Management of Malignant Middle Cerebral Artery Infarction

Malignant middle cerebral artery (MCA) infarcts occur in a small subset of patients with ischaemic strokes and lead to high levels of disability and mortality. Over the last 10 years, surgical interventions, in the form of decompressive craniectomies, have become more popular. There is insufficient evidence to support current medical treatments including mannitol, glycerol, steroids, hypertonic saline, and therapeutic hypothermia. Several randomised controlled trials of early decompressive craniectomies in younger patients have shown a significant improvement in functional outcomes and mortality. Questions still need answering regarding the timing of this surgery, long-term survival benefits, and age thresholds. In this review article we will discuss the evidence and uncertainties surrounding the management of malignant MCA infarcts

Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45

Insulin stimulates glucose transport in fat and muscle cells by regulating delivery of the facilitative glucose transporter, glucose transporter isoform 4 (GLUT4), to the plasma membrane. In the absence of insulin, GLUT4 is sequestered away from the general recycling endosomal pathway into specialized vesicles, referred to as GLUT4-storage vesicles. Understanding the sorting of GLUT4 into this store is a major challenge. Here we examine the role of the Sec1/Munc18 protein mVps45 in GLUT4 trafficking. We show that mVps45 is up-regulated upon differentiation of 3T3-L1 fibroblasts into adipocytes and is expressed at stoichiometric levels with its cognate target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor, syntaxin 16. Depletion of mVps45 in 3T3-L1 adipocytes results in decreased GLUT4 levels and impaired insulin-stimulated glucose transport. Using sub-cellular fractionation and an in vitro assay for GLUT4-storage vesicle formation, we show that mVps45 is required to correctly traffic GLUT4 into this compartment. Collectively our data reveal a crucial role for mVps45 in the delivery of GLUT4 into its specialized, insulin-regulated compartment