Glial activation in white matter following ischemia in the neonatal P7 rat brain

This study examines cell death and proliferation in the white matter after neonatal stroke. In post-natal day 7 injured rat, there was a marked reduction in myelin basic protein (MBP) immunostaining mainly corresponding to numerous pyknotic immature oligodendrocytes and TUNEL-positive astrocytes in the ipsilateral external capsule. In contrast, a substantial restoration of MBP, as indicated by the MBP ratio of left-toright, occurred in the cingulum at 48 (1.27 +- 0.12) and 72 (1.30 +- 0.18, p<0.05) hours of recovery as compared to age-matched controls (1.03 +- 0.14). Ki-67 immunostaining revealed a first peak of newly-generated cells in the dorsolateral hippocampal subventricular zone and cingulum at 72 hours after reperfusion. Double immunofluorescence revealed that most of the Ki-67-positive cells were astrocytes at 48 hours and NG2 pre-oligodendrocytes at 72 hours of recovery. Microglia infiltration occurs over several days in the cingulum and a huge quantity of macrophages reached the subcortical white matter where they engulfed immature oligodendrocytes. The overall results suggest that the persistent activation of microglia involves a chronic component of immunoinflammation, which overwhelms repair processes and contributes to cystic growth in the developing brain.Comment: 30 page

Induction of early Purkinje cell dendritic differentiation by thyroid hormone requires RORα

<p>Abstract</p> <p>Background</p> <p>The active form (T₃) of thyroid hormone (TH) controls critical aspects of cerebellar development, such as migration of postmitotic neurons and terminal dendritic differentiation of Purkinje cells. The effects of T₃on early dendritic differentiation are poorly understood.</p> <p>Results</p> <p>In this study, we have analyzed the influence of T₃on the progression of the early steps of Purkinje cell dendritic differentiation in postnatal day 0 organotypic cerebellar cultures. These steps include, successively, regression of immature neuritic processes, a stellate cell stage, and the extension of several long and mature perisomatic protrusions before the growth of the ultimate dendritic tree. We also studied the involvement of RORα, a nuclear receptor controlling early Purkinje cell dendritic differentiation. We show that T₃treatment leads to an accelerated progression of the early steps of dendritic differentiation in culture, together with an increased expression of RORα (mRNA and protein) in both Purkinje cells and interneurons. Finally, we show that T₃failed to promote early dendritic differentiation in <it>staggerer </it>RORα-deficient Purkinje cells.</p> <p>Conclusions</p> <p>Our results demonstrate that T₃action on the early Purkinje cell dendritic differentiation process is mediated by RORα.</p

Reinnervation of late postnatal purkinje cells by climbing fibers: neosynaptogenesis without transient multi-innervation.

Synaptic partner selection and refinement of projections are important in the development of precise and functional neuronal connections. We investigated the formation of new synaptic connections in a relatively mature system to test whether developmental events can be recapitulated at later stages (i.e., after the mature synaptic organization has been established), using a model of postlesional reinnervation in the olivo-cerebellar pathway. During the development of this pathway, synaptic connections between climbing fibers (CFs) and Purkinje cells (PCs) are diffuse and redundant before synapse elimination refines the pattern. The regression of CFs during the first 2 postnatal weeks in the rat leads to mono-innervation of each PC. After unilateral transection of the rat olivo-cerebellar pathway and intracerebellar injection of BDNF 24 h after lesion, axons from the remaining inferior olive can sprout into the deafferented hemicerebellum and establish new contacts with denervated PCs at later developmental stages. We found that these contacts are first established on somatic thorns before the CFs translocate to the PC dendrites, recapitulating the morphological steps of normal CF-PC synaptogenesis, but on a relatively mature PC. However, electrophysiology of PC reinnervation by transcommissural CFs in these animals showed that each PC is reinnervated by only one CF. This mono-innervation contrasts with the reinnervation of grafted immature PCs in the same cerebellum. Our results provide evidence that relatively mature PCs do not receive several olivary afferents during late reinnervation, suggesting a critical role of the target cell state in the control of CF-PC synaptogenesis. Thus, synapse exuberance and subsequent elimination are not a prerequisite to reach a mature relationship between synaptic partners

Off-line and On-line Power Dispatching Strategies for a Grid Connected Commercial Building with Storage Unit

With the development of decentralized power sources based on renewable energy, power grids need smarter operations to be run properly. This paper refers to a microgrid with solar panels associated with an energy storage unit connected to the main grid. An off-line optimal dispatching of the storage power flows is proposed in order to minimize energy costs with regards to the daily energy rates. An on-line management strategy is also introduced so as to control in real-time the grid power predicted over the day by the off-line dispatching

Identification of platelet hyper-reactivity measured with a portable device immediately after percutaneous coronary intervention predicts in stent thrombosis

Introduction: Platelet hyper-reactivity, despite a standard anti-thrombotic therapy, is a recognized risk factor for recurrent myocardial ischemia and in-stent thrombosis following PCI. We have investigated whether this detrimental condition, measured by collagen-epinephrine closure times (CEPI-CT) with the Platelet Function Analyzer (PFA-100) device could predict IST defined as the composite of cardiovascular death or myocardial infarction. Materials and methods: CEPI-CT was measured in 256 consecutive patients with stable angina (n=103) or ACS (n=153) 30?8 h after PCI (T0) and 1 month later (T1). All patients were followed up for a mean period of 9 months. Platelet hyperactivity was defined as a CEPI-CTb190 s. Results: Baseline CEPI-CTb190 s was associated with a higher rate of death or MI (LogRank &#967;2 =4.23, p=0.039) as compared with CEPI-CTN190 s (4.6% vs. 0.7%). Multivariable analysis after adjustment for other risk factors confirmed that baseline CEPI-CTb190 s was an independent correlate for death or MI (Hazard ratio 6.981, p=0.008). At T1 there was a significant prolongati

Identification of genes involved in ceramide-dependent neuronal apoptosis using cDNA arrays

BACKGROUND: Ceramide is important in many cell responses, such as proliferation, differentiation, growth arrest and apoptosis. Elevated ceramide levels have been shown to induce apoptosis in primary neuronal cultures and neuronally differentiated PC 12 cells. RESULTS: To investigate gene expression during ceramide-dependent apoptosis, we carried out a global study of gene expression in neuronally differentiated PC 12 cells treated with C(2)-ceramide using an array of 9,120 cDNA clones. Although the criteria adopted for differential hybridization were stringent, modulation of expression of 239 genes was identified during the effector phase of C(2)-ceramide-induced cell death. We have made an attempt at classifying these genes on the basis of their putative functions, first with respect to known effects of ceramide or ceramide-mediated transduction systems, and then with respect to regulation of cell growth and apoptosis. CONCLUSIONS: Our cell-culture model has enabled us to establish a profile of gene expression during the effector phase of ceramide-mediated cell death. Of the 239 genes that met the criteria for differential hybridization, 10 correspond to genes previously involved in C(2)-ceramide or TNF-α signaling pathways and 20 in neuronal disorders, oncogenesis or more broadly in the regulation of proliferation. The remaining 209 genes, with or without known functions, constitute a pool of genes potentially implicated in the regulation of neuronal cell death