The chemokine CX3CL1 and its receptor CX3CR1 are constitutively expressed in the nervous system. In this study, we used in vivo murine models of permanent middle cerebral artery occlusion (pMCAO) to investigate the protective potential of CX3CL1. We report that exogenous CX3CL1 reduced ischemia-induced cerebral infarct size, neurological deficits, and caspase-3 activation. CX3CL1-induced neuroprotective effects were long lasting, being observed up to 50 d after pMCAO in rats. The neuroprotective action of CX3CL1 in different models of brain injuries is mediated by its inhibitory activity on microglia and, in vitro, requires the activation of adenosine receptor 1 (A 1 R). We show that, in the presence of the A 1 R antagonist 1,3-dipropyl-8-cyclopentylxanthine and in A 1 R ؊/؊ mice, the neuroprotective effect of CX3CL1 on pMCAO was abolished, indicating the critical importance of the adenosine system in CX3CL1 protection also in vivo. In apparent contrast with the above reported data but in agreement with previous findings, cx3cl1 ؊/؊ and cx3cr1 GFP/GFP mice, respectively, deficient in CX3CL1 or CX3CR1, had less severe brain injury on pMCAO, and the administration of exogenous CX3CL1 increased brain damage in cx3cl1 ؊/؊ ischemic mice. We also report that CX3CL1 induced a different phagocytic activity in wild type and cx3cl1 ؊/؊ microglia in vitro during cotreatment with the medium conditioned by neurons damaged by oxygenglucose deprivation. Together, these data suggest that acute administration of CX3CL1 reduces ischemic damage via an adenosinedependent mechanism and that the absence of constitutive CX3CL1-CX3CR1 signaling changes the outcome of microglia-mediated effects during CX3CL1 administration to ischemic brain.
A one-pot, two-step colloidal strategy to prepare bimagnetic hybrid nanocrystals (HNCs), comprising size-tuned fcc FePt and inverse spinel cubic iron oxide domains epitaxially arranged in a heterodimer configuration, is described. The HNCs have been synthesized in a unique surfactant environment by temperature-driven sequential reactions, involving the homogeneous nucleation of FePt seeds and the subsequent heterogeneous growth of iron oxide. This self-regulated mechanism offers high versatility in the control of the geometric features of the resulting heterostructures, circumventing the use of more elaborate seeded growth techniques. It has been found that, as a consequence of the exchange coupling between the two materials, the HNCs exhibit tunable single-phase-like magnetic behavior, distinct from that of their individual components. In addition, the potential of the heterodimers as effective contrast agents for magnetic resonance imaging techniques has been examined.
Background The involvement of complement system in brain injury has been scarcely investigated. Here we document the pivotal role of mannose binding lectin (MBL), one of the recognition molecules of the lectin complement pathway, in brain ischemic injury. Methods and Results Focal cerebral ischemia was induced in mice (by permanent or transient middle cerebral artery occlusion) and rats (by 3-vessels occlusion). We first observed that MBL is deposited on ischemic vessels up to 48h after injury and that functional MBL/MASP2 complexes are increased. Next we demonstrated that: 1) MBL−/− mice are protected from both transient and permanent ischemic injury; 2) Polyman2, the newly synthesized mannosylated molecule selected for its binding to MBL, improves neurological deficits and infarct volume when given up to 24h after ischemia in mice; 3) anti-MBL-A antibody improves neurological deficits and infarct volume when given up to 18h after ischemia, as assessed following 28d in rats. Conclusions Our data show an important role for MBL in the pathogenesis of brain ischemic injury and provide a strong support to the concept that MBL inhibition may be a relevant therapeutic target in humans, one with a wide therapeutic window of application.
We investigate the time autocorrelation of the molecular magnetization M (t) for three classes of magnetic molecules (antiferromagnetic rings, grids and nanomagnets), in contact with the phonon heat bath. For all three classes, we find that the exponential decay of the fluctuations of M (t), associated with the irreversible exchange of energy with the heat bath, is characterized by a single characteristic time τ (T, B) for not too high temperature T and field B. This is reflected in a nearly single-lorentzian shape of the spectral density of the fluctuations. We show that such fluctuations are effectively probed by NMR, and that our theory explains the recent phenomenological observation by Baek et al. (PRB70, 134434) that the Larmor-frequency dependence of 1/T1 data in a large number of AFM rings fits to a single-lorentzian form.PACS numbers: 76.60. Es,75.60.Jk A central aspect of the physics of magnetic molecules is the way molecular observables, and particularly the magnetization M , are affected by interactions of the spins with other degrees of freedom. When the latter behave as a heat bath, they cause decoherence of the time evolution of molecular observables, usually leading to relaxation dynamics and exponential time-decay of equilibrium fluctuations. The understanding and characterization of relaxation mechanisms in crystals containing magnetic molecules is not only important for evident fundamental reasons, but also because relaxation and, more generally, decoherence, constitute a major obstacle in the envisaged technological applications of these molecules. In particular, relaxation of M through phonons sets an upper bound[1] to the temperature range in which nanomagnets could be used as classical bits in a memory. In the possible application of some molecules as elementary units (qubits) in quantum information processing (QIP)[2], energy dissipation from the qubits to the nuclear-spins heat bath is the main concern regarding the efficiency of quantum logical gates and the performance of the computation. In this work, we show that for three important classes of magnetic molecules (antiferromagnetic (AFM) rings, grids and nanomagnets), the exponential decay of the fluctuations of M (t) due to spin-phonon interactions is dominated by a single characteristic time τ (T, B) over a wide range of temperatures and applied fields. While this was already known for the long-time decay of M in nanomagnets, our results show that this applies to completely different classes of molecules, and holds on much shorter time-scales as well. Indeed, in the considered (T, B) regimes this single characteristic frequency λ 0 = 1/τ dominates the fluctuations spectrum to such a large extent that even experimental probes whose intrinsic frequency is very different from λ 0 will nevertheless detect mostly this single spectral contribution. In particular, we show that NMR measurements of the longitudinal nuclear relaxation rate 1/T 1 can be used as a direct probe of the fluctuations of M , and that experimental 1/T 1 data are ...
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