Stroke is a leading cause of death and long-term disabilities. Despite decades of extensive efforts in search of brain injury mechanisms and therapeutic interventions, pharmacological treatment is limited to the use of thrombolytic agent tissue plasminogen activator, which has limited therapeutic time window and potential side effect of intracranial hemorrhage. Over the past few years, endovascular thrombectomy with stent-retriever devices combined with advanced imaging modalities has transformed the standard of stroke care, offering an opportunity to improve the outcome in selected patients as late as 24 h after the onset of stroke. This mini-review summarizes the advancement in the treatment of ischemic stroke, from thrombolysis to thrombectomy and remaining challenges in the field.
Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate a distinct family of ion channels, the acid-sensing ion channels (ASICs), has shed new light on the mechanism of acid signaling and acidosis-associated neuronal injury. Accumulating evidence has suggested that ASICs play important roles in physiological processes such as synaptic plasticity, learning/memory, fear conditioning, and retinal integrity, and in pathological conditions such as brain ischemia, multiple sclerosis, epileptic seizures, and malignant glioma. Thus, targeting these channels may lead to novel therapeutic interventions for neurological disorders. The goal of this review is to provide an update on recent advances in our understanding of the functions of ASICs in the CNS.
1 March 2017 in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease