Intraoperative Electroencephalography Alpha-Band Power Is a Better Proxy for Preoperative Low MoCA Under Propofol Compared With Sevoflurane.

BACKGROUND: Preoperative abnormal cognitive status is a risk factor for postoperative complications yet remains underdiagnosed. During propofol general anesthesia, intraoperative electroencephalography (EEG) variables, such as alpha band power (α-BP), correlate with cognitive status. This relationship under sevoflurane is unclear. We investigated whether EEG biomarkers of poor cognitive status found under propofol could be extended to sevoflurane. METHODS: In this monocentric prospective observational study, 106 patients with intraoperative EEG monitoring were included (propofol/sevoflurane = 55/51). We administered the Montreal Cognitive Assessment (MoCA) scale to identify abnormal cognition (low MoCA) 1 day before intervention. EEG variables included delta to beta frequency band powers. Results were adjusted to age and drug dosage. We assessed depth of anesthesia (DoA) using the spectral edge frequency (SEF 95 ) and maintained it within (8-13) Hz. RESULTS: The difference in α-BP between low and normal MoCA patients was significantly larger among propofol patients (propofol: 4.3 ± 4.8 dB versus sevoflurane: 1.5 ± 3.4 dB, P = .022). SEF 95 and age were not statistically different between sevoflurane and propofol groups. After adjusting to age and dose, low α-BP was significantly associated with low MoCA under propofol (odds ratio [OR] [confidence interval {CI}] = 0.39 [0.16-0.94], P = .034), but not under sevoflurane, where theta-band power was significantly associated with low MoCA (OR [CI] = 0.31 [0.13-0.73], P = .007). CONCLUSIONS: We suggest that intraoperative EEG biomarkers of abnormal cognition differ between propofol and sevoflurane under general anesthesia.

Determinants of Post-Operative Cognitive Decline in Elderly People.

BACKGROUND: Surgery and anesthesia can result in temporary or permanent deterioration of the cognitive functions, for which causes remain unclear. OBJECTIVES: In this pilot study, we analyzed the determinants of cognitive decline following a non-emergency elective prosthesis implantation surgery for hip or knee. DESIGN: Prospective single-center study investigating psychomotor response time and changes in MoCA scores between the day before (D-1) and 2 days after (D+2) following surgery at the Lariboisière Hospital (Paris, France). PARTICIPANTS: 60 patients (71.9±7.1-year-old, 72% women) were included. MEASUREMENTS: Collected data consisted in sociodemographic data, treatments, comorbidities and the type of anesthesia (local, general or both). Furthermore, we evaluated pain and well-being before as well as after the surgery using point scales. RESULTS: Post-operative (D+2) MoCA scores were significantly lower than pre-operative ones (D-1) with a median difference of 2 pts [IQR]=4pts, (p<0.001), we found no significant difference between locoregional and general anesthesia. Pre-operative benzodiazepine or anticholinergic treatments were also associated to a drop in MoCA scores (p=0.006). Finally, the use of ketamine during anesthesia (p=0.043) and the well-being (p=0.006) evaluated before intervention, were both linked to a reduced cognitive impact. CONCLUSION: In this pilot study, we observed a post-operative short-term cognitive decline following a lower limb surgery. We also identified pre and perioperative independent factors linked to cognitive decline following surgery. In a next stage, a larger cohort should be used to confirm the impact of these factors on cognitive decline.

Steady-state voltage distribution in three-dimensional cusp-shaped funnels modeled by PNP.

We study here the bulk electro-diffusion properties of micro- and nanodomains containing a cusp-shaped structure in three-dimensions when the cation concentration dominates over the anions. To determine the consequences on the voltage distribution, we use the steady-state Poisson-Nernst-Planck equation with an integral constraint for the number of charges. A non-homogeneous Neumann boundary condition is imposed on the boundary. We construct an asymptotic approximation for certain surface charge distribution that agree with numerical simulations. Finally, we analyze the consequences of several piecewise constant non-homogeneous surface charge densities, motivated by designing new nanopipettes. To conclude, when electro-neutrality is broken at the scale of hundreds of nanometers, the geometry of cusp-shaped domains influences the voltage profile, specifically inside the cusp structure. The main results are summarized in the form of new three-dimensional electrostatic laws for non-electroneutral electrolytes. These formula provide a refined characterization of voltage distribution at steady-state in neuronal microdomains such as dendritic spines, but can also be used to design nanometric patch-pipettes.

Electrical transient laws in neuronal microdomains based on electro-diffusion.

The current-voltage (I-V) conversion characterizes the physiology of cellular microdomains and reflects cellular communication, excitability, and electrical transduction. Yet deriving such I-V laws remains a major challenge in most cellular microdomains due to their small sizes and the difficulty in assessing voltage with high nanometer precision. We present here novel analytical relations derived for different numbers of ionic species inside neuronal micro/nano-domains, such as dendritic spines. When a steady-state current is injected, we find a large deviation from the classical Ohm's law, showing that the spine neck resistance is insufficient to characterize electrical properties. For a constricted spine neck, modeled by a hyperboloid, we obtain a new I-V law that illustrates the consequences of narrow passages on electrical conduction. Finally, during a fast current transient, the local voltage is modulated by the distance between activated voltage-gated channels. To conclude, electro-diffusion laws can now be used to interpret voltage distribution in neuronal microdomains.

Electrostatics of non-neutral biological microdomains.

Voltage and charge distributions in cellular microdomains regulate communications, excitability, and signal transduction. We report here new electrical laws in a biological cell, which follow from a nonlinear electro-diffusion model. These newly discovered laws derive from the geometrical cell-membrane properties, such as membrane curvature, volume, and surface area. The electro-diffusion laws can now be used to predict and interpret voltage distribution in cellular microdomains such as synapses, dendritic spine, cilia and more.

Crystal structure of the D85S mutant of bacteriorhodopsin: model of an O-like photocycle intermediate.

Crystal structures are reported for the D85S and D85S/F219L mutants of the light-driven proton/hydroxyl-pump bacteriorhodopsin. These mutants crystallize in the orthorhombic C222(1) spacegroup, and provide the first demonstration that monoolein-based cubic lipid phase crystallization can support the growth of well-diffracting crystals in non-hexagonal spacegroups. Both structures exhibit similar and substantial differences relative to wild-type bacteriorhodopsin, suggesting that they represent inherent features resulting from neutralization of the Schiff base counterion Asp85. We argue that these structures provide a model for the last photocycle intermediate (O) of bacteriorhodopsin, in which Asp85 is protonated, the proton release group is deprotonated, and the retinal has reisomerized to all-trans. Unlike for the M and N photointermediates, where structural changes occur mainly on the cytoplasmic side, here the large-scale changes are confined to the extracellular side. As in the M intermediate, the side-chain of Arg82 is in a downward configuration, and in addition, a pi-cloud hydrogen bond forms between Trp189 NE1 and Trp138. On the cytoplasmic side, there is increased hydration near the surface, suggesting how Asp96 might communicate with the bulk during the rise of the O intermediate.

Coupling photoisomerization of retinal to directional transport in bacteriorhodopsin.

In order to understand how isomerization of the retinal drives unidirectional transmembrane ion transport in bacteriorhodopsin, we determined the atomic structures of the BR state and M photointermediate of the E204Q mutant, to 1.7 and 1.8 A resolution, respectively. Comparison of this M, in which proton release to the extracellular surface is blocked, with the previously determined M in the D96N mutant indicates that the changes in the extracellular region are initiated by changes in the electrostatic interactions of the retinal Schiff base with Asp85 and Asp212, but those on the cytoplasmic side originate from steric conflict of the 13-methyl retinal group with Trp182 and distortion of the pi-bulge of helix G. The structural changes suggest that protonation of Asp85 initiates a cascade of atomic displacements in the extracellular region that cause release of a proton to the surface. The progressive relaxation of the strained 13-cis retinal chain with deprotonated Schiff base, in turn, initiates atomic displacements in the cytoplasmic region that cause the intercalation of a hydrogen-bonded water molecule between Thr46 and Asp96. This accounts for the lowering of the pK(a) of Asp96, which then reprotonates the Schiff base via a newly formed chain of water molecules that is extending toward the Schiff base.

Annexin XII E105K crystal structure: identification of a pH-dependent switch for mutant hexamerization.

Annexins are a family of calcium- and phospholipid-binding proteins involved with numerous cellular processes including membrane fusion, ion channel activity, and heterocomplex formation with other proteins. The annexin XII (ANXB12) crystal structure presented evidence that calcium mediates the formation of a hexamer through a novel intermolecular calcium-binding site [Luecke et al. (1995) Nature 378, 512-515]. In an attempt to disrupt hexamerization, we mutated a conserved key ligand in the intermolecular calcium-binding site, Glu105, to lysine. Despite its occurrence in a new spacegroup, the 1.93 A resolution structure reveals a hexamer with the Lys105 epsilon-amino group nearly superimposable with the original intermolecular calcium position. Our analysis shows that the mutation is directly involved in stabilizing the hexamer. The local residues are reoriented to retain affinity between the two trimers via a pH-dependent switch residue, Glu76, which is now protonated, allowing it to form tandem hydrogen bonds with the backbone carbonyl and nitrogen atoms of Thr103 located across the trimer interface. The loss of the intermolecular calcium-binding site is recuperated by extensive hydrogen bonding favoring hexamer stabilization. The presence of this mutant structure provides further evidence for hexameric annexin XII, and possible in vivo roles are discussed.

Annexins V and XII insert into bilayers at mildly acidic pH and form ion channels.

The functional hallmark of annexins is the ability to bind to the surface of phospholipid membranes in a reversible, Ca(2+)-dependent manner. We now report that human annexin V and hydra annexin XII reversibly bound to phospholipid vesicles in the absence of Ca(2+) at low pH; half-maximal vesicle association occurred at pH 5.3 and 5. 8, respectively. The following biochemical data support the hypothesis that these annexins insert into bilayers at mildly acidic pH. First, a photoactivatable reagent (3-trifluoromethyl)-3-(m-[(125)I]iodophenyl)diazirine) which selectively labels proteins exposed to the hydrophobic domain of bilayers reacted with these annexins at pH 5.0 and below but not at neutral pH. Second, in a Triton X-114 partitioning assay, annexins V and XII act as integral membrane proteins at low pH and as hydrophilic proteins at neutral pH; in the presence of phospholipids half-maximal partitioning into detergent occurred at pH approximately 5.0. Finally, annexin V or XII formed single channels in phospholipid bilayers at low pH but not at neutral pH. A model is discussed in which the concentrations of H(+) and Ca(2+) regulate the reversible conversion of three forms of annexins-soluble, peripheral membrane, and transmembrane.

Structural changes in bacteriorhodopsin during ion transport at 2 angstrom resolution.

Crystal structures of the Asp96 to Asn mutant of the light-driven proton pump bacteriorhodopsin and its M photointermediate produced by illumination at ambient temperature have been determined to 1.8 and 2.0 angstroms resolution, respectively. The trapped photoproduct corresponds to the late M state in the transport cycle-that is, after proton transfer to Asp85 and release of a proton to the extracellular membrane surface, but before reprotonation of the deprotonated retinal Schiff base. Its density map describes displacements of side chains near the retinal induced by its photoisomerization to 13-cis,15-anti and an extensive rearrangement of the three-dimensional network of hydrogen-bonded residues and bound water that accounts for the changed pKa values (where Ka is the acid constant) of the Schiff base and Asp85. The structural changes detected suggest the means for conserving energy at the active site and for ensuring the directionality of proton translocation.

Structure of bacteriorhodopsin at 1.55 A resolution.

Th?e atomic structure of the light-driven ion pump bacteriorhodopsin and the surrounding lipid matrix was determined by X-ray diffraction of crystals grown in cubic lipid phase. In the extracellular region, an extensive three-dimensional hydrogen-bonded network of protein residues and seven water molecules leads from the buried retinal Schiff base and the proton acceptor Asp85 to the membrane surface. Near Lys216 where the retinal binds, transmembrane helix G contains a pi-bulge that causes a non-proline? kink. The bulge is stabilized by hydrogen-bonding of the main-chain carbonyl groups of Ala215 and Lys216 with two buried water molecules located between the Schiff base and the proton donor Asp96 in the cytoplasmic region. The results indicate extensive involvement of bound water molecules in both the structure and the function of this seven-helical membrane protein. A bilayer of 18 tightly bound lipid chains forms an annulus around the protein in the crystal. Contacts between the trimers in the membrane plane are mediated almost exclusively by lipids.