Stroke remains a leading cause of adult disability with treatments limited to thrombolytic therapies that are severely limited by a narrow therapeutic window. The potential of hundreds of other therapeutic agents cannot be evaluated due to their poor ability to cross the blood-brain barrier. Recently, biopolymer hydrogels have shown promise at overcoming these obstacles via the delivering of therapeutic molecules (pharmacological, mRNA, stem cells, etc.
View Article and Find Full Text PDFStroke-induced cognitive impairments remain of significant concern, with very few treatment options available. The involvement of glycosaminoglycans in neuroregenerative processes is becoming better understood and recent advancements in technology have allowed for cost-effective synthesis of novel glycomimetics. The current study evaluated the therapeutic potential of two novel glycomimetics, compound A and G, when administered systemically five-days post-photothrombotic stroke to the PFC.
View Article and Find Full Text PDFCa/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα) is a key neuronal signaling protein and an emerging drug target. The central hub domain regulates the activity of CaMKIIα by organizing the holoenzyme complex into functional oligomers, yet pharmacological modulation of the hub domain has never been demonstrated. Here, using a combination of photoaffinity labeling and chemical proteomics, we show that compounds related to the natural substance γ-hydroxybutyrate (GHB) bind selectively to CaMKIIα.
View Article and Find Full Text PDFIschemic stroke remains a leading cause of disability worldwide, with limited treatment options available. This study investigates GABA receptors as novel pharmacological targets for stroke recovery. The expression of 1 and 2 mRNA in mice were determined in peri-infarct tissue following photothrombotic motor cortex stroke.
View Article and Find Full Text PDFStroke-induced cognitive impairments are of significant concern, however mechanisms that underpin these impairments remain poorly understood and researched. To further characterise cognitive impairments in our frontal cortex stroke model, and to align our assessments with what is used clinically, we tested young C57BL/6J mice trained in operant touchscreen chambers to complete the trial-unique nonmatched-to-location (TUNL) task. Based on baseline performance, animals were given either stroke (n = 12) or sham (n = 12) surgery using a photothrombosis model, bilaterally targeting the frontal cortex.
View Article and Find Full Text PDFStroke remains the leading cause of long-term disability with limited options available to aid in recovery. Significant effort has been made to try and minimize neuronal damage following stroke with use of neuroprotective agents, however, these treatments have yet to show clinical efficacy. Regenerative interventions have since become of huge interest as they provide the potential to restore damaged neural tissue without being limited by a narrow therapeutic window.
View Article and Find Full Text PDFStroke remains a leading cause of disability worldwide. Recently, we have established an animal model of stroke that results in delayed impairment in spatial memory, allowing us to better investigate cognitive deficits. Young and aged brains show different recovery profiles after stroke; therefore, we assessed aged-related differences in poststroke cognition.
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