Search Results for: 0

Inflammation increases neuronal sensitivity to general anesthetics

Avramescu S, Wang DS, Lecker I, To WTH, Penna A, Whissell PD, Mesbah-Oskui L, Horner RL and Orser BA. (2015) Anesthesiology (in press) Abstract Background: Critically ill patients with severe inflammation often exhibit heightened sensitivity to general anesthetics; however, the underlying mechanisms remain poorly understood. Inflammation increases the number of GABAA receptors expressed on the surface […]

α6-Containing GABAA Receptors Are the Principal Mediators of Inhibitory Synapse Strengthening by Insulin in Cerebellar Granule Cells

Accardi Mv, Brown PM, Miraucourt LS, Orser BA, Bowie D. (2015) J Neurosci 35(26): 9676-88 Abstract Activity-dependent strengthening of central synapses is a key factor driving neuronal circuit behavior in the vertebrate CNS. At fast inhibitory synapses, strengthening is thought to occur by increasing the number of GABAA receptors (GABARs) of the same subunit composition to […]

Thalamic δ-subunit containing GABAA receptors promote electrocortical signatures of deep non-REM sleep but do not mediate the effects of etomidate at the thalamus in vivo

Mesbah-Oskui L, Orser BA, Horner RL. (2014) J Neurosci. 34(37):12253-66 Abstract Extrasynaptic δ-subunits containing GABAA receptors (δGABAARs) are sensitive targets for several commonly used hypnotic agents and mediate tonic neuronal inhibition. δGABAARs are highly expressed within the thalamus and their activation promotes a switch from tonic to burst firing in vitro. Here we test two […]

Altered expression of δGABAA receptors in health and disease.

Whissell PD, Lecker I, Wang DS, Yu J, Orser BA. (2015) Neuropharmacology. 88:24-35. Abstract γ-Aminobutyric acid type A receptors that contain the δ subunit (δGABAA receptors) are expressed in multiple types of neurons throughout the central nervous system, where they generate a tonic conductance that shapes neuronal excitability and synaptic plasticity. These receptors regulate a […]

Anesthetic neurotoxicity–clinical implications of animal models

Rappaport BA, Suresh S, Hertz S, Evers AS, Orser BA. (2015) N Engl J Med. 372(9):796-7. Abstract Some anesthetics and sedatives have been shown to cause neurotoxic effects in laboratory animals. The FDA collaboration SmartTots recommends undertaking large-scale clinical studies and avoiding nonurgent surgical procedures requiring anesthesia in children younger than 3 years of age. […]

Sustained increase in α5GABA(A) receptor function impairs memory after anesthesia

Zurek AA, Yu J, Wang DS, Haffey SC, Bridgwater EM, Penna A, Lecker I, Lei G, Chang T, Salter EW, Orser BA. (2014) J Clin Invest. 124(12):5437-41. Abstract Many patients who undergo general anesthesia and surgery experience cognitive dysfunction, particularly memory deficits that can persist for days to months. The mechanisms underlying this postoperative cognitive […]

Hydrogen peroxide increases GABA(A) receptor-mediated tonic current in hippocampal neurons

Penna A, Wang DS, Yu J, Lecker I, Brown PM, Bowie D, Orser BA. (2014) J Neurosci. 34(32):10624-34. Abstract Hydrogen peroxide (H2O2), a key reactive oxygen species, is produced at low levels during normal cellular metabolism and at higher concentrations under pathological conditions such as ischemia-reperfusion injury. The mechanisms by which H2O2 contributes to physiological and pathological […]