Limor Besser

Synaptically Released Zinc Triggers Metabotropic Signaling via a Zinc-Sensing Receptor in the Hippocampus

Zn2+ is coreleased with glutamate from mossy fiber terminals and can influence synaptic function. Here, we demonstrate that synaptically released Zn2+ activates a selective postsynaptic Zn2+-sensing receptor (ZnR) in the CA3 region of the hippocampus. ZnR activation induced intracellular release of Ca2+, as well as phosphorylation of extracellular-regulated kinase and Ca2+/calmodulin kinase II. Blockade of synaptic transmission by tetrodotoxin or CdCl inhibited the ZnR-mediated Ca2+ rises. The responses mediated by ZnR were largely attenuated by the extracellular Zn2+ chelator, CaEDTA, and in slices from mice lacking vesicular Zn2+, suggesting that synaptically released Zn2+ triggers the metabotropic activity. Knockdown of the expression of the orphan G-protein-coupled receptor 39 (GPR39) attenuated ZnR activity in a neuronal cell line. Importantly, we observed widespread GPR39 labeling in CA3 neurons, suggesting a role for this receptor in mediating ZnR signaling in the hippocampus. Our results describe a unique role for synaptic Zn2+ acting as the physiological ligand of a metabotropic receptor and provide a novel pathway by which synaptic Zn2+ can regulate neuronal function.

Synaptic release of zinc from brain slices : Factors governing release, imaging, and accurate calculation of concentration

Cerebrocortical neurons that store and release zinc synaptically are widely recognized as critical in maintenance of cortical excitability and in certain forms of brain injury and disease. Through the last 20 years, this synaptic release has been observed directly or indirectly and reported in more than a score of publications from over a dozen laboratories in eight countries. However, the concentration of zinc released synaptically has not been established with final certainty. In the present work we have considered six aspects of the methods for studying release that can affect the magnitude of zinc release, the imaging of the release, and the calculated concentration of released zinc. We present original data on four of the issues and review published data on two others. We show that common errors can cause up to a 3000-fold underestimation of the concentration of released zinc. The results should help bring consistency to the study of synaptic release of zinc.

Early onset preeclampsia and cerebral palsy: a double hit model?

BACKGROUND Cerebral palsy (CP) is a late sequel of pregnancy, and the role of preeclampsia is debatable. OBJECTIVE The aims of this study were to determine the association between preeclampsia and cerebral palsy and to determine the risk factors for the development of cerebral palsy in these patients. STUDY DESIGN A retrospective population-based cohort study was designed that included 229,192 singleton pregnancies. The study population was divided into 2 groups: (1) patients with preeclampsia (n = 9749) and (2) normotensive gestations (n = 219,443). Generalized Estimating Equation multiple logistic regression models were performed to study the associations among preeclampsia, small for gestational age, gestational age at delivery, and the risk factors for the development of cerebral palsy in neonates of women with preeclampsia. RESULTS The rate of cerebral palsy was double in patients with preeclampsia than in the normotensive group (0.2% vs 0.1%; P = .015); early onset preeclampsia and small for gestational age were independent risk factors for the subsequent development of cerebral palsy (odds ratio, 8.639 [95% confidence interval, 4.269-17.480]; odds ratio, 2.737 [95% confidence interval, 1.937-3.868], respectively). A second model was conducted to determine the risk factors for the development of cerebral palsy in women with preeclampsia. Birth asphyxia, complications of prematurity, and neonatal infectious morbidity, but not small for gestational age or gestational age at delivery, were independent risk factors for the development of cerebral palsy. CONCLUSION In a comparison with normal pregnant women, the rate of cerebral palsy is double among patients with preeclampsia, especially those with early-onset disease. Early-onset preeclampsia is an independent risk factor for cerebral palsy. Among women with preeclampsia, the presence of neonatal infectious morbidity, birth asphyxia, and complications of prematurity are independent risk factors for the development of cerebral palsy, which further supports the role of a multi-hit model in the pathogenesis of this syndrome.

Antenatal diagnosis and treatment of hypothyroid fetal goiter in an euthyroid mother: a case report and review of literature

Abstract Fetal goiter is an extremely rare complication of pregnancy. Its incidence is 1 in 40 000 deliveries. Antithyroid maternal therapy is responsible for 10–15% of fetal congenital hypothyroidism and can be considered as the most frequent underlying cause for this condition. The frequency of fetal goiter that is associated with fetal hypothyroidism and normal maternal thyroid function, as in our case, is even less frequent. Fetal goiter is associated with increased rate of perinatal complications and long-term morbidity, due to peripartum complications including labor dystocia due to its mass effect, as well as neonatal airway obstruction that may lead to hypoxic-ischemic brain injury and death. We present, in this study, a case report of late antenatal fetal goiter in an euthyroid woman and a literature review of the diagnosis and treatment of these cases.

The more you lose the more you miss: accuracy of postpartum blood loss visual estimation. A systematic review of the literature.

Abstract Midwives and nurses have a key role in monitoring postpartum period. They represent the first line professional figure in quantifying blood loss, initiating early diagnosis of obstetric hemorrhage, and mobilizing a team response, if needed. These actions are crucial in determining maternal outcome in postpartum hemorrhage (PPH). In our review we aimed to: (1) Provide a picture of PPH including its pathophysiology, epidemiology, and associated complications; (2) Discuss diagnosis of this dangerous postpartum event; and, (3) Especially evaluate the efficiency of the employment of visual blood loss estimation as a rapid way to suspect PPH and activate the patient assessment.

Comparative analysis of early adverse events of pelvic organ prolapse repair with or without transvaginal mesh using Clavien‐Dindo classification

To assess adverse events following surgical repair of pelvic organ prolapse (POP) with or without the use of transvaginal mesh.