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  1. Article ; Online: Cellular and Molecular Mechanisms of R/S-Roscovitine and CDKs Related Inhibition under Both Focal and Global Cerebral Ischemia

    Lucas Le Roy / Anne Letondor / Cloé Le Roux / Ahmed Amara / Serge Timsit

    Cells, Vol 10, Iss 104, p

    A Focus on Neurovascular Unit and Immune Cells

    2021  Volume 104

    Abstract: Ischemic stroke is the second leading cause of death worldwide. Following ischemic stroke, Neurovascular Unit (NVU) inflammation and peripheral leucocytes infiltration are major contributors to the extension of brain lesions. For a long time restricted ... ...

    Abstract Ischemic stroke is the second leading cause of death worldwide. Following ischemic stroke, Neurovascular Unit (NVU) inflammation and peripheral leucocytes infiltration are major contributors to the extension of brain lesions. For a long time restricted to neurons, the 10 past years have shown the emergence of an increasing number of studies focusing on the role of Cyclin-Dependent Kinases (CDKs) on the other cells of NVU, as well as on the leucocytes. The most widely used CDKs inhibitor, ( R )-roscovitine, and its ( S ) isomer both decreased brain lesions in models of global and focal cerebral ischemia. We previously showed that ( S )-roscovitine acted, at least, by modulating NVU response to ischemia. Interestingly, roscovitine was shown to decrease leucocytes-mediated inflammation in several inflammatory models. Specific inhibition of roscovitine majors target CDK 1, 2, 5, 7, and 9 showed that these CDKs played key roles in inflammatory processes of NVU cells and leucocytes after brain lesions, including ischemic stroke. The data summarized here support the investigation of roscovitine as a potential therapeutic agent for the treatment of ischemic stroke, and provide an overview of CDK 1, 2, 5, 7, and 9 functions in brain cells and leucocytes during cerebral ischemia.
    Keywords ischemic stroke ; neurovascular unit ; leucocytes ; CDK ; roscovitine ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Gender difference of geographic distribution of the stroke incidence affected by socioeconomic, clinical and urban-rural factors

    Cindy M. Padilla / Anais Foucault / Olivier Grimaud / Emmanuel Nowak / Serge Timsit

    BMC Public Health, Vol 21, Iss 1, Pp 1-

    an ecological study based on data from the Brest stroke registry in France

    2021  Volume 10

    Abstract: Abstract Background Mapping the spatial distribution of disease occurrence is a strategy to identify contextual factors that could be useful for public health policies. The purpose of this ecological study was to examine to which extent the socioeconomic ...

    Abstract Abstract Background Mapping the spatial distribution of disease occurrence is a strategy to identify contextual factors that could be useful for public health policies. The purpose of this ecological study was to examine to which extent the socioeconomic deprivation and the urbanization level can explain gender difference of geographic distribution in stroke incidence in Pays de Brest, France between 2008 and 2013. Methods Stroke cases aged 60 years or more were extracted from the Brest stroke registry and combined at the census block level. Contextual socioeconomic, demographic, and geographic variables at the census block level come from the 2013 national census. We used spatial and non-spatial regression models to study the geographic correlation between socioeconomic deprivation, degree or urbanization and stroke incidence. We generated maps using spatial geographically weighted models, after longitude and latitude smoothing and adjustment for covariates. Results Stroke incidence was comparable in women and men (6.26 ± 3.5 vs 6.91 ± 3.3 per 1000 inhabitants-year, respectively). Results showed different patterns of the distribution of stroke risk and its association with deprivation or urbanisation across gender. For women, stroke incidence was spatially homogeneous over the entire study area, but was associated with deprivation level in urban census blocks: age adjusted risk ratio of high versus low deprivation = 1.24, [95%CI 1.04–1.46]. For men, three geographic clusters were identified. One located in the northern rural and deprived census blocks with a 9–14% increase in the risk of stroke. Two others clusters located in the south-eastern (mostly urban part) and south-western (suburban and rural part) with low deprivation level and associated with higher risk of stroke incidence between (3 and 8%) and (8.5 and 19%) respectively. There were no differences in profile of cardiovascular risk factors, stroke type and stroke severity between clusters, or when comparing clusters cases to the rest of the study ...
    Keywords Stroke ; Socioeconomic factors ; Urban rural ; Incidence ; geographically weighted regression (GWR) ; spatial variations ; Public aspects of medicine ; RA1-1270
    Subject code 910
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A Collet–Sicard syndrome due to internal carotid artery dissection associated with cerebral amyloid angiopathy–related inflammation

    Vanessa Saliou / Douraied Ben Salem / Julien Ognard / Dewi Guellec / Pascale Marcorelles / François Rouhart / Fabien Zagnoli / Serge Timsit

    SAGE Open Medical Case Reports, Vol

    2018  Volume 6

    Abstract: Background: Cerebral amyloid angiopathy–related inflammation is a rare condition with approximately 100 reported cases. Its clinical manifestations are varied. We report here a novel presentation of this disease. Case presentation: A 61-year-old ... ...

    Abstract Background: Cerebral amyloid angiopathy–related inflammation is a rare condition with approximately 100 reported cases. Its clinical manifestations are varied. We report here a novel presentation of this disease. Case presentation: A 61-year-old Caucasian man presented with rapidly progressive paralysis of the IX, X, XI and XII right cranial nerves associated with right central facial nerve palsy. Brain computed tomography angiography and cerebral catheter angiography found a focal fusiform enlargement of the distal cervical portion of the right internal carotid artery, related to a pseudo-aneurysm suggesting an evolution of a dissection and intra-cranial vessel dysplasia. Brain magnetic resonance imaging showed multiple asymmetrical subcortical regions of hyperintensity on T2 fluid-attenuated inversion recovery sequences. Punctiform cortical hyposignals on T2-weighted gradient echo magnetic resonance imaging sequences were mostly congruent with the white matter hyperintensities. There was a decreased cerebral perfusion at the frontal hyperintense fluid-attenuated inversion recovery region. Spectrometry identified a lactate–lipid peak. A brain biopsy showed intravascular amyloid deposits. Corticosteroid therapy was initiated, leading to a dramatic improvement of both clinical condition and magnetic resonance imaging brain lesions. Conclusion: This case report suggests that extra-cranial vasculitis and dysplasia can exceptionally be found in patients satisfying cerebral amyloid angiopathy–related inflammation criteria.
    Keywords Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Delayed treatment with systemic (S)-roscovitine provides neuroprotection and inhibits in vivo CDK5 activity increase in animal stroke models.

    Bénédicte Menn / Stéphane Bach / Teri L Blevins / Mark Campbell / Laurent Meijer / Serge Timsit

    PLoS ONE, Vol 5, Iss 8, p e

    2010  Volume 12117

    Abstract: Although quite challenging, neuroprotective therapies in ischemic stroke remain an interesting strategy to counter mechanisms of ischemic injury and reduce brain tissue damage. Among potential neuroprotective drug, cyclin-dependent kinases (CDK) ... ...

    Abstract Although quite challenging, neuroprotective therapies in ischemic stroke remain an interesting strategy to counter mechanisms of ischemic injury and reduce brain tissue damage. Among potential neuroprotective drug, cyclin-dependent kinases (CDK) inhibitors represent interesting therapeutic candidates. Increasing evidence indisputably links cell cycle CDKs and CDK5 to the pathogenesis of stroke. Although recent studies have demonstrated promising neuroprotective efficacies of pharmacological CDK inhibitors in related animal models, none of them were however clinically relevant to human treatment.In the present study, we report that systemic delivery of (S)-roscovitine, a well known inhibitor of mitotic CDKs and CDK5, was neuroprotective in a dose-dependent manner in two models of focal ischemia, as recommended by STAIR guidelines. We show that (S)-roscovitine was able to cross the blood brain barrier. (S)-roscovitine significant in vivo positive effect remained when the compound was systemically administered 2 hrs after the insult. Moreover, we validate one of (S)-roscovitine in vivo target after ischemia. Cerebral increase of CDK5/p25 activity was observed 3 hrs after the insult and prevented by systemic (S)-roscovitine administration. Our results show therefore that roscovitine protects in vivo neurons possibly through CDK5 dependent mechanisms.Altogether, our data bring new evidences for the further development of pharmacological CDK inhibitors in stroke therapy.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2010-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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