Abstract
Neuroinflammation is an important pathogenesis of hepatic encephalopathy (HE). The upregulation of translocator protein (TSPO) during neuroinflammation provides an imaging molecular target to evaluate the severity of neuroinflammation in chronic HE rats. [18F]DPA-714 and [18F]PBR146 targeting TSPO are often used for neuroinflammation imaging. This study performed bile duct ligation (BDL) in rats to simulate chronic HE model, tested the behavioral experiments, and conducted [18F]PBR146 and [18F]DPA-714 micro-PET/CT scans followed analyzing the average %ID/g values of the whole brain, brain regions and main organs of subjects. After sacrifice the rats, the blood plasma samples were taken for blood biochemical indexes and plasma inflammatory factor levels examination, the liver and brain specimens were obtained for pathological analysis. The BDL rats showed chronic liver failure with defects in cognition, motor coordination ability and mental state. [18F]PBR146 and [18F]DPA-714 micro-PET/CT imaging results were similar in whole brain of BDL group and Sham group. Besides, some regional brain areas in BDL rats were found abnormal uptakes mainly located in basal ganglia area, auditory cortex, motor cortex, cingulate gyrus, somatosensory cortex, hippocampus, thalamus, midbrain, and medulla oblongata, and these regions also correlated with behavioral alterations. In conclusion, both [18F]PBR146 and [18F]DPA-714 had the similar imaging effects in hepatic encephalopathy models could quantitatively evaluate neuroinflammation load and distribution. The difference brain regions with higher uptake values of radiotracers in BDL rats were correlated with behavioral alterations.
Highlights
Hepatic encephalopathy (HE) is a serious complication characterized by advanced liver failure and a spectrum of neuropsychiatric impairments ranging from minimal HE to delirium or coma, which are correlated with a poor prognosis (Bajaj, 2018; Kerbert and Jalan, 2020)
Higher translocator protein (TSPO) expression in activated microglia during neuroinflammation provides a novel target for radiotracers in positron emission tomography (PET) imaging in order to identify neuroinflammation in various central nervous system diseases (Alam et al, 2017)
In the present study, [18F]PBR146 and [18F]DPA-714 uptake values were measured in the brains and organs of rats modeling chronic HE compared to control model rats
Summary
Hepatic encephalopathy (HE) is a serious complication characterized by advanced liver failure and a spectrum of neuropsychiatric impairments ranging from minimal HE to delirium or coma, which are correlated with a poor prognosis (Bajaj, 2018; Kerbert and Jalan, 2020). Systemic inflammation and hyperammonemia attributed to acute and chronic liver failure induce neuroinflammation and Neuroinflammation Imaging in Hepatic Encephalopathy brain dysfunction (Butterworth, 2013). Radiolabeled ligands targeting TSPO for positron emission tomography (PET) help visualize the distribution of TSPO in vivo in order to detect activated microglia in the brain. They have been considered a novel biomarker for neuroinflammation, and more than 40 TSPO compounds labeled with [11C] or [18F] have been identified over the past two decades (Alam et al, 2017)
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