Targeted Therapies for CNS Ischemia

Between advances in perfusion-based neuroimaging and the expanded use of thrombolytics and mechanical thrombectomy, the past decade has been witness to a fundamental shift in the way we diagnose and treat ischemic brain injury. While several agents are currently in phase III trials, there remain no approved neuroprotective agents for use in either acute ischemic stroke (AIS) or cardiac arrest.

Acute brain ischemia induces a cascade of cell-autonomous and non-autonomous responses, which remains a fundamental challenge to developing such interventions.  In addition to triggering neuronal necrosis and regulated cell death, ischemia-induced neuroinflammation contributes to neuron loss and impedes functional recovery. In addition, the shedding of damage-associated molecules from the post-ischemic CNS exacerbates neurovascular reperfusion injury by amplifying peripheral immune activation.

Areas of active investigation within our group include:

• Mapping ischemia signaling networks using transcriptional profiling and localization proteomics to identify novel drug targets
• Uncovering the effects of ‘Lung-Brain-Coupling’ on the neurovascular response to ischemia-reperfusion injury
• Developing 3rd generation tetracyclines as rescue therapies in cerebrovascular conditions