Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers.

Toxic protein aggregates can spread among neurons to promote human neurodegenerative disease pathology. We found that in C. elegans touch neurons intermediate filament proteins IFD-1 and IFD-2 associate with aggresome-like organelles and are required cell-autonomously for efficient production of neuronal exophers, giant vesicles that can carry aggregates away from the neuron of origin. The C. elegans aggresome-like organelles we identified are juxtanuclear, HttPolyQ aggregate-enriched, and dependent upon orthologs of mammalian aggresome adaptor proteins, dynein motors, and microtubule integrity for localized aggregate collection. These key hallmarks indicate that conserved mechanisms drive aggresome formation. Furthermore, we found that human neurofilament light chain (NFL) can substitute for C. elegans IFD-2 in promoting exopher extrusion. Taken together, our results suggest a conserved influence of intermediate filament association with aggresomes and neuronal extrusions that eject potentially toxic material. Our findings expand understanding of neuronal proteostasis and suggest implications for neurodegenerative disease progression.

Which Patients Receive Diagnostic Angiography? An EAST Multicenter Study Analysis of Internal Carotid Artery Blunt Cerebrovascular Injury.

BACKGROUND: Digital subtraction angiography (DSA) is the gold standard radiologic modality in blunt cerebrovascular injury (BCVI). However, computerized tomography angiography (CTA) is primarily used in modern practice with CTA's widespread availability and the decreased stroke rate with CTA use. The frequency and indications for DSA in BCVI is undefined. We hypothesized that DSA use in internal carotid artery (ICA) BCVI would be infrequent and dependent on radiologic features. METHODS: This was a post hoc analysis of an EAST multicenter, prospective, observational trial of 16 trauma centers for stroke factors in BCVI. ICA BCVI was divided into those undergoing DSA and not undergoing DSA (no-DSA). Only ICA BCVI was included. RESULTS: 332 ICA BCVI were included, 221 (66.6%) no-DSA and 111 (33.4%) DSA. Lower hospital trauma volume, non-urban environment, and non-academic status were associated with DSA use (all P ≤ .001). BCVI grade (P = .02) and presence of luminal stenosis (P = .005) were associated with DSA use while pseudoaneurysm presence was not. Median time to DSA was 1 hour. The most common indication for angiography was to determine the presence of injury in 71 (64%) ICA BCVI, followed by determining grade of injury in 16 (14.4%) and concerning imaging characteristics in 12 (10.8%). BCVI grade on initial imaging and on DSA were equivalent in 94 (84.7%) ICA BCVI. DISCUSSION: DSA is frequently used in ICA BCVI, primarily early in the hospital course for injury diagnosis and grade determination. DSA appears primarily driven by hospital type, BCVI grade, and luminal stenosis.