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Smad proteins play a key role in the intracellular signalling of transforming growth factor beta (TGF beta), which elicits a large variety of cellular responses. Upon TGF beta receptor activation, Smad2 and Smad3 become phosphorylated and form heteromeric complexes with Smad4. These complexes translocate to the nucleus where they control expression of(More)
Tissue-plasminogen activator (t-PA) is now available for the treatment of thrombo-embolic stroke but adverse effects have been reported in some patients, particularly hemorrhaging. In contrast, the results of animal studies have indicated that t-PA could increase neuronal damage after focal cerebral ischemia. Here we report for the first time that t-PA(More)
Cyclic AMP (cAMP) is produced by activation of Gs protein-coupled receptors and regulates many physiological processes through activation of protein kinase A (PKA). However, a large body of evidence indicates that cAMP also regulates specific cellular functions through PKA-independent pathways. Here, we show that a small GTPase of the Rho family, Rac, is(More)
Erythropoietin (Epo), the major hormone controlling the hypoxia-induced increase in the number of erythrocytes, has also a functional role in the brain. However, few data exist as to the cellular source of brain-derived Epo as well as to the molecular mechanisms that control Epo expression in the central nervous system. Using patch-clamp and RT-PCR methods,(More)
Thrombolysis with tissue-type plasminogen activator (tPA) is used for the treatment of patients with acute ischemic stroke. However, a growing body of evidence indicates that, besides the unquestionable benefit from its thrombolytic activity, tPA also has a deleterious effect on the ischemic brain including cytotoxicity and increased permeability of the(More)
The tissue type plasminogen activator (t-PA) is a serine protease that is involved in neuronal plasticity and cell death induced by excitotoxins and ischemia in the brain. t-PA activity in the central nervous system is regulated through the activation of serine protease inhibitors (serpins) such as the plasminogen activator inhibitor (PAI-1), the protease(More)
Transforming growth factor-beta (TGF-beta) has been characterized as an injury-related factor, based on the observation that it is strongly up-regulated in many acute or chronic central nervous system disorders. TGF-beta is generally thought to be neuroprotective and several mechanisms have been proposed to explain this beneficial action. For instance,(More)
OBJECTIVE Activated microglia play a central role in the inflammatory and excitotoxic component of various acute and chronic neurological disorders. However, the mechanisms leading to their activation in the latter context are poorly understood, particularly the involvement of N-methyl-D-aspartate receptors (NMDARs), which are critical for excitotoxicity in(More)
Stroke is the second most common cause of death worldwide and a major cause of acquired disability in adults. Despite tremendous progress in understanding the pathophysiology of stroke, translation of this knowledge into effective therapies has largely failed, with the exception of thrombolysis, which only benefits a small proportion of patients. Systemic(More)
Various studies describe increased concentrations of transforming growth factor-beta (TGF-beta) in brain tissue after acute brain injury. However, the role of endogenously produced TGF-beta after brain damage to the CNS remains to be clearly established. Here, the authors examine the influence of TGF-beta produced after an episode of cerebral ischemia by(More)