University of Vermont

College of Medicine

Department of Neurological Sciences

marilyn cipolla lab department of neurological sciences university of vermont

Marilyn J. Cipolla, Ph.D.
Professor, Department of Neurological Sciences

 

 

 

 

 

Joint appointments:

Obstetrics, Gynecology & Reproductive Sciences

Pharmacology

Education:

B.S. Electrical Engineering, University of Vermont, 1988
M.S., Cell and Molecular Biology, University of Vermont College of Medicine, 1994
Ph.D., Cell and Molecular Biology, University of Vermont College of Medicine, 1997

Research

Our laboratory studies the cerebral circulation under physiological and pathological conditions. In particular, we are interested in how changes in cerebrovascular structure and function affect cerebral blood flow regulation and hemodynamics in ways that could promote brain injury. In addition, we are interested in blood-brain barrier properties and how changes in permeability to water or solutes can promote injury, including seizure and white matter lesions. Specific areas we are interested in include:

  • Acute ischemic stroke and reperfusion injury
  • Mechanisms and treatment of small vessel disease
  • Cerebrovascular adaptation to pregnancy and preeclampsia/eclampsia

Specific projects are described below:

Vascular protection for acute ischemic stroke

Ischemic stroke is the leading cause of disability and the fourth leading cause of death in the US. The ability of the cerebral circulation to function and supply oxygen and nutrients to the brain after stroke defines the extent of reperfusion and ultimately determines stroke outcome. In our lab, we are focused on studying how ischemia and reperfusion influences the normal behavior of the cerebral arteries and arterioles. We use an established model of stroke - the middle cerebral artery occlusion model MCAO) - to investigate underlying mechanisms of damage to the cerebral vasculature and what treatments will prevent the damage, ie., provide vascular protection.

Ischemic small vessel disease (SVD)

Cerebral SVD is a common age- and hypertension-related vasculopathy of the penetrating and parenchymal arterioles in the brain that causes lacunar stroke, white matter lesions and vascular dementia. The major pathology underlying SVD involves hypertension-induced structural alterations in the parenchymal arterioles, including thickening of the vessel wall and reduced lumen size that leads to loss of autoregulation and a state of chronic hypoperfusion of the white matter. Localized increased blood-brain barrier (BBB) permeability of PA is also involved in SVD pathology by causing focal edema and passage of damaging proteins and serum constituents into the brain parenchyma that can damage white matter. Our goal is to understand how parenchymal arterioles are uniquely affected by chronic hypertension to promote SVD and to selectively treat PA to reverse these detrimental effects.

Adaptation of the cerebral circulation to pregnancy and preeclampsia

Hypertension is a serious complication of pregnancy that occurs in ~5-8% of all pregnancies. While numerous organs are affected by hypertension in pregnancy, cerebrovascular involvement is the direct cause of death in approximately 40% of patients. Neurologic complications can occur in preeclampsia and cause severe and persistent headaches, uncontrolled vomiting, seizure and coma. The major cerebrovascular changes that occur have been shown to be similar to hypertensive encephalopathy in which an acute elevation in blood pressure overcomes the myogenic vasoconstriction of the cerebral arteries and arterioles causing autoregulatory failure, hyperperfusion and edema formation. In addition, blood-brain barrier disruption can cause passage of damaging serum proteins and constituents into the brain parenchyma, causing seizure. However, a fair number of women have seizure during pregnancy at normal blood pressures with seemingly uncomplicated pregnancy. Thus, we are interested in how both normal pregnancy and hypertension in pregnancy affect the cerebral circulation in ways that promote neurologic symptoms, including seizure.

Funding

National Institute of Heart Lung and Blood Institute (NHLBI) P01 HL95488-01
“Calcium signaling in the cerebrovascular unit in health and disease”
PI: Mark T. Nelson, PhD
Role: PI on Project 3: “Cerebrovascular function during ischemia and reperfusion"

National Institute of Neurologic Disorders and Stroke (NINDS) R01 NS45940
“The role of the blood-brain barrier in seizure during pregnancy and preeclampsia”
PI: Marilyn Cipolla, PhD

National Institute of Heart Lung and Blood Institute (NHLBI) grant HL071944-05
“Pre-pregnancy Phenotype and Predisposition to Preeclamplsia”
PI: Ira M. Bernstein, MD

Preeclampsia Vision Award

PI:  Erica Hammer, MD

Sponsor:  Marilyn Cipolla, PhD

Totman Medical Research Trust

Georgio Pardi Foundation

Honors and Awards

  • Invited member, Gravida International College, National Center for Growth and Development, University of Auckland 

  • Fellow, AHA Stroke Council (2012)
  • Jacob de Back Lecturer, University of Groningen, The Netherlands (2011)
  • President's Achievement Award - Society for Gynecologic Investigation (2010)
  • Giorgio Pardi Award (2009)
  • Fellow, Cardiovascular Section of the American Physiologic Society (2007)
  • Center for Gender Studies Inaugural Lecturer, Oregon Health & Sciences University, 2007
  • Established Investigator of the AHA (2004)
  • Fellow, AHA Council for High Blood Pressure Research (2001)
  • Young Investigator Award, Perinatal Research Society, 1999

  • James A. Shannon Director's Award, NIH, Office of the Director (1998)

Professional Activities

Board of Directors, Cardiovascular Research Institute of Vermont (CVRI) 

Chair, NIH Workshop on Small Blood Vessels:  Big Health Problems 

Advisory committee, Women’s Reproductive Health Research (WRHR), NICHD 

Advisor, WHO Maternal and Child Health Branch 

Scientific Advisory Committee, International Symposium on Resistance Arteries, 2014

NINDS Representative, Multicenter Preclinical Animal Research Team

Council member, Society for Gynecologic Investigation
Board of Directors, International Society for Cerebral Blood Flow Metabolism
Chair, AHA Founder’s Affiliate Research Committee, 2013-2014
NINDS Stroke Progress Review Group (SPRG)
Program Committee, Brain 2015 Meeting

Editorial Boards

Stroke

Hypertension
Journal of Cerebral Blood Flow and Metabolism

Translational Stroke Research

Frontiers in Physiology
Journal of Cardiovascular Pharmacology and Therapeutics

Cipolla Lab Trainee Honors and Awards

President’s Presenters Award, Society for Gynecologic Investigation:

  • Anna Euser, PhD, 2006
  • Marjon Wiegman, 2008
  • Abbie Chapman Johnson, 2014

Joseph B. Warshaw Scholarship Award - Anna Euser, PhD
AHA Predoctoral Fellowship Award - Anna Euser, PhD
SGI 2010 Poster Award - Laurie Amburgey, MD
NGP Annual Retreat Best Student Oral Presentation - Abbie Chapman Johnson
AHA Predoctoral Fellowship Award - Abbie Chapman Johnson
Preeclampsia Vision Award 2014 – Erica Hammer, MD
Zuspan Award 2014 – Abbie Chapman Johnson

Selected Publications (2011-2014)

2014

Johnson AC, Tremble SM, Chan SL, Moseley J, LaMarca B, Nagle KJ, Cipolla MJ (2014):  Magnesium Sulfate Treatment Reverses Seizure Susceptibility and Decreases Neuroinflammation in a Rat Model of Severe Preeclampsia.  PLoS One (In Press).

Johnson AC and Cipolla MJ (2014):  The cerebral circulation during pregnancy:  Adapting to maintain normalcy.  Physiology (In Press).

Merhi Z, Doswell A, Cipolla MJ (2014):  Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells.  J Clin Endo & Metab (In Press).

Schreurs MPH, Cipolla MJ, Al-Nasiry S, Peeters LLH, Spaanderman MEA (2014):  Formerly eclamptic women have lower nonpregnant blood pressure compared to formerly preeclamptic women. BJOG (Under Revision).

Wallace K, Tremble SM, Owens MY, Morris R, Cipolla MJ (2014):  Plasma From Patients With HELLP Syndrome Increases Blood-Brain Barrier Permeability. Repro Sci (In Press).

Cipolla, MJ, Chan SL, Sweet J, Tavares MJ, Gokina N, Brayden JE (2014):  Postischemic Reperfusion Causes Smooth Muscle Calcium Sensitization and Vasoconstriction of Parenchymal Arterioles. Stroke 45 (8):  2425-30.

Cipolla MJ, Sweet JG, Chan SL, Tavares MJ, Gokina NI, Brayden JE (2014): Increased Pressure-induced Tone in Rat Parenchymal Arterioles vs. Middle Cerebral Arteries: Role of Ion Channels and Calcium Sensitivity. J Appl Physiol 117 (1):  53-9.

Schreurs MP, Cipolla MJ. (2014): Cerebrovascular dysfunction and blood-brain barrier permeability induced by oxidized LDL are prevented by apocynin and magnesium sulfate in female rats. J Cardiovasc Pharmacol 63(1):33-9.

2013

Palomares SM, Cipolla MJ (2013): Myogenic Tone as a Therapeutic Target for Ischemic Stroke. Curr Vasc Pharmacol (In Press).

Gokina NI, Chan SL, Chapman AC, Oppenheimer K, Jetton TL, Cipolla MJ (2013): Inhibition of PPARγ during rat pregnancy causes intrauterine growth restriction and attenuation of uterine vasodilation. Front Physiol (4): 184.

Cipolla MJ, Sweet JG, Gokina NI, White SL, Nelson MT (2013): Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: role of ET-1-induced peroxynitrite generation. J Cerebral Blood Flow Metab 33 (10): 1486-92.

Chan SL, Sweet JG, Cipolla MJ (2013): Treatment for cerebral small vessel disease: effect of relaxin on the function and structure of cerebral parenchymal arterioles during hypertension. FASEB J 27 (10): 3917-27.

Chapman AC, Cipolla MJ, Chan SL (2013): Effect of Pregnancy and Nitric Oxide on the Myogenic Vasodilation of Posterior Cerebral Arteries and the Lower Limit of Cerebral Blood Flow Autoregulation. Repro Sci 20 (9): 1046-54.

Cipolla MJ (2013): The adaptation of the cerebral circulation to pregnancy: mechanisms and consequences. J Cereb Blood Flow Metab 33(4): 465-78.

Van der Wijk AE, Scheurs MP, Cipolla MJ (2013): Pregnancy causes diminished myogenic tone and outward hypotrophic remodeling of the cerebral vein of Galen. J Cereb Blood Flow Metab 33(4): 542-9

Schreurs MPH and Cipolla MJ (2013): Pregnancy enhances the effects of hypercholesterolemia on posterior cerebral arteries. Repro Sci 20(4): 391-9

Schreurs MP, Hubel CA, Bernstein IM, Jeyabalan A, Cipolla MJ (2013): Increased oxidized low-density lipoprotein causes blood-brain barrier disruption in early-onset preeclampsia through LOX-1. FASEB J 27(3): 1254-63

2012


Cipolla MJ, Bishop N, Chan S-L (2012): Effect of pregnancy on autoregulation of cerebral blood flow in anterior and posterior cerebrum. Hypertension 60(3):705-11.

Morales Palomares S, Sweet JG and Cipolla MJ (2012): Acute rosiglitazone during reperfusion after hyperglycemic stroke is neuroprotective but not vascular protective. Transl Stroke Res. 3 (3): 390-396

Schreurs M, Houston E, May V, Cipolla MJ (2012): The adaptation of the blood-brain barrier to VEGF and PLGF during pregnancy. FASEB J 26(1):355-62.

Chan S-L and Cipolla MJ (2012): Determination of PPARgamma Activity in Adipose Tissue and Spleen. J Immunoassay Immunochem 33(3):314-324.

Cipolla MJ, Pusic AD, Grinberg YY, Chapman AC, Houston EM, Poynter ME, Kraig RP (2012): Pregnant Serum Causes Neuroinflammation and Seizure Activity via TNFa. Exp Neurol 234(2):398-404.

Morales Palomares S and Cipolla MJ (2012): Peroxynitrite decomposition with FeTMPyP improves plasma-induced vascular dysfunction and infarction during mild but not severe hyperglycemic stroke. J Cerebr Blood Flow Metab 32(6):1035-1045.

Cipolla MJ, Pusic AD, Grinberg YY, Chapman AC, Poynter ME, Kraig RP (2012): Pregnant serum induces neuroinflammation and seizure activity via TNFα. Exp Neurol 234(2):398-404.

Mandala M, Pedatella AL, Morales Palomares S, Cipolla MJ, Osol G (2012): Maturation is associated with changes in cerebral artery biomechanical properties and reduced vascular tone. Acta Physiol 205(3):363-371.

2011

Cipolla MJ, Sweet JA, Chan S-L (2011) : Cerebral vascular adaptation to pregnancy and its role in the neurological complications of eclampsia. J Appl Physiol 110(2):329-39.

Chan S-L and Cipolla MJ (2011): Relaxin activates PPARγ and causes selective outward remodeling of brain penetrating arterioles. FASEB J 25(9):3229-39.

Cipolla MJ, Huang Q, Sweet JA (2011): Inhibition of protein kinase Cß reverses increased blood-brain barrier permeability and prevents edema formation in vivo during hyperglycemic stroke. Stroke 42: 3252-3257.

Cipolla MJ, Houston EM, Kraig RP and Bonney EA (2011): Differential effects of low-dose endotoxin on the cerebral circulation during pregnancy. Reprod Sci 18 (12):1211-1221.

Cipolla MJ and Kraig RP (2011): Invited Review: Seizures in women with preeclampsia: Mechanisms and management. Fetal and Mat Med Rev 22(2):91-108.

Morales Palomares S and Cipolla MJ (2011): Invited Review: Vascular protection following ischemia and reperfusion J Neurol Neurophysiol 20;pii: S1- 004.

For a complete list of Dr. Cipolla's publications, please visit PubMed.

People in the Lab

 

Research Scientists

Siu-lung (Kelvin) Chan, Ph.D.

B.S. Biology, Chinese University of Hong Kong

Ph.D. Pharmacology, Chinese University of Hong Kong

 

Fellows

Erica Hammer, M.D.

B.S. Biology & Neuroscience, Trinity College

M.D. University of Vermont College of Medicine

 

Post-Doctoral Fellows

Hilda Ahnstedt, Ph.D.

M.S. Chemical Biology, Linköping University, Sweden

Ph.D. Clinical Medicine, Vascular Research, Lund University, Sweden

 

 

Laboratory Research Technicians

 

 

Julie Sweet

B.S. Molecular Biology and Biochemistry, Middlebury College

Sarah M. Tremble

B.S. Biology, Saint Michael's College

 

 

Graduate Students

Abbie Chapman Johnson

B.S. Biology, University of Maine at Orono

Current student in the Neuroscience Graduate Program, University of Vermont

 

 

Cipolla Lab

Department of Pharmacology Annual Research Retreat

Trapp Family Lodge, Stowe VT

November 2014

 

 

 

 

 

 

Last modified December 04 2014 12:24 PM