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Dorrance, A. M.

Publications and source records attributed to Dorrance, A. M..

2 recordsLinked to original sources

Novel inductively-coupled ear-bars (ICEs) for fMRI signal enhancement in rat entorhinal cortex

Entorhinal cortex (EC) is a potential target of deep brain stimulation in Alzheimers disease (AD) and fMRI can enable whole-brain dynamic mapping noninvasively. However, it remains challenging to study EC-based fMRI connectivity in rodents due to image signal loss and the lower sensitivity of the surface coil ring or array coil for deep brain areas. To reduce the magnetic susceptibility artifacts driven signal loss issue, we introduced baby cream into the middle ear. To improve detection sensitivity, we implemented novel inductively-coupled ear-bars (ICEs) in the 7 T Bruker scanner, which resulted in an approximately 2-fold signal-to-noise ratio (SNR) increase in EC over the conventional surface array. The ICE can be conveniently utilized as an add-on device, with no modulation to the scanner interface. To demonstrate the applicability of ICEs for both task and resting-state (rs) fMRI, whole-brain echo-planar imaging (EPI) was performed in anesthetized rats modeling AD mixed dementia. Seed-based rs-fMRI connectivity maps emanating from the left entorhinal cortex demonstrated its connectivity to the hippocampus, piriform cortex, septal nuclei, and prefrontal cortex. Hence, this work demonstrates an optimized procedure for ICE by acquiring large scale networks emanating from a seed region that was not easily accessible by conventional MRI detectors, enabling better observation of EC-based brain fMRI connectivity studies with a higher signal-to-noise ratio in rodent models of dementia.

neuroscience↗

Interleukin-6 Drives Key Pathologic Outcomes in Experimental Acetaminophen-induced Liver Failure

Background and AimsIn severe cases of acetaminophen (APAP) overdose, acute liver injury rapidly progresses to acute liver failure (ALF), producing life-threatening complications including, hepatic encephalopathy (HE) and multi-organ failure (MOF). Systemic levels of interleukin-6 (IL-6) and IL-10 are highest in ALF patients with the most severe complications and the poorest prognosis. The mechanistic basis for dysregulation of these cytokines, and their association with outcome in ALF, remain poorly defined. MethodsTo investigate the impact of IL-6 and IL-10 in ALF, we used an experimental setting of failed liver repair after APAP overdose in which a high dose of APAP is administered (i.e., 500-600 mg/kg). Mice were treated with neutralizing antibodies to block IL-6 and IL-10. ResultsIn mice with APAP-induced ALF, high levels of IL-10 reduced monocyte recruitment and trafficking in the liver resulting in impaired clearance of dead cell debris. Kupffer cells in these mice, displayed features of myeloid-derived suppressor cells, including high level expression of IL-10 and PD-L1, which were increased in an IL-6-dependent manner. Similar to ALF patients with HE, cerebral blood flow was reduced in mice with APAP-induced ALF. Remarkably, although IL-6 is hepatoprotective in mice treated with low doses of APAP (i.e., 300 mg/kg), IL-6 neutralization in mice with APAP-induced ALF fully restored cerebral blood flow and reduced mortality. ConclusionCollectively, these studies demonstrate that exaggerated production of IL-6 in APAP-induced ALF triggers immune suppression (i.e., high levels of IL-10 and PD-L1), reduces cerebral blood flow (a feature of hepatic encephalopathy), disrupts liver repair (i.e., failed clearance of dead cells), and increases mortality.

pathology↗