Delivery of Neurotherapeutics Across the Blood Brain Barrier in Stroke

Abstract

Stroke is a devastating disease with few therapeutic options. Despite our growing understanding of the critical mechanistic events in post-stroke brain injury, the clinical translation of these findings has been less effective. A monumental hurdle to the field has been the inability of many systemically applied therapies to efficiently cross the blood brain barrier (BBB) and enter brain cells. Over the last two decades, however, significant technological achievements have overcome this obstacle to facilitate central nervous system (CNS) drug delivery. Noninvasive drug carriers, especially cell penetrating peptide (CPP) show great potential to deliver neurotherapeutics across the BBB for the treatment of ischemic brain injury. This review begins with a brief introduction to the BBB in relation to drug delivery and then provides an overview of the development of drug carriers for neurotherapeutics, with a focus on CPP-mediated transduction. We discuss recent advances and limitations in this field, as well as mechanisms underlying CPP-mediated brain targeting. We also summarize the application of CPPs in stroke research. Continuing modifications and improvements of CPPs are expected to enhance both their feasibility in clinical stroke management and their specificity towards particular cell types.

Ulinastatin May Significantly Improve Postoperative Cognitive Function of Elderly Patients Undergoing Spinal Surgery by Reducing the Translocation of Lipopolysaccharide and Systemic Inflammation

“…Organic inflammatory response can promote the generation of MMP-9. MMP-9 can resolve and destroy the basement membrane of BBB (Blood Brain Barrier), may change the cerebral vascular permeability and cause the BBB impairment ( Hu et al, 2012 ). In our study, the concentration of MMP-9 increased quickly at the end of operation and was higher in control group than in the ulinastatin group at 24 and 72 h postoperation.…”

“…Organic inflammatory response can promote the generation of MMP-9. MMP-9 can resolve and destroy the basement membrane of BBB (Blood Brain Barrier), may change the cerebral vascular permeability and cause the BBB impairment ( Hu et al, 2012 ). BBB permeability changes can promote a large number of circulatory system inflammatory mediators around the central nervous system, a direct attack on neuronal cells or indirect activation of microglial cells, resulting in a series of physiological and pathological processes, and eventually resulting in abnormalities in nerve cells, as well as clinical manifestations of postoperative short-term cognitive decline ( Bruno et al, 2009 ).…”

Breaking the Barrier in Stroke: What Should we Know? A Mini-Review

“…Next Dr. Jun Chen and his research team review the modern topic of neurotherapeutics across the BBB [37]. The therapeutic potential of cell penetrating peptide is explored and its function as an important mediator of transduction is discussed, drawing from a series of preclinical studies demonstrating that arresting the apoptotic pathway via genetic manipulationpromotes neuroprotection against stroke [38, 39, 40].…”

Targeted drug delivery to ischemic stroke via chlorotoxin-anchored, lexiscan-loaded nanoparticles

“…9,10 The BBB is a vital element in regulation of the constancy of the internal environment of the brain, but it also largely hinders the delivery of most therapeutic agents to the brain. 11,12 The BBB may be partially disrupted in later stages following stroke, as evident in 33% of ischemic human patients.…”