Dr. E. Sander Connolly’s Cerebrovascular Laboratory employs experimental models to study the mechanisms of cerebral ischemia/reperfusion injury, with a focus on clinical translation.  The NIH is funding the effort to analyze a recently identified a component of the complement cascade that mediates post-ischemic cerebral injury, and we are currently to delineate the mechanisms of this injury, and to develop specific techniques of targeting complement and translating these findings to human neuroprotective trials.

Related basic science projects include an active collaboration with Dr. Carol Troy seeks to understand novel mechanisms of caspase-mediated post-ischemic neuronal cell death/survival.  In addition, recent laboratory studies are underway to study the role of the complement cascade, programmed cell death, and neurogenesis in spontaneous intracerebral hemorrhage, as well.

We have recently begun recruiting patients for an FDA-funded multicenter, phase II clinical trial aimed at assessing the safety of tiopronin in patients with aneurysmal subarachnoid hemorrhage(aSAH) and also to obtain preliminary data on the efficacy of tiopronin versus placebo in reducing serum and CSF 3AP levels in this stroke patient population. Collaborating principle investigators participating in this trial include Dr. Brian L. Hoh and Dr. J. Mocco from the Neurosurgery Department at the University of Florida, and also Dr. Louis J. Kim from the Neurosurgery Department at the University of Washington.

Other clinical research efforts include those concerning vascular re-activation of large and small cerebral vessels through the effects of subarachnoid hemorrhage and other trauma, and the auto-regulation of vessels in relation to arteriovenous malformations and other pathological vascular conditions.  In collaboration with Dr. Eric Heyer (Anesthesiology), the lab has also shown that possession of the ε4 allele of the ApoE gene (originally characterized in Alzheimer’s Diseases) is a risk factor for neurocognitive decline following carotid endarterectomy.  Researchers in the laboratory also play a pivotal role in the international effort to identify genes responsible for the formation of cerebral aneurysms.