Prospects of Therapeutic Target and Directions for Ischemic Stroke

Abstract

Stroke is a serious, adverse neurological event and the third leading cause of death and disability worldwide. Most strokes are caused by a block in cerebral blood flow, resulting in neurological deficits through the death of brain tissue. Recombinant tissue plasminogen activator (rt-PA) is currently the only immediate treatment medication for stroke. The goal of rt-PA administration is to reduce the thrombus and/or embolism via thrombolysis; however, the administration of rt-PA must occur within a very short therapeutic timeframe (3 h to 6 h) after symptom onset. Components of the pathological mechanisms involved in ischemic stroke can be used as potential biomarkers in current treatment. However, none are currently under investigation in clinical trials; thus, further studies investigating biomarkers are needed. After ischemic stroke, microglial cells can be activated and release inflammatory cytokines. These cytokines lead to severe neurotoxicity via the overactivation of microglia in prolonged and lasting insults such as stroke. Thus, the balanced regulation of microglial activation may be necessary for therapy. Stem cell therapy is a promising clinical treatment strategy for ischemic stroke. Stem cells can increase the functional recovery of damaged tissue after post-ischemic stroke through various mechanisms including the secretion of neurotrophic factors, immunomodulation, the stimulation of endogenous neurogenesis, and neovascularization. To investigate the use of stem cell therapy for neurological diseases in preclinical studies, however, it is important to develop imaging technologies that are able to evaluate disease progression and to “chase” (i.e., track or monitor) transplanted stem cells in recipients. Imaging technology development is rapidly advancing, and more sensitive techniques, such as the invasive and non-invasive multimodal techniques, are under development. Here, we summarize the potential risk factors and biomarker treatment strategies, stem cell-based therapy and emerging multimodal imaging techniques in the context of stroke. This current review provides a conceptual framework for considering the therapeutic targets and directions for the treatment of brain dysfunctions, with a particular focus on ischemic stroke.

Involvement of Ceramide Metabolism in Cerebral Ischemia

“…Mechanical thrombectomy and thrombolysis are the reperfusion strategies, which are based on the restoration of the CBF. Neurorepair involves the restoration of brain function by regenerating the damaged cerebral tissue or establishing alternative neural pathways or synapses ( Kim J. H. et al, 2021 ; Romaus-Sanjurjo et al, 2021 ). Neuroprotection has been focused on reducing cell death after an ischemic event intervening in the ischemic cascade mechanisms such as inflammation, oxidative stress, endothelial damage, or excitotoxicity ( Chamorro et al, 2016 ).…”

Therapeutic effect of α7 nicotinic receptor activation after ischemic stroke in rats

“…Although neuroprotective stroke therapies have shown to be useful in preclinical cerebral ischemia, few of them have been successfully applied in clinical practice. 18 Hence, the development of novel imaging strategies based on targeting immune biomarkers with therapeutic and prognostic value is paramount in the treatment of stroke. Because of this, we have used advanced MRI and PET techniques to evaluate the therapeutic properties of α7 nAChRs on brain damage outcome, neuroinflammatory reaction, protease activation and blood vascular integrity during acute and subacute preclinical ischemic stroke.…”

Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke

“…Stem cell therapy following ischemic insults has proved to be a novel and promising therapeutic strategy in recent years. It promotes CNS plasticity and regeneration, angiogenesis, and immunomodulation [ 182 ]. The efficacy and safety of cell-based therapy have been confirmed in animal models.…”