Insights into Therapeutic Targets in Stroke

Abstract

A stroke is also called a cerebrovascular accident which damages the brain from interruption of blood supply. Vast research has been developed to date to develop accurate treatment and alternatives to only one FDA-approved therapy, t-PA. Also, recent techniques such as stem cells for regeneration and imaging techniques for early diagnosis of stroke have been employed. However, the research has gained limited success in achieving desired results. It’s because of the multifaceted pathophysiology of stroke and limitations of novel or existing therapies along with the inappropriate preclinical design and drug discovery of experiments. Nanotechnology applications in stroke research have shown promising effects in preclinical stages. They are advantageous due to their surface modification properties and to overcome the limitations of existing therapies. They are used for a theranostic purpose as a drug delivery carrier, contrast agent for imaging, gene delivery, coating agent, or targeting agent. However, this technique requires an in-depth understanding of the use and selection of carriers and their pharmacokinetics, toxicity, sensitivity, selectivity, capacity to be imaged with commercially available equipment, etc. Understanding the pathophysiology of stroke is very crucial for the selection of targets, choice of therapeutic agent, selection of nanoformulations, etc. as it involves multiple pathways. Moreover, a combination of drugs or selection of drugs targeting multiple targets is also important and has to take into consideration. More research is required to make wise use of these techniques to translate to the clinical trials and make them successful in stroke therapy. So, in this book chapter, we have covered the pathophysiology-based therapeutic approaches with a particular focus on ischemic penumbra. Molecules released and can be targeted in salvageable ischemic penumbra include apoptotic markers, free radicals, ion channels, glutaminergic signaling, activated protein C, GABA A receptors, antioxidant levels, reperfusion, etc.

Nanomaterials used as a contrast agent in the diagnosis of stroke include metal nanoparticles, quantum dots, polymeric nanoparticles, dendrimers, etc. with their characteristics and examples. Nanoparticles used as drug carriers in stroke therapy include carbon nanotubes, metal nanoparticles, polymeric nanoparticles, liposomes, quantum dots, dendrimers, graphene, black phosphorous, hydrogels, etc. Further, their limitations and approaches are discussed. Nanomaterials target receptors such as EPOR, TfR, CACR4, LDL, and lactoferrin receptor. Future perspectives in stroke therapy are also covered which have to be taken into consideration while selecting the diagnostic and therapeutic strategy for stroke.