Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

Molecular, Genetic Function During CerebralArtery Response to Ischemia, Low Flow andRadiation Link Clinical and Basic ResearchDr. Marc Mayberg leads a group ofclinician-scientists who are investigatingbasic pathophysiologic mechanismsunderlying stroke. The clinician-scientists in thisgroup all maintain clinical practices in thetreatment of patients with cerebrovasculardiseases and bring clinical expertise into laboratoryinvestigation and vice versa. Dr. Mayberg’sresearch program concernsthe response of cerebralarteries to various injuries,including ischemia, lowflow and radiation.Ljiljana Bengez, M.D.,Ph.D., and EdwinCunningham, M.D., use anin vitro model of theblood-brain barrier toinvestigate the respectiveroles of hypoxia,hypoglycemia, flow andsteroids in the modulationof the inflammatoryresponse by elements ofthe vessel wall andsubsequent alterations inthe blood-brain barrier.Young-Soo Kim, M.D.,uses the same model toinvestigate the role ofmatrix metalloproteaseactivation and thebreakdown of bloodbrainbarrier in the same settings. Both of theseresearch efforts are essential in understanding thepathophysiology of important clinical conditionssuch as hemorrhagic stroke, reperfusion injury,and ischemic pre-conditioning in the brain. Dr.Mayberg is directing a research program toinvestigate the response of cerebral arteries toMarc Mayberg, M.D.radiation. Using in vitro and in vivo models, hisresearch program will characterize gene activation,blood-brain barrier dynamics, and cellturnover in the blood vessel wall after exposureto ionizing radiation. John Perl, M.D., isinvestigating the application of new endovasculartechnologies to treatment of cerebrovasculardisorders. His research, in association with thatof Younghua Dong, M.D.,involves the developmentof mechanical thrombolysisand magnetically guidedcatheters to treat strokeand aneurysms in previouslyinaccessible parts ofthe cerebral circulation.Peter Rasmussen, M.D., isinvestigating disruption ofthe blood-brain barrierafter intracerebralhemorrhage in an animalmodel and the potentialutility of rapid minimallyinvasive hematomaevacuation using mechanicalthrombolysis. MichaelDeGeorgia, M.D., andDerk Krieger, M..D., areinvestigating the cellularmechanisms of hypothermicprotection againstcerebral ischemia and newapplications of intraarterialcooling devices in animal models ofintracerebral hemorrhage and stroke. Observationsfrom these investigations will be directlyapplicable to concurrent Intensive Care Unitprotocols using hypothermia in Neuro-ICUpatients.THE MAYBERGLABORATORYSTROKEINTERVENTION/HYPOTHERMIARESEARCHCLINICIAN INVESTIGATORSMichael DeGeorgia, M.D. 1Derk Krieger, M.D. 1John Perl, M.D. 2Peter Rasmussen, M.D. 21Dept. of Neurological Surgery,CCF2Dept. of Neurology, CCFPROJECT SCIENTISTYounghua Dong, M.D.RESEARCH FELLOWSLjiljana Bengez, M.D., Ph.D.Edwin Cunningham, M.D.Young-Soo Kim, M.D.Alberts, M.J., Hademenos, G., Latchaw, R.E., Jagoda, A., Marler, J.R., Mayberg, M.R., Starke, R.D., etal. (2000) Recommendations for the establishment of primary stroke centers. Brain Attack Coalition.JAMA 283:3102-3109.Moon, C.T., Gajdusek, C., London, S., and M.R. Mayberg (2001) Expression of endothelial nitric oxidesynthase after exposure to perivascular blood. Neurosurgery 48:1328-1332.McAllister, M.S., Krizanac-Bengez, L., Macchia, F., Naftalin, R.J., Pedley, K.C., Mayberg, M.R., Marroni,M., Leaman, S., Stanness, K.A., and D. Janigro (2001) Mechanisms of glucose transport at the bloodbrainbarrier: an in vitro study. Brain Res. 904:20-30.Gajdusek, C., Onoda, K., London, S., Johnson, M., Morrison, R., and M. Mayberg (2001) Early molecularchanges in irradiated aortic endothelium. J. Cell Physiol. 188:8-23.Krieger, D.W., De Georgia, M.A., Abou-Chebl, A., Andrefsky, J.C., Sila, C.A., Katzan, I.L., Mayberg,M.R., and A.J. Furlan (2001) Cooling for acute ischemic brain damage (COOL AID): an open pilotstudy of induced hypothermia in acute ischemic stroke. Stroke 32:1847-1854.159