Neuroprotection for Ischemic Stroke: Moving Past Shortcomings and Identifying Promising Directions

• Main Authors: Jason D. Huber, Charles L. Rosen, Aric F. Logsdon, Alisa S. Elliott, Noelle Lucke-Wold, Ryan C. Turner, Brandon Lucke-Wold
• Format: Article
• Language: English
• Published: MDPI AG 2013-01-01
• Series: International Journal of Molecular Sciences
• Subjects: ischemic stroke; comorbidity; aging; macrophage polarization
• Online Access: http://www.mdpi.com/1422-0067/14/1/1890

The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with preliminary success of ongoing clinical trials for anti-inflammatory compounds such as minocycline. We review the role of inflammation in stroke and in particular, the role of inflammatory cell recruitment and macrophage phenotype in the inflammatory process. Emerging evidence indicates an increasing role of neuro-immune crosstalk, which has led to increased interest in identification of peripheral biomarkers indicative of neural injury. It is our hope that identification and investigation of factors influencing stroke pathophysiology may lead to improved therapeutics.