Anosognosia and the intracarotid amobarbital procedure (Wada test)

Abstract

Microsomal triglyceride transfer protein (MTP)is an intraluminal protein in the endoplasmic reticulum (ER) that is essential for the assembly of apolipoprotein B (apoB)-containing lipoproteins. In this study, we examine how the livers of mice respond to two distinct methods of blocking MTP function: Cre -mediated disruption of the gene for MTP and chemical inhibition of MTP activity. Blocking MTP significantly reduced plasma levels of triglycerides, cholesterol, and apoB-containing lipoproteins in both wild-type C57BL/6 and LDL receptor-deficient mice. While treating LDL receptor-deficient mice with an MTP inhibitor for 7 days lowered plasma lipids to control levels, liver triglyceride levels were increased by only 4-fold. Plasma levels of apoB-100 and apoB-48 fell by Ͼ 90% and 65%, respectively, but neither apoB isoform accumulated in hepatic microsomes. Surprisingly, loss of MTP expression was associated with a nearly complete absence of apoB-100 in hepatic microsomes. Levels of microsomal luminal chaperone proteins [e.g., protein disulfide isomerase, glucoseregulated protein 78 (GRP78), and GRP94] and cytosolic heat shock proteins (HSPs) (e.g., HSP60, HSC, HSP70, and HSP90) were unaffected by MTP inhibition. These findings show that the liver responds rapidly to inhibition of MTP by degrading apoB and preventing its accumulation in the ER.The rapid degradation of secretion-incompetent apoB in the ER may block the induction of proteins associated with unfolded protein and heat shock responses. -Liao, W., T. Y. Hui, S. G. Young, and R. Davis. Blocking microsomal triglyceride transfer protein interferes with apoB secretion without causing retention or stress in the ER. J. Lipid Res. 2003. 44: 978-985.Supplementary key words apolipoprotein B • endoplasmic reticulum • hyperlipidemia • liver • inflammation • unfolded protein response Abbreviations: ALLN, acetylated leucine, leucine, norleucal; ER, endoplasmic reticulum; GRP, glucose-regulated protein; HSP, heat shock protein; MTP, microsomal triglyceride transfer protein; PDI, protein disulfide isomerase.

Possible mechanisms of anosognosia of hemiplegia

“…A subsequent study failed to replicate our findings (Dywan, McGlone, & Fox, 1995); however, other studies were able to replicate these findings (Carpenter et al, 1995;Durkin, Meador, Nichols, Lee, & Loring, 1994). The reason why Dywan et al's study did not replicate our study is not known, but occasionally we do observe patients who with left hemisphere anesthesia were not aware of their weakness and other patients who are aware of their weakness after right hemisphere anesthesia.…”

Anosognosia for motor impairment following left brain damage.

“…Despite a trend toward a higher frequency of anosognosia following suppression of right hemisphere activity, presence of unawareness following suppression of left hemisphere activity ranged from 49% (Breier et al, 1995) to 86% (Durkin, Meador, Nichols, Lee, & Loring, 1994). …”

“…Studies using the Wada test that were carried out with a large group of volunteers (e.g., Dywan, McGlone, & Fox, 1995) showed a different pattern of results (see Table 1). Despite a trend toward a higher frequency of anosognosia following suppression of right hemisphere activity, presence of unawareness following suppression of left hemisphere activity ranged from 49% (Breier et al, 1995) to 86% (Durkin, Meador, Nichols, Lee, & Loring, 1994).…”

Assessing anosognosia: a critical review

“…This is a clear limitation in studies attempting to assess anosognosia in aphasic patients, and has led to high exclusion rates of left brain damaged patients, and possible underestimation of anosognosia for right hemiplegia (e.g., Cutting, 1978;Morin et al, 2007;Cocchini et al, 2009). Studies capi talising on the intra-carotid sodium amobarbital procedure (Wada test) did show a higher frequency of anosognosia for left hemiplegia after anesthesia of the right hemisphere; however, they also indicated that when the left hemisphere was inactivated, the frequency of anosognosia for right hemiplegia varied greatly, ranging from zero (Gilmore et al, 1992) to 86% (Durkin et al, 1994). It follows that the apparent strong hemispheric asymmetry that has guided research and theoretical interpretations may suffer from a methodological bias, and the left hemisphere may play some role in awareness, even if probably less crucial than or different from that of the right hemisphere.…”