Small Synthetic Hyaluronan Disaccharides Afford Neuroprotection in Brain Ischemia-Related models
Bases Anatomicas y Hemodinamicas del complejo de la arteria comunicante anterior.
Autores: J. Egea - E. Parada - V. Gomez-Rangel - I. Buendia - P. Negredo - E. Montell - R. Ruhí - J. Vergés - J.M. Roda - A.G. Garcia - M.G. Lopez
Abstract: —High molecular weight (HMW) glycosaminoglycanes of the extracellular matrix have been implicated in tissue repair.
Stroke is the third leading cause of death, behind cardiovascular diseases and cancer, and is a leading cause of serious, long-term disability. Although treatments for ischemic stroke have been rigorously investigated for two decades, up to now there is only one approved pharmacological treatment, the intravenous thrombolytic recombinant tissue plasminogen activator (rt-PA) (Jahan and Vinuela,2009). Despite the fact that thrombolytic rt-PA hasdemonstrated efficacy in treating patients withthrombotic stroke, the short time window, the risk ofhemorrhage and the requirement for computedtomography scan before the initiation of treatmentreduces the number of patients (around 4%) actuallyreceiving the drug; consequently, other approaches totreat stroke are urgently needed.
NF2 Genetic Alterations in Sporadic Vestibular Schwannomas: Clinical Implications
NF2 gene alterations may have a clinical impact in non-NF2 vestibular schwannomas
Autores: Luis Lassaletta - Miguel Torres-Martın - Carolina Pen˜a-Granero - Jose Maria Roda - Santiago Santa-Cruz-Ruiz - Javier S. Castresana - Javier Gavilan - Juan A. Rey
Abstract:It has been suggested that NF2 mutations might correlate with clinical expression of VS in NF2 patients. The aim of this study was to analyze the impact of genetic alterationsin theNF2gene on epidemiologic, clinical, and radiologicfeatures of patients with sporadic VS. The association betweencigarette consumption and the molecular genetic findings wasalso studied.
Novel multitarget ligand ITH33/IQM9.21 provides neuroprotection in in vitro and in vivo models related to brain ischemia
ITH33/IQM9.21 is a novel compound belonging to a family of glutamic acid derivatives...
Autores: Lorrio S, Gómez-Rangel V, Negredo P, Egea J, Leon R, Romero A, Dal-Cim T, Villarroya M, Rodriguez-Franco MI, Conde S, Arce MP, Roda JM, García AG, López MG.
Abstract: ITH33/IQM9.21 is a novel compound belonging to a family of glutamic acid derivatives, synthesized under the hypothesis implying that multitarget ligands may provide more efficient neuroprotection than single-targeted compounds.
In rat hippocampal slices, oxygen plus glucose deprivation followed by re-oxygenation (OGD/Reox) elicited 42% cell death. At 1 μM, ITH33/IQM9.21 mitigated this damage by 26% and by 55% at 3 μM. OGD/Reox also elicited mitochondrial depolarization, overproduction of reactive oxygen species (ROS), enhanced expression of nitric oxide synthase (iNOS) and reduction of GSH levels. These changes were almost fully prevented when 3 μM ITH33/IQM9.21 was present during slice treatment with OGD/Reox. In isolated hippocampal neurons, ITH33/IQM9.21 reduced [Ca(2+)](c) transients induced by a high K(+) depolarizing solution or glutamate. In a photothrombotic model of stroke in mice, intraperitoneal injection of ITH33/IQM9.21 at 1.25 mg/kg, 2.5 mg/kg or 5 mg/kg given before and during 2 days after stroke induction, reduced infarct volume by over 45%. Furthermore, when the compound was administered 1 h post-stroke, a similar effect was observed. In conclusion, these in vitro and in vivo results suggest that ITH33/IQM9.21 exhibits neuroprotective effects to protect the vulnerable neurons at the ischemic penumbra by an effective and multifaceted mechanism, mediated by reduction of Ca(2+) overload, providing mitochondrial protection and antioxidant actions.
Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid, Spain.