rfr102

Raymond F. Regan, MD

Contact Dr. Regan

900 Walnut Street
Philadelphia, PA 19107

(215) 955-6844
(215) 923-6225 fax

Research and Clinical Interests

Hemorrhagic Stroke

The aim of our research is to define the molecular mechanisms that contribute to the death of CNS cells after an intracerebral hemorrhage (ICH), a type of stroke that has a very high morbidity and mortality and, currently, very limited treatment options. For many years, injury after ICH was attributed to the mass effect of the hematoma, which presumably caused ischemia by compressing adjacent tissue, impeding blood flow. However, over the past decade, regional blood flow and oxygen extraction studies have often failed to demonstrate ischemia in this tissue, even after large hemorrhages associated with considerable morbidity and mortality. An alternate hypothesis, which is the current focus of our research, is that toxins released from the hematoma may contribute to injury to surrounding tissue. Our laboratory is particularly interested in the oxidative injury produced by hemoglobin, which is the most abundant protein in blood. After its release by lysed erythrocytes, the heme moieties of hemoglobin are broken down to iron, carbon monoxide, and biliverdin in a reaction catalyzed by the heme oxygenase enzymes. Neurons appear to be particularly vulnerable to hemoglobin, perhaps due to their very limited ability to sequester and detoxify iron.

We use both cell culture and in vivo models. Primary neuron and astrocyte cultures are used to test the effect of gene knockout or gene transfer on cell vulnerability to hemoglobin and other oxidants. They are also used for pharmacologic screening.In vivo, ICH is modeled by stereotactic injection of either autologous blood or collagenase into the mouse striatum; the latter produces a hemorrhage by disrupting local blood vessels. Methods in common use include immunoblotting, fluorescence imaging, and assays to detect protein oxidation, lipid oxidation, and cell viability.

Our ultimate goal is to develop novel therapies for ICH that minimize cell injury and neurologic deficits