ReviewThe transcriptome of cerebral ischemia

The molecular causality and response to stroke is complex. Yet, much of the literature examining the molecular response to stroke has focused on targeted pathways that have been well-characterized. Consequently, our understanding of stroke pathophysiology has made little progress by way of clinical therapeutics since tissue plasminogen activator was approved for treatment nearly a decade ago. The lack of clinical translation is in part due to neuron-focused studies, preclinical models of cerebral ischemia and the paradoxical nature of neuro-inflammation. With the evolution of the Stroke Therapy Academic Industry Roundtable criteria streamlining research efforts and broad availability of genomic technologies, the ability to decipher the molecular fingerprint of ischemic stroke is on the horizon. This review highlights preclinical microarray findings of the ischemic brain, discusses the transcriptome of cerebral preconditioning and emphasizes the importance of further characterizing the role of the neurovascular unit and peripheral white blood cells in mediating stroke damage and repair within the penumbra.

► Preconditioning and aging alter the genomic response to ischemia. ► Examining genomic response to ischemia within an aged neurovascular unit is complex. ► The peripheral white blood cells may play an important response to stroke recovery. ► Microarray studies may elucidate novel pathways related to ischemic damage. ► STAIR Criteria should be followed when designing preclinical studies of stroke.