Neuroscience
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Spreading depolarization (SD) is a slowly propagating wave of prolonged activation followed by a period of synaptic suppression. Some prior reports have shown potentiation of synaptic transmission after recovery from synaptic suppression and noted similarities with the phenomenon of long-term potentiation (LTP). Since SD is increasingly recognized as participating in diverse neurological disorders, it is of interest to determine whether SD indeed leads to a generalized and sustained long-term strengthening of synaptic connections. ⋯ Potentiation was saturated after a single SD and adenosine A1 receptor activation did not mask additional potentiation. Induction of LTP with theta-burst stimulation was not altered by prior induction of SD and molecular mediators known to block LTP induction did not block SD-induced potentiation. Together, these results indicate an intermediate duration potentiation that is distinct from hippocampal LTP and may have implications for circuit function for 1-2 h following SD.
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Gamma-aminobutyric acid and glycine (GABA/Gly) are predominantly inhibitory neurotransmitters in the mature central nervous system; however, they mediate membrane potential depolarization during development. These differences in actions depend on intracellular Cl- concentrations ([Cl-]i), which are primarily regulated by potassium chloride cotransporter 2 (KCC2). After nerve injury, KCC2 expression markedly decreases and GABA/Gly mediate depolarization. ⋯ These results suggest that nerve degeneration and regeneration proceed more rapidly in HT mice, resulting in milder motor dysfunction. Via similar microglial activation, nerve surgery may reduce KCC2 levels more rapidly in HT mice, followed by earlier increased [Cl-]i and longer-lasting GABA/Gly excitation. Taken together, reduced KCC2 may accelerate nerve regeneration via GABA/Gly excitation.
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Following a stroke, an inflammatory response occurs, characterized by an increased blood-brain barrier permeability, expression of endothelial trafficking molecules, and infiltration of immune cells. Adhesion molecules expressed on activated brain endothelial cells are potential biomarkers of intraparenchymal inflammation. ⋯ In this review, we highlight the most recent studies that used immuno-MRI in models of neurovascular disorders, including transient ischemic attack, ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage. We also discuss the potential of immuno-MRI in clinical practice and the necessary next steps for its implementation in patients.
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Stroke is responsible for 11% of all deaths worldwide, the majority of which are caused by ischemic strokes, thus making the need to urgently find safe and effective therapies. Today, these can be cured either by mechanical thrombectomy when the thrombus is accessible, or by intravenous injection of fibrinolytics. However, the latter present several limitations, such as potential severe side effects, few eligible patients and low rate of partial and full recovery. ⋯ Then, it will present the different nanoparticle types that have been recently developed to treat this pathology. It will also study the various targeting strategies used to bring nanoparticles to the stroke site, thereby limiting side effects and improving the therapeutic efficacy. Finally, this review will present the few clinical studies testing nanomedicine on stroke and discuss potential causes for their scarcity.
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Stroke is the most common cause of disability. Brain repair mechanisms are often insufficient to allow a full recovery. Stroke damage involve all brain cell type and extracellular matrix which represent the crucial "glio-neurovascular niche" useful for brain plasticity. ⋯ MSC, mononuclear cells (MNC), umbilical cord stem cells and NSC are the most investigated. Innovative approaches are implemented concerning combinatorial approaches with growth factors and biomaterials such as injectable hydrogels which could protect a cell graft and/or deliver drugs into the post-stroke cavity at chronic stages. Through main publications of the last two decades, we provide in this review concepts and suggestions to improve future translational researches and larger clinical trials of cell therapy in stroke.