deficient encephalopathy in the mouse is one of the possible animal models of human Wernicke-Korsakoff syndrome. In this experiment, the adult male Swiss Mice, treated with a daily subcutaneous injection of pyrithiamine in conjunction with a thiamine deficient diet, abruptly developed unique encephalopathic signs on day 10. In the animals sacrificed immediately after the onset of the disease, the gross examination of the brains revealed a small number of minute hemorrhagic lesions in the thalamus, mammilary bodies and pontine tegmentum, including the medial and lateral vestibular nuclei. When spared the hemorrhage, these regions appear intact grossly and in paraffin sections, but were found to be significantly altered in Epon sections. In semithin Epon sections of the pontine tegmentum, there was edematous swelling of all the astrocytes and oligodendrocytes and occasional myelin sheaths. By electron microscopy, the edema of astrocytes involved both nucleus and cytoplasm extensively. The oligodendroglial edema was severe in the peripheral cytoplasm, particularly in the inner loops of the myelin sheaths and only moderately in the nuclei, perinuclear cytoplasm and outer loops. Disintegration of the myelin lamellae occurred when edema of the inner loops had advanced. The axis cylinders surrounded by the edematous loops were essentially intact. In contrast to such glial cell damage, the nerve cells and blood vessels were not altered. These findings suggest that (1) astroglia and oligodendroglia are the cells most sensitive to thiamine deficiency and (2) the resultant glial cell injury is the initial change of thiamine deficient encephalopathy in man and in experimental animals.

Thiamine Deficiency Induces Massive Cell Death in the Olfactory Bulbs of Mice

“…It is established that the thalamic nuclei, mammillary bodies, inferior colliculi, and vestibular nuclei are affected in PTD rodents (7,29). Using ssDNA immunohistochemistry in the present study, however, we could not detect PTD-induced cell death in the mammillary bodies, although dying cells were detected by the TUNEL method.…”

Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy

“…Enlargement of the ventricles has previously been reported in thiamine deficiency (Dror et al, 2010), but this MR metric is a non-specific index of brain pathology (e.g., Zahr et al, 2013). The edematous nature of inferior collicular pathology (Watanabe and Kanabe, 1978) may explain why it is detected early in the course of in thiamine deficiency by in vivo MRI, which is sensitive to brain pathology caused by tissue edema (Jung et al, 2012). As with ventricular enlargement, however, hyperintensities noted on T2-weighted scans are nonspecific and reflect several different tissue processes including, but not limited to, edema, cellular infiltration, gliosis, demyelination, and severe necrosis (Pirko and Johnson, 2008).…”

Protective effects of the glutamate antagonist MK-801 on pyrithiamine- induced lesions and amino acid changes in rat brain

“…Several obervations suggest a sudden rise in extracellular fluid levels of glutamate and aspartate within vulnerable regions could occur during acute thiamine deficiency. Edematous swelling of glia is the earliest morphologic change to occur in thiamine deficiency encephalopathy (Collins, 1967;Robertson et al, 1968;Collins and Converse, 1970;Watanabe and Kanabe, 1978;Watanabe et al, 198 1). Glia cells possess a very high uptake rate for aspartate and glutamate (Hertz, 1979) and are considered to play an important role in the rapid inactivation and overall regulation of extracellular levels of excitatory amino acids (Henn, 1976;Walker, 1983;Reynolds and Herschkowitz, 1986).…”