Current evidence suggests that delta oscillations (0.5-4 Hz) in the brain are generated by intrinsic network mechanisms involving cortical and thalamic circuits. Here we report that delta band ...oscillation in spike and local field potential (LFP) activity in the whisker barrel cortex of awake mice is phase locked to respiration. Furthermore, LFP oscillations in the gamma frequency band (30-80 Hz) are amplitude modulated in phase with the respiratory rhythm. Removal of the olfactory bulb eliminates respiration-locked delta oscillations and delta-gamma phase-amplitude coupling. Our findings thus suggest respiration-locked olfactory bulb activity as a main driving force behind delta oscillations and gamma power modulation in the whisker barrel cortex in the awake state.
Maintaining carotid patency and avoiding symptomatic intracranial hemorrhage are competing concerns in tandem occlusions. This study provides data regarding the safety and efficacy of eptifibatide in ...stroke from tandem occlusion of the extracranial carotid artery and the intracranial carotid or middle cerebral artery.
This is a retrospective analysis of 58 consecutive patients who received low-dose eptifibatide (135-mcg/kg bolus, 1-mcg/kg/min infusion) during treatment of tandem occlusions. Brain imaging and carotid sonography were performed at 24-36 hours. mRS was documented at 90 days, and carotid sonography, at 30-60 days.
The median age and NIHSS score were 64 years and 15, respectively. Twenty-five patients (43%) received tPA. ASPECTSs were 8-10 in 47 (81%) and 5-7 in 11 (19%) patients. Thirty-eight patients had angioplasty/stent placement acutely; 20 had angioplasty alone. Symptomatic intracranial hemorrhage occurred in 1 patient (2%). TICI 2b or higher was achieved in 56 patients (96%). Fifty-seven of 58 patients had clinical follow-up at 90 days (1 lost to follow up). The 90-day mRS was 0-2 in 42 patients (72%). There were 4/58 (7%) re-occlusions within 24-36 hours, all originally treated with stent placement. Forty-nine of 53 surviving patients had carotid sonography at 30-60 days, with 3 delayed re-occlusions, 2 with stents and 1 with angioplasty alone. The overall carotid patency at 30-60 days was 42/49 (86%). Carotid re-occlusion was not associated with clinical decline.
Low-dose eptifibatide seemed to be safe in tandem occlusions (symptomatic intracranial hemorrhage, 2%), although asymptomatic cervical carotid artery re-occlusions still occurred in 14% of patients.
Reversible vasoconstriction syndrome is a complex of clinical symptoms and angiographic findings, which, while having a mostly benign clinical course, has clinical and imaging overlap with more ...serious disorders such as vasculitis and aneurysmal SAH and itself includes a minority of patients with fulminant vasoconstriction resulting in severe intracranial complications. Endovascular options for patients with refractory reversible cerebral vasoconstriction syndrome include intra-arterial vasodilator infusion similar to therapy for patients with vasospasm after SAH. To date, only case reports and 1 small series have discussed the utility of intra-arterial vasodilators for the treatment of reversible cerebral vasoconstriction syndrome. We report an additional series of 11 medically refractory cases of presumed or proved reversible cerebral vasoconstriction syndrome successfully treated with intra-arterial verapamil infusion. Furthermore, we propose that the reversal of vasoconstriction, as seen on angiography, could fulfill a diagnostic criterion.
We report the observation of a steepening in the cosmic ray energy spectrum of heavy primary particles at about 8×10(16) eV. This structure is also seen in the all-particle energy spectrum, but is ...less significant. Whereas the "knee" of the cosmic ray spectrum at 3-5×10(15) eV was assigned to light primary masses by the KASCADE experiment, the new structure found by the KASCADE-Grande experiment is caused by heavy primaries. The result is obtained by independent measurements of the charged particle and muon components of the secondary particles of extensive air showers in the primary energy range of 10(16) to 10(18) eV. The data are analyzed on a single-event basis taking into account also the correlation of the two observables.
Central nervous system infections can underlie the development of epilepsy, and Theiler's murine encephalomyelitis virus (TMEV) infection in C57BL/6J mice provides a novel model of infection-induced ...epilepsy. Approximately 50-65% of infected mice develop acute, handling-induced seizures during the infection. Brains display acute neuropathology, and a high number of mice develop spontaneous, recurrent seizures and behavioral comorbidities weeks later. This study characterized the utility of this model for drug testing by assessing whether antiseizure drug treatment during the acute infection period attenuates handling-induced seizures, and whether such treatment modifies associated comorbidities. Male C57BL/6J mice infected with TMEV received twice-daily valproic acid (VPA; 200 mg/kg), carbamazepine (CBZ; 20 mg/kg), or vehicle during the infection (days 0-7). Mice were assessed twice daily during the infection period for handling-induced seizures. Relative to vehicle-treated mice, more CBZ-treated mice presented with acute seizures; VPA conferred no change. In mice displaying seizures, VPA, but not CBZ, reduced seizure burden. Animals were then randomly assigned to acute and long-term follow-up. VPA was associated with significant elevations in acute (day 8) glial fibrillary acidic protein (astrocytes) immunoreactivity, but did not affect NeuN (neurons) immunoreactivity. Additionally, VPA-treated mice showed improved motor performance 15 days postinfection (DPI). At 36 DPI, CBZ-treated mice traveled significantly less distance through the center of an open field, indicative of anxiety-like behavior. CBZ-treated mice also presented with significant astrogliosis 36 DPI. Neither CBZ nor VPA prevented long-term reductions in NeuN immunoreactivity. The TMEV model thus provides an etiologically relevant platform to evaluate potential treatments for acute seizures and disease modification.
► All-particle energy spectrum of cosmic rays between knee and ankle is not a single power law. ► Just above 1016eV the spectrum exhibits a hardening. ► Around 8×1016eV there is a knee-like feature ...in the spectrum.
The energy spectrum of cosmic rays between 1016eV and 1018eV, derived from measurements of the shower size (total number of charged particles) and the total muon number of extensive air showers by the KASCADE-Grande experiment, is described. The resulting all-particle energy spectrum exhibits strong hints for a hardening of the spectrum at approximately 2·1016eV and a significant steepening at ≈8·1016eV. These observations challenge the view that the spectrum is a single power law between knee and ankle. Possible scenarios generating such features are discussed in terms of astrophysical processes that may explain the transition region from galactic to extragalactic origin of cosmic rays.
Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for ...therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate here that chronic treatment with a proprietary Hsp90 inhibitor compound (OS47720) not only elicits a heat-shock-like response but also offers synaptic protection in symptomatic Tg2576 mice, a model of Alzheimer's disease, without noticeable systemic toxicity. Despite a short half-life of OS47720 in mouse brain, a single intraperitoneal injection induces rapid and long-lasting (>3 days) nuclear activation of the heat-shock factor, HSF1. Mechanistic study indicates that the remedial effects of OS47720 depend upon HSF1 activation and the subsequent HSF1-mediated transcriptional events on synaptic genes. Taken together, this work reveals a novel role of HSF1 in synaptic function and memory, which likely occurs through modulation of the synaptic transcriptome.
An efficient scheme for one-dimensional extensive air shower simulation and its implementation in the program
conex are presented. Explicit Monte Carlo simulation of the high-energy part of hadronic ...and electro-magnetic cascades in the atmosphere is combined with a numeric solution of cascade equations for smaller energy sub-showers to obtain accurate shower predictions. The developed scheme allows us to calculate not only observables related to the number of particles (shower size) but also ionization energy deposit profiles which are needed for the interpretation of data of experiments employing the fluorescence light technique. We discuss in detail the basic algorithms developed and illustrate the power of the method. It is shown that Monte Carlo, numerical, and hybrid air shower calculations give consistent results which agree very well with those obtained within the
corsika program.
In trained reaching rats, we recorded simple spikes of pairs of Purkinje cells that, with respect to each other, were either aligned on a beam of shared parallel fibers or instead were located off ...beam. Rates of simple spike firing in both on-beam and off-beam Purkinje cell pairs commonly showed great variety in depth of modulation during reaching behavior. But with respect to timing, on-beam Purkinje cell pairs had simple spikes that were tightly time-locked to each other (either delayed or simultaneous) and to movement, despite the variability in rate. By contrast, off-beam Purkinje cell pairs had simple spikes that were not time-locked to each other, neither delayed nor simultaneous. We discuss the implications of these observations for the cerebellar role in timing and coordinating movement.
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