The ICV sign as a marker of increased cerebral blood transit time.

OBJECTIVE/BACKGROUND: We describe the internal cerebral vein (ICV) sign, which is a hypo-opacification of the ICV on computed tomogram angiography (CTA) as a new marker of increased cerebral blood transit-time in ipsilateral internal carotid artery occlusions (ICAO). METHODS: A retrospective analysis of 153 patients with acute unilateral M1 middle cerebral artery (MCA) occlusions ± ICAOs was performed. The degree of contrast opacification of the ICV on the ipsilesional side was compared to that of the unaffected side. RESULTS: Of 153 patients in our study, 135 had M1 MCA occlusions ± intra-cranial ICAO (M1±iICAO) and 18 had isolated extracranial ICAO (eICAO). In the patients with proximal M1±iICAO, 57/65 (87.1%) showed the ICV sign. Of the 8 patients without the ICV sign in this group, 6 had prominent lenticulostriate arteries arising from the non-occluded M1 segment, 1 had a recurrent artery of Huebner, and 1 had filling of distal ICA/M1 segment through prominent Circle of Willis collaterals. For the 70 patients with isolated distal M1±iICAO, 7/70 (10%) showed the ICV sign, with all 7 showing occluded lenticulostriate arteries. Of the patients with eICAO, 8/18 showed the ICV sign, all 8 with the ICV sign had poor Circle of Willis collaterals. CONCLUSIONS: The ICV sign correlates well with presence of proximal M1±iICAO in patients with either occluded lenticulostriate arteries or poor Circle of Willis collaterals. In patients with eICAO, the sign correlates with reduced Circle of Willis collaterals and may be a marker of increased ipsilateral cerebral blood transit time.

Phosphatidylethanolamine deficiency in Mammalian mitochondria impairs oxidative phosphorylation and alters mitochondrial morphology.

Mitochondrial dysfunction is implicated in neurodegenerative, cardiovascular, and metabolic disorders, but the role of phospholipids, particularly the nonbilayer-forming lipid phosphatidylethanolamine (PE), in mitochondrial function is poorly understood. Elimination of mitochondrial PE (mtPE) synthesis via phosphatidylserine decarboxylase in mice profoundly alters mitochondrial morphology and is embryonic lethal (Steenbergen, R., Nanowski, T. S., Beigneux, A., Kulinski, A., Young, S. G., and Vance, J. E. (2005) J. Biol. Chem. 280, 40032-40040). We now report that moderate <30% depletion of mtPE alters mitochondrial morphology and function and impairs cell growth. Acute reduction of mtPE by RNAi silencing of phosphatidylserine decarboxylase and chronic reduction of mtPE in PSB-2 cells that have only 5% of normal phosphatidylserine synthesis decreased respiratory capacity, ATP production, and activities of electron transport chain complexes (C) I and CIV but not CV. Blue native-PAGE analysis revealed defects in the organization of CI and CIV into supercomplexes in PE-deficient mitochondria, correlated with reduced amounts of CI and CIV proteins. Thus, mtPE deficiency impairs formation and/or membrane integration of respiratory supercomplexes. Despite normal or increased levels of mitochondrial fusion proteins in mtPE-deficient cells, and no reduction in mitochondrial membrane potential, mitochondria were extensively fragmented, and mitochondrial ultrastructure was grossly aberrant. In general, chronic reduction of mtPE caused more pronounced mitochondrial defects than did acute mtPE depletion. The functional and morphological changes in PSB-2 cells were largely reversed by normalization of mtPE content by supplementation with lyso-PE, a mtPE precursor. These studies demonstrate that even a modest reduction of mtPE in mammalian cells profoundly alters mitochondrial functions.