Rôle des récepteurs NMDA endothéliaux dans un modèle murin de sclérose en plaques

Macrez, Richard; Vivien, Denis; Docagne, Fabián

doi:10.1051/medsci/20163212008

Cited by 2 publications

(1 citation statement)

References 15 publications

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“…Association of worsening with the presence of markers of inflammation means that the inflammatory environment hinders reperfusion, or that in itself conditions the worse evolution that these patients present. It is thus interesting to note that tPA was also reported to promote transmigration of inflammatory cells across the blood-brain barrier, an effect dependent of NMDA receptors expressed on endothelial cells [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Worse Outcome in Stroke Patients Treated with rt-PA Without Early Reperfusion: Associated Factors

Iglesias‐Rey

Rodríguez‐Yáñez

Rodríguez‐Castro

et al. 2017

Transl. Stroke Res.

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Based on preclinical studies suggesting that recombinant tissue plasminogen activator (rt-PA) may promote ischemic brain injuries, we investigated in patients the possible risk of worse clinical outcome after rt-PA treatment as a result of its inability to resolve cerebral ischemia. Here, we designed a cohort study using a retrospective analysis of patients who received treatment with intravenous (4.5-h window) or intraarterial rt-PA, without or with thrombectomy. Controls were consecutive patients who did not receive recanalization treatment, who met all inclusion criteria. As a marker of reperfusion, we defined the variable of early neurological improvement as the difference between the score of the National Institute of Health Stroke Scale (NIHSS) (at admission and 24 h). The main variable was worsening of the patient’s functional situation in the first 3 months. To compare quantitative variables, we used Student’s t test or the Mann-Whitney test. To estimate the odds ratios of each independent variable in the patient’s worsening in the first 3 months, we used a logistic regression model. We included 1154 patients; 577 received rt-PA, and 577 served as controls. In the group of patients treated with rt-PA, 39.4% who did not present clinical reperfusion data developed worsening within 3 months after stroke compared with 3.5% of patients with reperfusion (P < 0.0001). These differences were not significant in the control group. In summary, administration of rt-PA intravenously or intraarterially without reperfusion within the first 24 h may be associated with a higher risk of functional deterioration in the first 3 months.

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Section: Discussionmentioning

confidence: 99%

Worse Outcome in Stroke Patients Treated with rt-PA Without Early Reperfusion: Associated Factors

Iglesias‐Rey

Rodríguez‐Yáñez

Rodríguez‐Castro

et al. 2017

Transl. Stroke Res.

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Calming Down Mast Cells with Ketotifen: A Potential Strategy for Multiple Sclerosis Therapy?

et al. 2020

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Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by extensive inflammation, demyelination, axonal loss and gliosis. Evidence indicates that mast cells contribute to immunopathogenesis of both MS and experimental autoimmune encephalomyelitis (EAE), which is the most employed animal model to study this disease. Considering the inflammatory potential of mast cells, their presence at the CNS and their stabilization by certain drugs, we investigated the effect of ketotifen fumarate (Ket) on EAE development. EAE was induced in C57BL/6 mice by immunization with MOG 35-55 and the animals were injected daily with Ket from the seventh to the 17th day after disease induction. This early intervention with Ket significantly reduced disease prevalence and severity. The protective effect was concomitant with less NLRP3 inflammasome activation, rebalanced oxidative stress and also reduced T cell infiltration at the CNS. Even though Ket administration did not alter mast cell percentage at the CNS, it decreased the local CPA3 and CMA1 mRNA expression that are enzymes typically produced by these cells. Evaluation of the CNS-barrier permeability indicated that Ket clearly restored the permeability levels of this barrier. Ket also triggered an evident lymphadenomegaly due to accumulation of T cells that produced higher levels of encephalitogenic cytokines in response to in vitro stimulation with MOG. Altogether these findings reinforce the concept that mast cells are particularly relevant in MS immunopathogenesis and that Ket, a known stabilizer of their activity, has the potential to be used in MS control.

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Rôle des récepteurs NMDA endothéliaux dans un modèle murin de sclérose en plaques

Cited by 2 publications

References 15 publications

Worse Outcome in Stroke Patients Treated with rt-PA Without Early Reperfusion: Associated Factors

Worse Outcome in Stroke Patients Treated with rt-PA Without Early Reperfusion: Associated Factors

Calming Down Mast Cells with Ketotifen: A Potential Strategy for Multiple Sclerosis Therapy?

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