Leucine-Rich Alpha-2-Glycoprotein 1 is a Systemic Biomarker of Early Brain Injury and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

BACKGROUND: After subarachnoid hemorrhage (SAH), early brain injury (EBI) and delayed cerebral ischemia (DCI) lead to poor outcomes. Discovery of biomarkers indicative of disease severity and predictive of DCI is important. We tested whether leucine-rich alpha-2-glycoprotein 1 (LRG1) is a marker of severity, DCI, and functional outcomes after SAH. METHODS: We performed untargeted proteomics using mass spectrometry in plasma samples collected at < 48 h of SAH in two independent discovery cohorts (n = 27 and n = 45) and identified LRG1 as a biomarker for DCI. To validate our findings, we used enzyme-linked immunosorbent assay and confirmed this finding in an internal validation cohort of plasma from 72 study participants with SAH (22 DCI and 50 non-DCI). Further, we investigated the relationship between LRG1 and markers of EBI, DCI, and poor functional outcomes (quantified by the modified Rankin Scale). We also measured cerebrospinal fluid (CSF) levels of LRG1 and investigated its relationship to EBI, DCI, and clinical outcomes. RESULTS: Untargeted proteomics revealed higher plasma LRG1 levels across EBI severity and DCI in both discovery cohorts. In the validation cohort, the levels of LRG1 were higher in the DCI group compared with the non-DCI group (mean (SD): 95 [44] vs. 72 [38] pg/ml, p < 0.05, Student's t-test) and in study participants who proceeded to have poor functional outcomes (84 [39.3] vs. 72 [43.2] pg/ml, p < 0.05). Elevated plasma LRG1 levels were also associated with markers of EBI. However, CSF levels of LRG1 were not associated with EBI severity or the occurrence of DCI. CONCLUSIONS: Plasma LRG1 is a biomarker for EBI, DCI, and functional outcomes after SAH. Further studies to elucidate the role of LRG1 in the pathophysiology of SAH are needed.

Calsenilin is degraded by the ubiquitin-proteasome pathway.

Calsenilin, a neuronal calcium binding protein that has been shown to have multiple functions in the cell, interacts with presenilin 1 (PS1) and presenilin 2 (PS2), represses gene transcription and binds to A-type voltage-gated potassium channels. In addition, increased levels of calsenilin are observed in the brains of Alzheimer's disease and epilepsy patients. The present study was designed to investigate the molecular mechanism of calsenilin degradation pathways in cultured cells. Here, we demonstrate that inhibition of the ubiquitin-proteasomal pathway (UPP) but not lysosomal pathway markedly increased the expression levels of calsenilin. Immunofluorescence analysis revealed that following proteasomal inhibition calsenilin accumulated in the endoplasmic reticulum (ER) and Golgi, while lysosomal inhibition had no effect on calsenilin localization. In addition, we found the change of subcellular localization of PS1 from diffuse pattern to punctuate staining pattern in the ER and perinuclear region in the presence of calsenilin. These findings suggest that calsenilin degradation is primarily mediated by the UPP and that impairment in the UPP may contribute to the involvement of calsenilin in disease-associated neurodegeneration.

A comparison of infraclavicular and supraclavicular approaches to the brachial plexus using neurostimulation.

BACKGROUND: A prospective, double blind study was performed to compare the clinical effect of vertical infraclavicular and supraclavicular brachial plexus block using a nerve stimulator for upper limb surgery. METHODS: One hundred patients receiving upper limb surgery under infraclavicular or supraclavicular brachial plexus block were enrolled in this study. The infraclavicular brachial plexus block was performed using the vertical technique with 30 ml of 0.5% ropivacaine. The supraclavicular brachial plexus block was performed using the plumb bob technique with 30 ml of 0.5% ropivacaine. The block performance-related pain was evaluated. This study observed which nerve type was stimulated, and scored the sensory and motor block. The quality of the block was assessed intra-operatively. The duration of the sensory and motor block as well as the complications were assessed. The patient's satisfaction with the anesthetic technique was assessed after surgery. RESULTS: There were no significant differences in the block performance-related pain, frequency of the stimulated nerve type, evolution of sensory and motor block quality, or the success of the block. There were no significant differences in the duration of the sensory and motor block. There was a significant difference in the incidence of Horner's syndrome. Two patients had a pneumothorax in the supraclavicular approach. There were no significant differences in the patient's satisfaction. CONCLUSIONS: Both infraclavicular and supraclavicular brachial plexus block had similar effects. The infraclavicular approach may be preferred to the supraclavicular approach when considering the complications.