BackgroundUremic toxicity may play a role in the elevated risk of developing cognitive impairment found among patients with CKD. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AhR), which is widely expressed in the central nervous system and which we previously identified as the receptor of indoxyl sulfate in endothelial cells.MethodsTo characterize involvement of uremic toxins in cerebral and neurobehavioral abnormalities in three rat models of CKD, we induced CKD in rats by an adenine-rich diet or by 5/6 nephrectomy; we also used AhR−/− knockout mice overloaded with indoxyl sulfate in drinking water. We assessed neurologic deficits by neurobehavioral tests and blood-brain barrier disruption by SPECT/CT imaging after injection of 99mTc-DTPA, an imaging marker of blood-brain barrier permeability.ResultsIn CKD rats, we found cognitive impairment in the novel object recognition test, the object location task, and social memory tests and an increase of blood-brain barrier permeability associated with renal dysfunction. We found a significant correlation between 99mTc-DTPA content in brain and both the discrimination index in the novel object recognition test and indoxyl sulfate concentrations in serum. When we added indoxyl sulfate to the drinking water of rats fed an adenine-rich diet, we found an increase in indoxyl sulfate concentrations in serum associated with a stronger impairment in cognition and a higher permeability of the blood-brain barrier. In addition, non-CKD AhR−/− knockout mice were protected against indoxyl sulfate–induced blood-brain barrier disruption and cognitive impairment.ConclusionsAhR activation by indoxyl sulfate, a uremic toxin, leads to blood-brain barrier disruption associated with cognitive impairment in animal models of CKD.

Background & Aims: The main restriction in the development of adult-adult Living Donor Liver Transplantation (LDLT) is the risk of morbidity and mortality for donors, which raises ethical questions. The objectives of this study are to review published studies dealing with morbidity and mortality in LDLT and to identify the proposed management and strategies for preventing donor mortality and morbidity in LDLT.Methods: The Medline database was searched from 2000 to 2017 using the MeSH terms “liver transplantation” and “morbidity” or “mortality” in combination with keywords “living donor liver transplantation”.Results: Among the 382 articles obtained, 43 articles were relevant for morbidity, 15 for mortality and 6 for both morbidity and mortality. Twenty-three papers reported donor deaths. The major cause of death was sepsis (30%). Morbidity ranged from 10% to 78.3% depending on the studies.Conclusions: The living donors’ morbidity and mortality is high, currently representing the main restriction in the development of LDLT. Some promising techniques, such as the donor portal vein flow modulation could lead to the further development of LDLT.

A soft, conformable, biocompatible strain sensor based on ultra-thin stretchable electronics is reported. The sensor comprises gold thin films patterned on a 50 μm thick polyurethane substrate to produce resistive-based strain sensors for monitoring bladder stretch. The sensor responds linearly as a function of strain from 0 to 50%, with an increasing sensitivity as a function of sensor length. The sensor displays good stability with very little hysteresis when it is subjected to cycling between 0 and a maximum strain of 50%, with the largest deviation between 0 and 50% strain of ∼19% after 100 cycles attributed to the sensor with the longest length (6 mm) because it physically stretches by a greater distance than sensors with a shorter length. “Breaking” tests on the sensor reveal that shorter sensors can withstand higher maximum strains than longer sensors. A biocompatible hydrogel adhesive is used to attach sensors in vitro to the outside wall of a pig’s bladder, and sensor performance is studied with respect to repeated bladder filling and emptying to investigate stretch changes. By monitoring bladder stretch and thus volume noninvasively, the sensor provides a route for developing new treatment options for various urological conditions.

Endothelial colony-forming cells (ECFCs) are promising candidates for cell therapy of ischemic diseases, as less than 10% of patients with an ischemic stroke are eligible for thrombolysis. We previously reported that erythropoietin priming of ECFCs increased their in vitro and in vivo angiogenic properties in mice with hindlimb ischemia. The present study used SPECT/CT to evaluate whether priming of ECFCs with erythropoietin could enhance their homing to the ischemic site after transient middle cerebral artery occlusion (MCAO) followed by reperfusion in rats and potentiate their protective or regenerative effect on blood-brain barrier (BBB) disruption, cerebral apoptosis, and cerebral blood flow (CBF). Methods: Rats underwent a 1-h MCAO followed by reperfusion and then 1 d after MCAO received an intravenous injection of either PBS (control, n 5 10), PBS-primed ECFCs (ECFC PBS , n 5 13), or erythropoietinprimed ECFCs (ECFC EPO , n 5 10). ECFC homing and the effect on BBB disruption, cerebral apoptosis, and CBF were evaluated by SPECT/CT up to 14 d after MCAO. The results were expressed as median 6 interquartile range for ipsilateral-to-contralateral ratio of the activity in middle cerebral artery-vascularized territories in each hemisphere. Histologic evaluation of neuronal survival and astrocytic proliferation was performed on day 14. Results: Erythropoietin priming increased homing of ECFCs to the ischemic hemisphere (ECFC PBS , 111.0% 6 16.0%; ECFC EPO , 146.5% 6 13.3%). BBB disruption was significantly reduced (control, 387% 6 153%; ECFC PBS , 151% 6 46% [P , 0.05]; ECFC EPO , 112% 6 9% [P , 0.001]) and correlated negatively with ECFC homing (Pearson r 5 20.6930, P 5 0.0002). Cerebral apoptosis was significantly reduced (control, 161% 6 10%; ECFC PBS , 141% 6 9% [P , 0.05]; ECFC EPO ,118% 6 5% [P , 0.001]) and correlated negatively with ECFC homing (r 5 20.7251, P , 0.0001). CBF was significantly restored with ECFCs and almost totally so with erythropoietin priming (control, 72% 6 2%; ECFC PBS , 90% 6 4% [P , 0.01]; ECFC EPO , 99% 6 4% [P , 0.001]) and correlated positively with ECFC homing (r 5 0.7348, P , 0.0001). Immunoblocking against the CD146 receptor on ECFCs highlighted its notable role in ECFC homing with erythropoietin priming (ECFC EPO , 147% 6 14%, n 5 4; ECFC EPO with antibody against CD146, 101% 6 12%, n 5 4 [P , 0.05]). Conclusion: Priming with erythropoietin before cell transplantation is an efficient strategy to amplify the migratory and engraftment capacities of ECFCs and their beneficial impact on BBB disruption, apoptosis, and CBF.