Occupational performance one to five years after aneurysmal subarachnoid haemorrhage: a cohort study.

OBJECTIVE: To report on the self-perceived occupational performance of patients with aneurysmal subarachnoid haemorrhage and examine the associations between aneurysmal subarachnoid haemorrhage characteristics, socio-demographic factors and self-perceived problems. DESIGN: A single-centre cohort study design was combined with a cross-sectional analysis. SUBJECTS/PATIENTS: All patients with aneurysmal subarachnoid haemorrhage who were capable of performing activities of daily living before discharge from hospital were included. METHODS: The assessment of the patient's occupational performance followed a patient-reported outcome measure 1 to 5 years after the subarachnoid haemorrhage. Secondary outcomes comprised scores from the Glasgow Outcome Scale, modified Rankin Scale, Fisher Scale, World Federation of Neurological Societies grading system, vasospasm, and hydrocephalus. RESULTS: Of the 62 patients included in the study (66% female, mean age 55 years), 79% reported experiencing issues with occupational performance, most frequently with regard to leisure and productivity. The problems reported were significantly associated with vasospasm (p = 0.021) and the Glasgow Outcome Scale score (p = 0.045). CONCLUSION: Even patients who have had aneurysmal subarachnoid haemorrhage with a favourable outcome may encounter occupational performance difficulties for several years. It is vital to use patient-reported outcome measures to identify these issues. This research enhances our comprehension of aneurysmal subarachnoid haemorrhage patients' self-perceived occupational performance and the factors that affect their performance.

Endovascular Treatment of Dural Arteriovenous Fistulas in a Medium-Sized Scandinavian Neurovascular Center.

BACKGROUND: Endovascular treatment is the primary treatment modality for dural arteriovenous fistulas (DAVFs). We performed a retrospective analysis of DAVFs treated in our hospital to determine if high-quality endovascular treatment can be provided in a medium-volume vascular center. METHODS: From 2007 to 2021, 69 DAVF treatments were undertaken in our hospital. Of these DAVFs, 55 were endovascular, 11 were open surgical procedures, and 3 were Gamma Knife treatments. Of the endovascular treatments, 10 (18.2%) were in ruptured DAVFs. The most common location of endovascularly treated DAVFs was at the transverse/sigmoid sinus (32.7%) and at the cavernous sinus (25.5%). Of the endovascularly treated DAVFs, 38.2% were low-grade fistulas (Cognard I/IIa), whereas 61.8% were high-grade fistulas (Cognard ≥IIb). 58.2% of fistulas were treated transarterially. DAVFs located in the cavernous sinus were treated using coils alone, whereas most other DAVFs were treated with liquid embolics alone or in combination with coils. RESULTS: Complete or near-complete cure was achieved in 74.5% of treatments, whereas 18.2% of treatments resulted in downgrading of the fistula. Twelve patients were retreated once (9 endovascularly) and 1 patient was retreated twice. After retreatment, complete or near-complete cure was achieved in 86.4% of patients. 72.7% of treatments were performed without any remnant or retreatment. There were no procedure-related deaths. One patient experienced a complication resulting in permanent neurologic deficits. Seven other complications (12.7%) were recorded, all asymptomatic or causing only temporary symptoms. CONCLUSIONS: Based on our findings, we conclude that high-quality treatment of DAVFs can be provided in a medium-volume vascular center.

AMPA receptors at ribbon synapses in the mammalian retina: kinetic models and molecular identity.

In chemical synapses, neurotransmitter molecules released from presynaptic vesicles activate populations of postsynaptic receptors that vary in functional properties depending on their subunit composition. Differential expression and localization of specific receptor subunits are thought to play fundamental roles in signal processing, but our understanding of how that expression is adapted to the signal processing in individual synapses and microcircuits is limited. At ribbon synapses, glutamate release is independent of action potentials and characterized by a high and rapidly changing rate of release. Adequately translating such presynaptic signals into postsynaptic electrical signals poses a considerable challenge for the receptor channels in these synapses. Here, we investigated the functional properties of AMPA receptors of AII amacrine cells in rat retina that receive input at spatially segregated ribbon synapses from OFF-cone and rod bipolar cells. Using patch-clamp recording from outside-out patches, we measured the concentration dependence of response amplitude and steady-state desensitization, the single-channel conductance and the maximum open probability. The GluA4 subunit seems critical for the functional properties of AMPA receptors in AII amacrines and immunocytochemical labeling suggested that GluA4 is located at synapses made by both OFF-cone bipolar cells and rod bipolar cells. Finally, we used a series of experimental observables to develop kinetic models for AII amacrine AMPA receptors and subsequently used the models to explore the behavior of the receptors and responses generated by glutamate concentration profiles mimicking those occurring in synapses. These models will facilitate future in silico modeling of synaptic signaling and processing in AII amacrine cells.

Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma.

L-Glutamine (Gln) functions physiologically to balance the carbon and nitrogen requirements of tissues. It has been proposed that in cancer cells undergoing aerobic glycolysis, accelerated anabolism is sustained by Gln-derived carbons, which replenish the tricarboxylic acid (TCA) cycle (anaplerosis). However, it is shown here that in glioblastoma (GBM) cells, almost half of the Gln-derived glutamate (Glu) is secreted and does not enter the TCA cycle, and that inhibiting glutaminolysis does not affect cell proliferation. Moreover, Gln-starved cells are not rescued by TCA cycle replenishment. Instead, the conversion of Glu to Gln by glutamine synthetase (GS; cataplerosis) confers Gln prototrophy, and fuels de novo purine biosynthesis. In both orthotopic GBM models and in patients, (13)C-glucose tracing showed that GS produces Gln from TCA-cycle-derived carbons. Finally, the Gln required for the growth of GBM tumours is contributed only marginally by the circulation, and is mainly either autonomously synthesized by GS-positive glioma cells, or supplied by astrocytes.

Properties of glycine receptors underlying synaptic currents in presynaptic axon terminals of rod bipolar cells in the rat retina.

The excitability of presynaptic terminals can be controlled by synaptic input that directly targets the terminals. Retinal rod bipolar axon terminals receive presynaptic input from different types of amacrine cells, some of which are glycinergic. Here, we have performed patch-clamp recordings from rod bipolar axon terminals in rat retinal slices. We used whole-cell recordings to study glycinergic inhibitory postsynaptic currents (IPSCs) under conditions of adequate local voltage clamp and outside-out patch recordings to study biophysical and pharmacological properties of the glycine receptors with ultrafast application. Glycinergic IPSCs, recorded in both intact cells and isolated terminals, were strychnine sensitive and displayed fast kinetics with a double-exponential decay. Ultrafast application of brief (approximately 1 ms) pulses of glycine (3 mM) to patches evoked responses with fast, double-exponential deactivation kinetics, no evidence of desensitization in double-pulse experiments, relatively low apparent affinity (EC(50) approximately 100 microM), and high maximum open probability (0.9). Longer pulses evoked slow, double-exponential desensitization and double-pulse experiments indicated slow, double-exponential recovery from desensitization. Non-stationary noise analysis of IPSCs and patch responses yielded single-channel conductances of approximately 41 pS and approximately 64 pS, respectively. Directly observed single-channel gating occurred at approximately 40-50 pS and approximately 80-90 pS in both types of responses, suggesting a mixture of heteromeric and homomeric receptors. Synaptic release of glycine leads to transient receptor activation, with about eight receptors available to bind transmitter after release of a single vesicle. With a low intracellular chloride concentration, this leads to either hyperpolarizing or shunting inhibition that will counteract passive and regenerative depolarization and depolarization-evoked transmitter release.

Patch-clamp investigations and compartmental modeling of rod bipolar axon terminals in an in vitro thin-slice preparation of the mammalian retina.

To extend the usefulness of rod bipolar cells for studies of chemical synaptic transmission, we have performed electrophysiological recordings from rod bipolar axon terminals in an in vitro slice preparation of the rat retina. Whole cell recordings from axon terminals and cell bodies were used to investigate the passive membrane properties of rod bipolar cells and analyzed with a two-compartment equivalent electrical circuit model developed by Mennerick et al. For both terminal- and soma-end recordings, capacitive current decays were well fitted by biexponential functions. Computer simulations of simplified models of rod bipolar cells demonstrated that estimates of the capacitance of the axon terminal compartment can depend critically on the recording location, with terminal-end recordings giving the best estimates. Computer simulations and whole cell recordings demonstrated that terminal-end recordings can yield more accurate estimates of the peak amplitude and kinetic properties of postsynaptic currents generated at the axon terminals due to increased electrotonic filtering of these currents when recorded at the soma. Finally, we present whole cell and outside-out patch recordings from axon terminals with responses evoked by GABA and glycine, spontaneous inhibitory postsynaptic currents, voltage-gated Ca(2+) currents, and depolarization-evoked reciprocal synaptic responses, verifying that the recorded axon terminals are involved in normal pre- and postsynaptic relationships. These results demonstrate that axon terminals of rod bipolar cells are directly accessible to whole cell and outside-out patch recordings, extending the usefulness of this preparation for detailed studies of pre- and postsynaptic mechanisms of synaptic transmission in the CNS.

Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling.

Whereas glutamate transporters in glial cells and postsynaptic neurons contribute significantly to re-uptake of synaptically released transmitter, the functional role of presynaptic glutamate transporters is poorly understood. Here, we used electrophysiological recording to examine the functional properties of a presynaptic glutamate transporter in rat retinal rod bipolar cells and its role in regulating glutamatergic synaptic transmission between rod bipolar cells and amacrine cells. Release of glutamate activated the presynaptic transporter with a time course that suggested a perisynaptic localization. The transporter was also activated by spillover of glutamate from neighboring rod bipolar cells. By recording from pairs of rod bipolar cells and AII amacrine cells, we demonstrate that activation of the transporter-associated anion current hyperpolarizes the presynaptic terminal and thereby inhibits synaptic transmission by suppressing transmitter release. Given the evidence for presynaptic glutamate transporters, similar mechanisms could be of general importance for transmission in the nervous system.

Functional properties of spontaneous EPSCs and non-NMDA receptors in rod amacrine (AII) cells in the rat retina.

The functional properties of spontaneous, glutamatergic EPSCs and non-NMDA receptors in AII amacrine cells were studied in whole cells and patches from slices of the rat retina using single and dual electrode voltage clamp recording. Pharmacological analysis verified that the EPSCs (Erev approximately 0 mV) were mediated exclusively by AMPA-type receptors. EPSCs displayed a wide range of waveforms, ranging from simple monophasic events to more complex multiphasic events. Amplitude distributions of EPSCs were moderately skewed towards larger amplitudes (modal peak 23 pA). Interevent interval histograms were best fitted with a double exponential function. Monophasic, monotonically rising EPSCs displayed very fast kinetics with an average 10-90 % rise time of approximately 340 micro s and a decay phase well fitted by a single exponential (taudecay approximately 760 micro s). The specific AMPA receptor modulator cyclothiazide markedly slowed the decay phase of spontaneous EPSCs (taudecay approximately 3 ms). An increase in temperature decreased both 10-90 % rise time and taudecay with Q10 values of 1.3 and 1.5, respectively. The decay kinetics were slower at positive membrane potentials compared to negative membrane potentials (205 mV/e-fold change in taudecay). Step depolarization of individual presynaptic rod bipolar cells or OFF-cone bipolar cells evoked transient, CNQX-sensitive responses in AII amacrine cells with average peak amplitudes of approximately 330 pA. Ultrafast application of brief (approximately 1 ms) or long (approximately 500 ms) pulses of glutamate to outside-out patches evoked strongly desensitizing responses with very fast deactivation and desensitization kinetics, well fitted by single (taudecay approximately 1.1 ms) and double exponential (tau1 approximately 3.5 ms; tau2 approximately 21 ms) functions, respectively. Double-pulse experiments indicated fast recovery from desensitization (tau approximately 12.4 ms). Our results indicate that spontaneous, AMPA receptor-mediated EPSCs in AII amacrine cells have very fast, voltage-dependent kinetics that can be well accounted for by the kinetic properties of the AMPA receptors themselves

Functional characteristics of non-NMDA-type ionotropic glutamate receptor channels in AII amacrine cells in rat retina.

The properties of non-NMDA glutamate receptor channels in AII amacrine cells were studied by patch-clamp recording from rat retinal slices. Application of AMPA or kainate to intact cells evoked currents with no apparent desensitization (EC50 of 118 microM for AMPA and 169 microM for kainate). Application of AMPA to patches evoked desensitizing responses with an EC50 of 217 and 88 microM for the peak and steady-state responses, respectively. Kainate-evoked responses of patches displayed no desensitization (EC50 = 162 microM). Cyclothiazide strongly potentiated AMPA-evoked responses and the AMPA-receptor antagonist GYKI 53655 inhibited both AMPA- and kainate-evoked responses (IC50 = 0.5-1.7 microM). Pre-equilibration with GYKI 53655 completely blocked the response to kainate and pretreatment with concanavalin A did not unmask a response mediated by kainate receptors. AMPA- and kainate-evoked currents reversed close to 0 mV. AMPA-evoked peak and steady-state response components in patches displayed linear and outwardly rectifying I-V relations with an RI (ratio of the slope conductances at +40 mV and -60 mV) of 0.96 +/- 0.11 and 5.6 +/- 1.3, respectively. AMPA-evoked currents displayed a voltage-dependent relaxation after steps to positive or negative membrane potentials, indicating that the outward rectification of the steady-state response is caused by a voltage-dependent kinetic parameter of channel gating. Under bi-ionic conditions ([Ca2+](out) = 30 mM, [Cs+)(in) = 171 mM), the reversal potentials of AMPA- and kainate-evoked currents indicated channels with significant Ca2+ permeability (P(Ca)/P(Cs) = 1.9-2.1). Stationary noise analysis indicated that kainate activated channels with an apparent chord conductance of approximately 9 pS. Non-stationary noise analysis indicated that AMPA and glutamate activated channels with apparent chord conductances of approximately 9, approximately 15, approximately 23 and approximately 38 pS. Discrete single-channel gating corresponding to chord conductances of approximately 23 pS could be directly observed in some responses. Thus, our results indicate expression of high-affinity, voltage-sensitive AMPA receptors with significant Ca2+ permeability and relatively large single-channel chord conductances in AII amacrine cells.