Marilyn J. Cipolla, Ph.D.
Professor, Department of Neurological Sciences
Obstetrics, Gynecology & Reproductive Sciences and Pharmacology
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
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.
National Institute of Neurologic Disorders and Stroke (NINDS) R01 NS45940-10
“The role of the blood-brain barrier in seizure during pregnancy and preeclampsia”
PI: Marilyn Cipolla, PhD
National Institute of Neurologic Disorders and Stroke (NINDS) R01 NS093289-01
“Targeting Parenchymal Arterioles in Acute Stroke Treatment”
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
Totman Medical Research Trust
Honors and Awards
- University Scholar, University of Vermont (2015)
- Fellow, AHA Stroke Council (2012)
- Jacob de Back Lecturer, University of Groningen, The Netherlands (2011)
- President's Achievement Award - Society for Gynecologic Investigation (2010)
- President, Perinatal Research Society (2010)
- Giorgio Pardi Award (2009)
- Fellow, Cardiovascular Section of the American Physiologic Society (2007)
- Center for Gender Studies Inaugural Lecturer, OHSU, (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)
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
NINDS Representative, Multicenter Preclinical Animal Research Team
Chair, AHA Founder’s Affiliate Research Committee, 2013-2014
NINDS Stroke Progress Review Group (SPRG)
Program Committee, Brain 2015 Meeting
Program Committee, Society for Reproductive Investigation
Program Director, Society for Reproductive Investigation, 2018
Planning Committee, Collaterals, 2017
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, MD, PhD, 2006
- Marjon Wiegman, MD, PhD, 2008
- Abbie Chapman Johnson, PhD, 2014
Joseph B. Warshaw Scholarship Award - Anna Euser, MD, PhD
AHA Predoctoral Fellowship Award - Anna Euser, MD, PhD
SGI 2010 Poster Award - Laurie Amburgey, MD
NGP Annual Retreat Best Student Oral Presentation - Abbie Chapman Johnson, PhD
AHA Predoctoral Fellowship Award - Abbie Chapman Johnson, PhD
Preeclampsia Foundation Vision Award 2014 – Erica Hammer, MD
Zuspan Award 2014 – Abbie Chapman Johnson, PhD
University of Vermont College of Medicine Summer Research Merit Award 2015: Patrick Cruden
SRI 2016 Poster Award – Abbie Chapman Johnson, PhD
Selected Publications (2013-2017)
Johnson AC, Hammer ES, Sakkaki S, Tremble SM, Holmes GL, Cipolla MJ (2017). Inhibition of blood-brain barrier efflux transporters promotes seizure in pregnant rats: Role of circulating factors. Brain Behav Immun (In Press).
Chan, SL, Cipolla, MJ (2017). Treatment with low dose fasudil for acute ischemic stroke in chronic hypertension. J Cereb Blood Flow Metab (In Press).
Cipolla, MJ, Linfante I, Abuchowski A, Jubin R, Can SL (2017). Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (SanguinateTM) in spontaneously hypertensive rats. J Cereb Blood Flow Metab (In Press).
Cipolla MJ, Biller J. (2017). Persistent brain injury after preeclampsia. Neurology. 88(13):1216-1217.
Cipolla MJ, Sweet JG, Chan SL (2017). Effect of hypertension and peroxynitrite decomposition with FeTMPyP on CBF and stroke outcome. J Cereb Blood Flow Metab. 37(4):1276-1285
Johnson AC, Cipolla MJ (2016). Altered hippocampal arteriole structure and function in a rat model of preeclampsia: Potential role in impaired seizure-induced hyperemia. J Cereb Blood Flow Metab (In Press).
Bosetti F, Galis ZS, Bynoe MS, Charette M, Cipolla MJ, Del Zoppo GJ, Gould D, Hatsukami TS, Jones TL, Koenig JI, Lutty GA, Maric-Bilkan C, Stevens T, Tolunay HE, Koroshetz W (2016). Small Blood Vessels: Big Health Problems?": Scientific Recommendations of the National Institutes of Health Workshop. J Am Heart Assoc 5(11). pii: e004389
Linfante I, Cipolla MJ (2016). Improving Reperfusion Therapies in the Era of Mechanical Thrombectomy. Transl Stroke Res 7(4):294-302.
Ahnstedt H, Sweet J, Cruden P, Bishop N, Cipolla MJ (2016). Effects of Early Post-Ischemic Reperfusion and tPA on Cerebrovascular Function and Nitrosative Stress in Female Rats. Transl Stroke Res7(3):228-38.
Chan SL, Sweet JG, Bishop N, Cipolla MJ (2016). Pial Collateral Reactivity During Hypertension and Aging: Understanding the Function of Collaterals for Stroke Therapy. Stroke 47(6):1618-25.
Merhi Z, Thornton K, Bonney E, Cipolla MJ, Charron MJ, Buyuk E (2016). Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1. J Assist Reprod Genet 33(4):535-43.
Babi MA, Gorman MJ, Cipolla MJ, Allen G, Al Jerdi S2, Clouser R, Commichau C (2016): Ondansetron-related hemorrhagic posterior reversible encephalopathy syndrome (PRES) following gastric bypass. Springerplus 5:18. doi: 10.1186/s40064-015-1644-9. eCollection 2016.
Canavero I, Sherburne HA, Tremble SM, Clark WM, Cipolla MJ (2016). Effects of Acute Stroke Serum on Non-Ischemic Cerebral and Mesenteric Vascular Function. Transl Stroke Res 7(2):156-65.
Ahnstedt H, McCullough LD, Cipolla MJ (2016). The Importance of Considering Sex Differences in Translational Stroke Research. Transl Stroke Res 7(4):261-73).
Sweet JG, Chan S-L, and Cipolla MJ (2015): Effect of Hypertension and Chronic Hypoperfusion on Brain Parenchymal Arteriole Structure and Function. J Appl Physiol 119(7):817-23.
Johnson AC, Nagle KJ, Tremble SM, Cipolla MJ (2015): The Contribution of Normal Pregnancy to Eclampsia. PLoS One 10 (7): e0133953.
Hammer ES, Cipolla MJ (2015): Cerebrovascular Dysfunction in Preeclamptic Pregnancies. Curr Hypertens Rep (8): 575.
Schreurs MPH, Cipolla MJ, Al-Nasiry S, Peeters LLH, Spaanderman MEA (2015): Formerly eclamptic women have lower nonpregnant blood pressure compared to formerly preeclamptic women. BJOG (In Press).
Johnson AC and Cipolla MJ (2015): The cerebral circulation during pregnancy: Adapting to maintain normalcy. Physiology 30(2): 139-147.
Wallace K, Tremble SM, Owens MY, Morris R, Cipolla MJ (2015): Plasma From Patients With HELLP Syndrome Increases Blood-Brain Barrier Permeability. Repro Sci 22(3): 278-84.
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 9 (11): e113670.
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 63(1): 33-39.
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.
Palomares SM, Cipolla MJ (2014): Myogenic Tone as a Therapeutic Target for Ischemic Stroke. Curr Vasc Pharmacol 12(6): 788-800.
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
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.
For a complete list of Dr. Cipolla's publications, please visit PubMed.
People in the Lab
Siu-lung (Kelvin) Chan, Ph.D.
B.S. Biology, Chinese University of Hong Kong
Ph.D. Pharmacology, Chinese University of Hong Kong
Abbie Chapman Johnson, Ph.D.
B.S. Biology, University of Maine at Orono
Ph.D. Neuroscience, University of Vermont
Zhaojin (Scarlett) Li, M.S.
B.S. Medical Laboratory Technology, Southern Medical University, China
M.S. Biochemistry & Molecular Biology, Georgetown University
Senior Laboratory Research Technician
Sarah M. Tremble
B.S. Biology, Saint Michael's College
Cipolla Lab Alumni
B.S. Biochemistry & B.A. Math, University of Rochester
B.S. Molecular Biology and Biochemistry, Middlebury College
Erica Hammer, M.D.
B.S. Biology & Neuroscience, Trinity College
M.D. University of Vermont College of Medicine
Current student at Dartmouth College
Isabella Canavero, M.D.
M.D. University of Pavia Medical School, Italy
Hilda Ahnstedt, Ph.D.
M.S. Chemical Biology, Linköping University, Sweden
Ph.D. Clinical Medicine, Vascular Research, Lund University, Sweden
B.S. Biology, Santa Clara University
M.D. Candidate, University of Vermont College of Medicine, Class of 2018
March for Science
April 22nd, 2017