A5015421764- Protease and Inhibitor Mechanisms
- Acute Ischemic Stroke Management
- S100 Proteins and Annexins
- Neuroinflammation and Neurodegeneration Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Neuroscience and Neuropharmacology Research
- Traumatic Brain Injury and Neurovascular Disturbances
- TGF-β signaling in diseases
- Calpain Protease Function and Regulation
- Neurological Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Cerebrovascular and Carotid Artery Diseases
- Neurological Disorders and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Barrier Structure and Function Studies
- Cell Adhesion Molecules Research
- Neonatal and fetal brain pathology
- Endoplasmic Reticulum Stress and Disease
- Cerebrovascular and genetic disorders
- Signaling Pathways in Disease
- Anesthesia and Neurotoxicity Research
- Cell death mechanisms and regulation
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Cannabis and Cannabinoid Research
- Intracerebral and Subarachnoid Hemorrhage Research
Normandie Université
2016-2024
Physiopathologie et imagerie des troubles neurologiques
2017-2024
Inserm
2015-2024
Université de Caen Normandie
2015-2024
Cyceron
2015-2024
Établissement Français du Sang
2021-2022
Serine Proteases and Pathophysiology of the neurovascular Unit
2007-2017
University of Pennsylvania
2017
Centre Hospitalier Universitaire de Caen Normandie
2010-2017
KU Leuven
2014
Activated microglia play a central role in the inflammatory and excitotoxic component of various acute chronic neurological disorders. However, mechanisms leading to their activation latter context are poorly understood, particularly involvement N-methyl-D-aspartate receptors (NMDARs), which critical for excitotoxicity neurons. We hypothesized that express functional NMDARs would trigger neuronal cell death brain by modulating inflammation.We demonstrate murine human nervous system these...
Acute brain injuries have been identified as a risk factor for developing Alzheimer's disease (AD). Because glutamate plays pivotal role in these pathologies, we studied the influence of receptor activation on amyloid-β (Aβ) production primary cultures cortical neurons. We found that sublethal NMDA increased and secretion Aβ. This effect was preceded by an expression neuronal Kunitz protease inhibitory domain (KPI) containing precursor protein (KPI-APP) followed shift from α-secretase to...
Platelet cross-linking during arterial thrombosis involves von Willebrand Factor (VWF) multimers. Therefore, proteolysis of VWF appears promising to disaggregate platelet-rich thrombi and restore vessel patency in acute thrombotic disorders such as ischemic stroke, coronary syndrome, or limb ischemia. N-Acetylcysteine (NAC, a clinically approved mucolytic drug) can reduce intrachain disulfide bonds large polymeric proteins. In the present study, we postulated that NAC might cleave multimers...
The glial cell line-derived neurotrophic factor (GDNF) is first characterized for its trophic activity on dopaminergic neurons. Recent data suggested that GDNF could modulate the neuronal death induced by ischemia. purpose of this study was to characterize influence cultured cortical neurons subjected two paradigms injury (necrosis and apoptosis) have been identified during cerebral ischemia determine molecular mechanisms involved. First, we demonstrated both astrocytes express mRNA protein...
In the brain, expression of pleiotropic cytokine interleukin-6 (IL-6) is enhanced in various chronic or acute central nervous system disorders. However, significance IL-6 production such neuropathologic states remains controversial. The present study investigated role after cerebral ischemia. First, authors showed that focal ischemia rats early up-regulated mRNA, without affecting transcription its receptors (IL-6Ralpha and gp130). Similarly, striatal injection N-methyl-D-aspartate (NMDA)...
Background— Accumulating evidence demonstrates a critical involvement of tissue-type plasminogen activator (tPA) in pathological and physiological brain conditions. Determining whether how vascular tPA can cross the blood-brain barrier (BBB) to enter is thus important, not only during stroke but also Methods Results— In present work, we provide vivo that intravenous injection increases NMDA-induced striatal lesion absence BBB leakage. Accordingly, show crosses both after excitotoxic control...
Tissue-type plasminogen activator (tPA) has been involved in both physiological and pathological glutamatergic-dependent processes, such as synaptic plasticity, seizure, trauma, stroke. In a previous study, we have shown that the proteolytic activity of tPA enhances N-methyl-d-aspartate (NMDA) receptor-mediated signaling neurons (Nicole, O., Docagne, F., Ali, C., Margaill, I., Carmeliet, P., MacKenzie, E. T., Vivien, D., Buisson, A. (2001) Nat. Med. 7, 59–64). Here, show forms direct complex...
Various studies describe increased concentrations of transforming growth factor-β (TGF-β) in brain tissue after acute injury. However, the role endogenously produced TGF-β damage to CNS remains be clearly established. Here, authors examine influence an episode cerebral ischemia by injecting a soluble type II receptor fused with Fc region human immunoglobulin (TβRIIs-Fc). First, this molecular construct was characterized as selective antagonist TGF-β. Then, tested its ability reverse effect 1...
The anaphylatoxin C3a is a potent inflammatory polypeptide released at sites of complement activation. To test whether might alter neuronal outcome following an ischemic insult, we determined the effects purified human on murine primary cortical cell cultures exposed to apoptotic or excitotoxic paradigms. prevented neither serum deprivation-induced death, nor AMPA/kainate-mediated excitotoxicity. However, in mixed neurons and astrocytes, dose-dependently protected against NMDA toxicity (47%...
Background and Purpose— Despite uncontroversial benefit from its thrombolytic activity, the documented neurotoxic effect of tissue plasminogen activator (tPA) raises an important issue: current emergency stroke treatment might not be optimum if exogenous tPA can enter brain thus add to deleterious effects endogenous within cerebral parenchyma. Here, we aimed at determining whether vascular crosses blood–brain barrier (BBB) during ischemia, so, by which mechanism. Methods— First, BBB...
Tissue plasminogen activator (tPA) is the only available treatment for acute stroke. In addition to its vascular fibrinolytic action, tPA exerts various effects within brain, ranging from synaptic plasticity control of cell fate. To date, influence in ischemic brain has been investigated on neuronal, microglial, and endothelial We addressed mechanism action oligodendrocyte (OL) survival extent white matter lesions also impact aging these processes. observed that, parallel reduced levels OLs,...
Current thrombolytic therapy for acute ischemic stroke with tissue-type plasminogen activator (tPA) has clear global benefits. Nevertheless, evidences argue that in addition to its prohemorrhagic effect, tPA might enhance excitotoxic necrosis. In the brain parenchyma, tPA, by binding and then cleaving amino-terminal domain (ATD) of NR1 subunit N-methyl-d-aspartate (NMDA) glutamate receptors, increases calcium influx toxic levels. We show here binds ATD a two-sites system ( K D =24 nmol/L)....
Tissue-type plasminogen activator (tPA) is the only drug approved for acute treatment of ischemic stroke but with two faces in disease: beneficial fibrinolysis vasculature and damaging effects on neurovascular unit brain parenchyma. To improve this profile, we developed a novel strategy, relying antibodies targeting proneurotoxic tPA.After production characterization (αATD-NR1) that specifically prevent interaction tPA ATD-NR1 N-methyl-d-aspartate receptors, have evaluated their efficacy...