A simple novel approach for detecting blood-brain barrier permeability using GPCR internalization.

AIMS: Impairment of blood-brain barrier (BBB) is involved in numerous neurological diseases from developmental to aging stages. Reliable imaging of increased BBB permeability is therefore crucial for basic research and preclinical studies. Today, the analysis of extravasation of exogenous dyes is the principal method to study BBB leakage. However, these procedures are challenging to apply in pups and embryos and may appear difficult to interpret. Here we introduce a novel approach based on agonist-induced internalization of a neuronal G protein-coupled receptor widely distributed in the mammalian brain, the somatostatin receptor type 2 (SST2). METHODS: The clinically approved SST2 agonist octreotide (1 kDa), when injected intraperitoneally does not cross an intact BBB. At sites of BBB permeability, however, OCT extravasates and induces SST2 internalization from the neuronal membrane into perinuclear compartments. This allows an unambiguous localization of increased BBB permeability by classical immunohistochemical procedures using specific antibodies against the receptor. RESULTS: We first validated our approach in sensory circumventricular organs which display permissive vascular permeability. Through SST2 internalization, we next monitored BBB opening induced by magnetic resonance imaging-guided focused ultrasound in murine cerebral cortex. Finally, we proved that after intraperitoneal agonist injection in pregnant mice, SST2 receptor internalization permits analysis of BBB integrity in embryos during brain development. CONCLUSIONS: This approach provides an alternative and simple manner to assess BBB dysfunction and development in different physiological and pathological conditions.

Safe short circuit in cataract surgery: Incidence and risk factors for intraoperative medical action.

Cataract surgery has become the most frequent surgical procedure performed every year in Western countries. Perioperative patient circuit has to be adapted to the important medical needs and progress. Hence, a secure short circuit (SSC) for surgeries of the anterior segment of the eye under topical anaesthesia was created. Patients included in the circuit are selected first by surgeons and answer a medical questionnaire, they do not have any preoperative evaluation by anaesthesiologist, are monitored during surgery by the surgical team and in case of problem an intraoperative medical action (IMA) can be performed. We conducted a retrospective observational incidence study of the occurrence of the IMA, followed by a case control study. The primary outcome was to identify risk factors of IMA among the patients' medical history. Out of 2744 screened patients, 1592 patients were included during the period of November 2015 to November 2017. The rate of IMA was 5%, 81% of them presenting with intraoperative high blood pressure (HBP). In the case control study part, stepwise regression analysis revealed that a history of HBP and insulin-dependent diabetes (IDD) was significantly correlated with IMA (respectively, adjusted odds ratio 1.7, P=0.005 and 2.6, P=0.002). The low incidence of IMA showed that the SSC is a safe tool thanks to a selection and an optimised and secure pathway. A history of HBP and IDD was significantly associated with the occurrence of IMA. Therefore, an optimisation of the perioperative period would be beneficial in these cases.