Philadelphia University + Thomas Jefferson University

Regan, Raymond F

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Raymond F. Regan, MD

Contact Dr. Regan

900 Walnut Street
JHN 4th floor
Philadelphia, PA 19107

(215) 955-6844
(215) 503-4358 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


Most Recent Peer-Reviewed Publications

  1. Astrocyte heme oxygenase-1 reduces mortality and improves outcome after collagenase-induced intracerebral hemorrhage
  2. Targeting the Nrf2-heme oxygenase-1 axis after intracerebral hemorrhage
  3. Haptoglobin increases the vulnerability of CD163-expressing neurons to hemoglobin
  4. Dysregulation of the haem-haemopexin axis is associated with severe malaria in a case-control study of Ugandan children
  5. Solid microparticles based on chitosan or methyl-β-cyclodextrin: A first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate
  6. Astrocyte Overexpression of Heme Oxygenase-1 Improves Outcome after Intracerebral Hemorrhage
  7. Curcumin-induced heme oxygenase-1 expression prevents H<inf>2</inf>O<inf>2</inf>-induced cell death in wild type and heme oxygenase-2 knockout adipose-derived mesenchymal stem cells
  8. Neuroprotective effect of heme oxygenase-2 knockout in the blood injection model of intracerebral hemorrhage
  9. Hemin uptake and release by neurons and glia
  10. Systemic hemin therapy attenuates blood-brain barrier disruption after intracerebral hemorrhage
  11. Delayed cutaneous wound closure in HO-2 deficient mice despite normal HO-1 expression
  12. A rapid fluorescent method to quantify neuronal loss after experimental intracerebral hemorrhage
  13. Effect of Iron Chelators on Methemoglobin and Thrombin Preconditioning
  14. Hemopexin decreases hemin accumulation and catabolism by neural cells
  15. Iron accumulation and neurotoxicity in cortical cultures treated with holotransferrin
  16. Increased striatal injury and behavioral deficits after intracerebral hemorrhage in hemopexin knockout mice: Laboratory investigation
  17. Apotransferrin protects cortical neurons from hemoglobin toxicity
  18. Iron regulatory protein-2 knockout increases perihematomal ferritin expression and cell viability after intracerebral hemorrhage
  19. Accelerated hemolysis and neurotoxicity in neuron-glia-blood clot co-cultures
  20. Heme oxygenase-2 deletion causes endothelial cell activation marked by oxidative stress, inflammation, and angiogenesis