Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity

The promotion of post-ischaemic motor recovery remains a major challenge in clinical neurology. Recently, plasticity-promoting effects have been described for the growth factor erythropoietin in animal models of neurodegenerative diseases. To elucidate erythropoietin's effects in the post-acute ischaemic brain, we examined how this growth factor influences functional neurological recovery, perilesional tissue remodelling and axonal sprouting of the corticorubral and corticobulbar tracts, when administered intra-cerebroventricularly starting 3 days after 30 min of middle cerebral artery occlusion. Erythropoietin administered at 10 IU/day (but not at 1 IU/day), increased grip strength of the contralesional paretic forelimb and improved motor coordination without influencing spontaneous locomotor activity and exploration behaviour. Neurological recovery by erythropoietin was associated with structural remodelling of ischaemic brain tissue, reflected by enhanced neuronal survival, increased angiogenesis and decreased reactive astrogliosis that resulted in reduced scar formation. Enhanced axonal sprouting from the ipsilesional pyramidal tract into the brainstem was observed in vehicle-treated ischaemic compared with non-ischaemic animals, as shown by injection of dextran amines into both motor cortices. Despite successful remodelling of the perilesional tissue, erythropoietin enhanced axonal sprouting of the contralesional, but not ipsilesional pyramidal tract at the level of the red and facial nuclei. Moreover, molecular biological and histochemical studies revealed broad anti-inflammatory effects of erythropoietin in both hemispheres together with expression changes of plasticity-related molecules that facilitated contralesional axonal growth. Our study establishes a plasticity-promoting effect of erythropoietin after stroke, indicating that erythropoietin acts via recruitment of contralesional rather than of ipsilesional pyramidal tract projection

Protein phosphatase 1-dependent bidirectional synaptic plasticity controls ischemic recovery in the adult brain

Protein kinases and phosphatases can alter the impact of excitotoxicity resulting from ischemia by concurrently modulating apoptotic/survival pathways. Here, we show that protein phosphatase 1 (PP1), known to constrain neuronal signaling and synaptic strength (Mansuy et al., 1998; Morishita et al., 2001), critically regulates neuroprotective pathways in the adult brain. When PP1 is inhibited pharmacologically or genetically, recovery from oxygen/glucose deprivation (OGD) in vitro, or ischemia in vivo is impaired. Furthermore, in vitro, inducing LTP shortly before OGD similarly impairs recovery, an effect that correlates with strong PP1 inhibition. Conversely, inducing LTD before OGD elicits full recovery by preserving PP1 activity, an effect that is abolished by PP1 inhibition. The mechanisms of action of PP1 appear to be coupled with several components of apoptotic pathways, in particular ERK1/2 (extracellular signal-regulated kinase 1/2) whose activation is increased by PP1 inhibition both in vitro and in vivo. Together, these results reveal that the mechanisms of recovery in the adult brain critically involve PP1, and highlight a novel physiological function for long-term potentiation and long-term depression in the control of brain damage and repair

Unilateral Spinal Anaesthesia in Calves

ΔΕΝ ΔΙΑΤΙΘΕΤΑΙ ΕΡΙΛΗΨΗIn this study, we aimed to evaluate the effects of unilateral anaesthesia by the administration of hyperbaric bupivacaine through the lumbosacral space into the subarachnoid space in calves. A total of 10 calves with unilateral femoral fractures were included in the study. After each calf was placed in a lateral position on the side intended for surgery, 15 mg of hyperbaric bupivacaine was slowly injected into the subarachnoid space. The onset, duration and depth of anaesthesia were determined by the pinprick test (scale 1–4). In addition, heart rate, diastolic arterial blood pressure, systolic arterial blood pressure, mean arterial blood pressure, respiratory rate and body temperature of the calves were monitored and recorded from the onset to 120 min after anaesthesia. The onset of unilateral spinal anaesthesia was within 20 s and the mean duration of anaesthesia was 155.40 min. Although there were statistical differences between hemodynamic values in the study, they were within the reference values. As a result, we believe that unilateral spinal anaesthesia in calves provides adequate anaesthesia for use in orthopaedic procedures; thus, it can be used in practice

The Mystery Deepens: Spitzer Observations of Cool White Dwarfs

We present 4.5$\mu$m and 8$\mu$m photometric observations of 18 cool white dwarfs obtained with the Spitzer Space Telescope. Our observations demonstrate that four white dwarfs with T_eff< 6000 K show slightly depressed mid-infrared fluxes relative to white dwarf models. In addition, another white dwarf with a peculiar optical and near-infrared spectral energy distribution (LHS 1126) is found to display significant flux deficits in Spitzer observations. These mid-infrared flux deficits are not predicted by the current white dwarf models including collision induced absorption due to molecular hydrogen. We postulate that either the collision induced absorption calculations are incomplete or there are other unrecognized physical processes occuring in cool white dwarf atmospheres. The spectral energy distribution of LHS 1126 surprisingly fits a Rayleigh-Jeans spectrum in the infrared, mimicking a hot white dwarf with effective temperature well in excess of 10$^5$ K. This implies that the source of this flux deficit is probably not molecular absorption but some other process.Comment: 17 pages, 4 figures, ApJ in press, 10 May 200

METU interoperable database system

and Sevgi Foundation, Turkey) is a multidatabase system based on OMG&apos;s (OMG is a registered trademark, and CORBA, ORB, OMG IDL, Object Request Broker are trademarks of OMG) distributed object management architecture. It is implemented on top of a CORBA compliant ORB, namely, DEC&apos;s ObjectBroker (ObjectBroker is a registered trademark of DEC Corp.) [DDO96]. In MIND all local databases are encapsulated in generic Database Object. The interface of the generic Database Object is de ned in CORBA IDL and multiple implementations of this interface, one for each component DBMSs, namely, Oracle7 (Oracle7 is a trademark of Oracle Corp.), Sybase (Sybase is a trademark of Sybase Corp.), Adabas D (Adabas D is a trademark of Software AG Corp.) and MOOD [Dog94] are provided. MIND provides its users a common data model and a single global query language based on SQL. The main functionalities of MIND are global query processing, global transaction management and schema integration. The basic component classes in the system are

Designing Excited States: Theory-Guided Access to Efficient Photosensitizers for Photodynamic Action

Cataloged from PDF version of article.The in silico design of tetraradical S 1 states was validated experimentally through synthesis, followed by characterization including phosphorescence measurements, use of trap molecules, and cell culture studies, leading to a series of orthogonal dimers of Bodipy chromophores with remarkable singlet oxygen efficiencies (see picture). A new path for the rational development of efficient photosensitizers is thus revealed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Cyclosporin A treatment in severe childhood psoriasis

Though used occasionally, systemic therapies in severe childhood psoriasis have not been systematically investigated. Cyclosporin A (CysA) is effective in adults with severe psoriasis but there are no extensive data regarding the efficacy and safety of its use in childhood psoriasis. In this paper, we describe six children aged between 11 months and 13 years (average: 7.6 years) treated with CysA microemulsion formulation for severe psoriasis, who had been unresponsive to other treatments. The CysA dose ranged from 2 to 4 mg/kg/day, for periods varying from 8 to 105 weeks (mean: 54 weeks). Dose tapering was gradual after lesion improvement and adjusted according to clinical response. Adjuvant therapy with topical steroids, vitamin D3 ointments, coal tar preparations or anthralin was used in all children. Acitretin was used in three patients for short periods. The children were regularly monitored for serum renal and liver function and blood pressure. Improvement of skin lesions was achieved after between 4 and 30 (mean: 12) weeks of treatment, with complete remission in three children. Relapse of lesions occurred in the other children during CysA reduction, but they responded to a dose increase. The treatment was found to be well tolerated and with no significant side-effects. CysA can be used in carefully selected and monitored patients and may represent an alternative tool for severe episodes of psoriasis in children, when other therapies are unsuccessful

Theoretical investigation of InAs/GaSb type-II pin superlattice infrared detector in the mid wavelength infrared range

In this study, we present the theoretical investigation of type-II InAs/GaSb superlattice p-i-n detector. Kronig-Penney and envelope function approximation is used to calculate band gap energy and superlattice minibands. Variational method is also used to calculate exciton binding energies. Our results show that carriers overlap increases at GaSb/InAs interface on the higher energy side while it decreases at InAs/GaSb interface on the lower energy side with increasing reverse bias due to shifting the hole wavefunction toward to the GaSb/InAs interface decisively. Binding energies increase with increasing electric field due to overall overlap of electron and hole wave functions at the both interfaces in contrast with type I superlattices. This predicts that optical absorption is enhanced with increasing electric field. © 2013 American Institute of Physics