Current Research and Scholarly Interests
Our laboratory is interested in elucidating the pathophysiology of acute cerebral ischemia and in developing neuroprotective treatments, as well as methods to restore neurologic function after stroke. Using rodent wild type, knock out and transgenic models of focal and global ischemia, we are investigating the physiologic processes leading from decreased blood flow after arterial occlusion to irreversible brain injury. A major focus of our work concerns the role of oxidative stress, inflammation and gene expression on necrotic and apoptotic mechnisms of ischemic cell death. Alterations in cerebral blood flow, neuronal metabolic activity, electrophysiology, and gene/protein expression are examined in relation to neurologic behavior. We are also studying the brain microenvironment during recovery after stroke and the effects of stem cell transplantation and enhanced neurogenesis in promoting recovery of function.
We have been successful in attenuating ischemic cerebral damage by inducing mild brain hypothermia (30-33 degrees C) or overexpression of various genes (glucose transporter, bcl-2, hsp70, calbindin, catalase, glutathione peroxidase, SOD) either before or after stroke. Transplantation of human neural stem cells after experimental stroke results in survival, targeted migration and differentiation into appropriate neuronal and glial cell types, while anti-inflammatory treatment enhances native neurogenesis and gliagenesis following stroke. Additionally, optogenetic stimulation restores motor-sensory behavior after stroke and we are exploring the underlying circuit plasticity and molecular changes reposible for restoring neurologic function.
Methodologies utilized in the laboratory include microsurgery, light and confocal microscopy, stereology, molecular biology techniques, FACS, magnetic resonance imaging, electrophysiology, cerebral blood flow measurements, gene transfer therapy, optogenetics and rodent behavioral analysis.
Our clinical research efforts focus on novel approaches for treating intracranial aneurysms, intracranial and spinal vascular malformations, occlusive cerebrovascular disease such as Moyamoya disease and stroke. These include advances in microsurgery, interventional neuroradiology, stereotactic radiosurgery, 3D imaging, surgical navigation, revascularization techniques, the use of mild brain hypothermia and other clinical neuroprotective agents, and neurotransplantation.