Louise D. McCullough, M.D.

Professor of Neurology and Neuroscience
Director of Stroke Research
Academic Office Location:
Neurology
University of Connecticut Health Center
263 Farmington Avenue
Farmington, CT 06030
Phone: 800-535-6232
860-679-7692
Website(s): Neuroscience Graduate Program

Education
DegreeInstitutionMajor
M.D.University of Connecticut School of MedicineMedicine
Ph.D.University of ConnecticutNeuroscience
M.A.University of ConnecticutExperimental Psychology
B.A.University of ConnecticutPsychology

Post-Graduate Training
TrainingInstitutionSpecialty
InternshipJohns Hopkins Bayview Medical CenterInternal Medicine
ResidencyJohns Hopkins HospitalNeurology (Chief 2000)
FellowshipJohns Hopkins UniversityCerebrovascular Disease, Neurology and Anesthesiology
Professional TrainingHartford HospitalPhysician Leadership Program

Awards
Name of Award/HonorAwarding Organization
Preclinical Teaching Award Medical Students
Medical Dean's Award in recognition of Outstanding Faculty mentoring in the Medical/Dental Student Summer Research Fellowship ProgramUConn School of Medicine
Volunteer Recognition AwardAmerican Heart Association
David Frederick Award for Excellence in Teaching
Invited Speaker for the International Stroke Meeting, 2008-2011 International Stroke Meeting
Invited Speaker American Neurological Association, 2008-2010 American Neurological Association
Outstanding Teaching Award in Basic Science Curriculum
Fellow American Heart Association
National and Hartford “Best Doctors” Recognition, 2007-2012
Top Doctor RecognitionHartford and National
Women’s Board Career Recognition Award American Heart Association
Princeton Attendee, 2004, 2006, 2008, 2010 Princeton University
Dr. Jay Slotkin Award for Excellence in Research
Achievement Award for Excellence in Research
Glasgow Award for Academic Achievement
Clinically, stroke is increasingly recognized as a sexually dimorphic disease. Most international databases demonstrate that women enjoy lower stroke incidence relative to men until advanced age. This native neuroprotection is lost after menopause, often attributed to loss of estrogen. It is equally well established that tissue damage and functional outcome after experimental brain injury are shaped by biologic sex. Emerging data suggest that cell death in brain may follow differing mechanistic paths depending on gender, in addition to sex steroid exposure. In our work we are attempting to discover the underlying mechanisms of these gender differences. We have recently found that a striking gender difference occurs in one basic pathway of cell death. A major mechanism of ischemia-induced neuronal cell death results from overstimulation of neuronal nitric oxide synthase (nNOS) leading to enhanced production of nitric oxide (NO), consequent peroxynitrite (ONOO) formation and nitrosative DNA damage. In response to this DNA damage, the energy consuming DNA repair enzyme poly ADP ribose polymerase-1 (PARP-1) is activated. The extensive damage that occurs during ischemia leads to exuberant energy consumption, mobilization of mitochondrial pro-apoptotic molecules and cell death However the evidence establishing NO toxicity/PARP-1 activation as a major cytotoxic mechanism has accumulated from studies utilizing exclusively male animals with deletions of nNOS (nNOS-/-) or PARP (PARP-/-) or mixed cell cultures. We have recently demonstrated that significant gender differences exist in this basic cell death pathway after an ischemic insult in vivo. Genetic deletion of nNOS or PARP-1, although neuroprotective in male animals, led to an exacerbation of damage in females after middle cerebral artery occlusion (MCAO). We have also found that similar gender differences exist at the cellular level. XY-derived (male) hippocampal slice cultures exhibited increased cell death after exposure to oxygen-glucose deprivation compared to those derived from XX (female) neurons.
Accepting Lab Rotation Students: Fall '13, Spring '14


Lab Rotation Projects

My primary research focus is the basic mechanisms involved in cerebral ischemia. Our major focus has been centered on examining how the male and female brain differ in their response to ischemia. We are also currently examining how to manipulate energy metabolism in the ischemic brain to promote neuronal survival after stroke.

Journal Articles

Book Chapters

  • Effects of gender and sex steroids on ischemic injury.
    McCullough LD, Koerner IP, Hurn PD Handb Clin Neurol 2008 Jan;149-69
  • Gender differences in stroke pathobiology: Therapeutic implications
    McCullough LD, Kofler J, Hurn PD Acute Stroke: Bench to Bedside 2006 Jan;
  • Intravenous and Intra-arterial TPA for Acute Stroke.
    Blakely J, Llinas, RH, McCullough, LD Stroke 2006 Jan;
  • Stroke in Women: The effect of Oral Contraceptives and Hormone Replacement on Stroke Risk.
    Cortese I and McCullough LD Stroke 2006 Jan;
  • The Savvy Woman Patient. How and Why Your Sex Impacts Your Health.
    McCullough LD and Hurn PD Society for Women's Health Research 2006 Jan;
  • Estrogen and Testosterone as Neuroprotectants in Stroke.
    Hurn PD, Ardelt AA, Alkayed NJ, Crain BJ, Hu W, Kearney ML, McCullough LD, Murphy SJ, Toung TJK, Traystman RJ, Wang MM. Pharmacology of Cerebral Ischemia 2002 Jan;
  • Cerebral Ischemia: Pathophysiology and Neuroprotection.
    Hurn PD, Alkayed NJ, Bhardwaj A, Koehler RC, Kirsch JR, Littleton-Kearney MT, McCullough LD, Murphy SJ, Rossberg MI, Toung TJ & Traystman RJ Yearbook of Intensive Care Medicine and Emergency Medicine 2001 Jan;
  • Vascular effects of estrogen in experimental stroke.
    Alkayed, NJ, McCullough LD, Littleton-Kearney M., Rusa R., Sampei, K., Sawada M., Goto S., Watanabe Y., Toung TJK, Crain BJ, Traystman RJ & Hurn, P.D. Intima Media Thickness: Watching the Arterial Risk. 2001 Jan;

Abstracts

  • Neonatal Testosterone Administration Provides Neuroprotection After Stroke In Adult Male Rats.
    Rebecca W. Persky, Fudong Liu, Gillian Weston, Stephanie Levy, Louise D. McCullough. Stroke 2011 Jan;42(3):e148
  • Social Isolation Worsens Stroke Outcome, Role of Nuclear Factor KappaB and Sex.
    Louise D McCullough, Jun Li, Fudong Liu, et al. Stroke 2011 Jan;42(93):e180
  • Age and Sex Related Differences in Experimental Stroke.
    Fudong Liu, Louise D. McCullough. University of Connecticut Aging Research Day, Program and Abstracts. 2010 Jan;
  • Cytochrome C-Caspase 3 Pathway Predominates in Cell Damage in Female Mice After Stroke.
    Fudong Liu, Mike Yuan, Louise D. McCullough, etc. Stroke 2009 Jan;40(4):E212-E213
  • Calpain-mediated proteolysis disrupts axonal membrane specialization following stroke.
    Dorothy P. Schafer, Fudong Liu, Louise D. McCullough. Stroke 2008 Jan;39(2):659-660
  • Differences in Infarct Volume in Young and Aging Mice Are Related to Differences in Edema Formation and IL-6 Expression.
    Fudong Liu, Rongwen Yuan, Louise D. McCullough. Stroke 2008 Jan;39(2):672
  • The polarized anonal cytoskeleton during neurodegeneration.
    Dorothy Schafer, Fudong Liu, Louise D. McCullough, et al. Journal of Neurochemistry 2007 Jan;102(Suppl.1):275

Editorials

Reviews