Neuroprotective effect of masitinib in rats with postischemic stroke

Kocić, Ivan; Kowiański, Przemysław; Rusiecka, Izabela; Lietzau, Grażyna; Mansfield, Colin D.; Moussy, Alain; Hermine, Olivier; Dubreuil, Patrice

doi:10.1007/s00210-014-1061-6

Cited by 25 publications

(23 citation statements)

References 43 publications

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“…[13] Therefore, it has long been stressed that there is a connection between the severity of inflammation, the size of the area affected by ischemia and the degree of neurological deficit. [14] In this study, both the increased leukocyte count and the CRP on the first day of the disease were significantly associated with a more severe neurological status in the ultra-acute phase of the disease and with the functional status on the 30th day. Our results are consistent with previous reports and may be supportive of anti-inflammatory strategies in the treatment of stroke.…”

Section: Discussionsupporting

confidence: 47%

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

Lasek–Bal

Jędrzejowska–Szypułka

Student

et al. 2018

Preprint

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Acute cerebral ischemia triggers local and systemic immune response. The aims of this project was to assess the blood serum concentration of the markers of inflammation and markers of the blood brain barrier damage on the first day of ischemic stroke, and the mutual correlations between these marker levels. Methods Our prospective study included 138 patients with first-in-life stroke, who were analyzed according to: plasma concentration of the following markers on the first day of stroke: Il-2 and IL-6, S100B, TNF alfa, GRN, NSE, uPA, VEGF, BDNF, CRP, leucocyte and thrombocyte counts; their neurological status on the first day of stroke (NIHSS) and their functional status at 30 days following stroke (mRS). Result The study included 138 patients with mean age: 73.11 ± 11.48 [36-103]. Patients with a higher score on the NIHSS than those obtaining lower scores showed significantly higher concentrations of TNF-alpha, WBC, CRP, NSE, IL-6 and S100B. Patients with a higher score on the mRS than those obtaining lower scores showed significantly higher concentrations of WBC, CRP, GRN, IL-6, S100B. Factors with an independent influence on the neurological status on the first day of stroke were: sex, WBC, PLT, CRP, S100B and IL-6 levels. Atrial fibrillation, leukocyte count, CRP, NSA, uPA, interleukin 6 and S100B showed an independent impact on the functional status on the 30th day of stroke. Patients with symptomatic atherosclerosis of carotid/cerebral and/or coronary arteries, as compared to others, were older (p= 0.003) and had higher levels of CRP, Il-6, and S100B. In each case, the differences were statistically significant. Conclusions The concentration of Il-6 and S100B on the first day of stroke are significant for both the neurological status and the functional status in the acute period of the disease. Increased CRP and leukocyte count are associated with a worse prognosis regarding the course of acute stroke. The expression of pro-inflammatory agents and markers of blood-brain barrier damage in the acute phase of stroke is more prominent in patients with symptomatic atherosclerosis than in patients with no clinical features of atherosclerosis.

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Section: Discussionsupporting

confidence: 47%

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

Lasek–Bal

Jędrzejowska–Szypułka

Student

et al. 2018

Preprint

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“…The role of peripheral monocytes/macrophages remains controversial. There is no clear evidence that they can infiltrate the spinal cord and contribute to MN death [105] unless there is a disruption in the blood-brain barrier [106]. However, their damaging action on peripheral axons has been well recognized [107].…”

Section: Peripheral Immune Systemmentioning

confidence: 99%

Therapeutic Strategies Under Development Targeting Inflammatory Mechanisms in Amyotrophic Lateral Sclerosis

et al. 2017

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Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by the progressive loss of cortical, bulbar, and spinal motor neurons (MNs). The cardinal manifestation of ALS is a progressive paralysis which leads to death within a time span of 3 to 5 years after disease onset. Despite similar final output of neuronal death, the underlying pathogenic causes are various and no common cause of neuronal damage has been identified to date. Inflammation-mediated neuronal injury is increasingly recognized as a major factor that promotes disease progression and amplifies the MN death-inducing processes. The neuroimmune activation is not only a physiological reaction to cell-autonomous death but is an active component of nonautonomous cell death. Such injury-perpetuating phenomenon is now proved to be a common mechanism in many human disorders characterized by progressive neurodegeneration. Therefore, it represents an interesting therapeutic target. To date, no single cell population has been proved to play a major role. The existing evidence points to a complex cross talk between resident immune cells and nonresident cells, like monocytes and T lymphocytes, and to a dysregulation in cytokine profile and in phenotype commitment. After a summary of the most important mechanisms involved in the inflammatory reaction in ALS, this review will focus on novel therapeutic tools that rely on tackling inflammation to improve motor function and survival. Herein, completed, ongoing, or planned clinical trials, which aim to modify the rapidly fatal course of this disease, are discussed. Anti-inflammatory compounds that are currently undergoing preclinical study and novel suitable molecular targets are also mentioned.

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“…Accordingly, clinical trials have shown therapeutic effects of masitinib in cases of mastocytosis, a rare disease characterized by abnormal accumulation and activation of mast cells in various tissues and organs (28). Masitinib was also shown to beneficially modulate CNS function in multiple sclerosis (29), stroke (30), and Alzheimer' s disease (31). In addition, a recent phase III clinical trial with masitinib in ALS has shown promising therapeutic effects in a significant group of patients, slowing the deterioration of motor functions and reducing the decline in quality of life (32).…”

Section: Introductionmentioning

confidence: 99%

Evidence for mast cells contributing to neuromuscular pathology in an inherited model of ALS

Trías¹,

Ibarburu²,

Barreto-Núñez³

et al. 2017

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Neuroprotective effect of masitinib in rats with postischemic stroke

Cited by 25 publications

References 43 publications

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

Therapeutic Strategies Under Development Targeting Inflammatory Mechanisms in Amyotrophic Lateral Sclerosis

Evidence for mast cells contributing to neuromuscular pathology in an inherited model of ALS

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