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 ischemic stoke. Specific areas we are interested in include:
- Acute ischemic stroke and reperfusion injury
- Cerebrovascular adaptation to pregnancy and preeclampsia/eclampsia
- Long-term cardiovascular consequences of preeclampsia.
Specific projects are described below:
Vascular protection for acute ischemic stroke
Ischemic stroke is the leading cause of disability and the fifth leading cause of death in the US, but the second worldwide. 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.
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.
Effect of preeclampsia and eclampsia on cognition and vascular function later in life
It is well-known that the consequences of preeclampsia and eclampsia extend far beyond pregnancy and are associated with excessive cardiovascular and cerebrovascular disease risk later in life, including a 9-fold increased risk of dying from myocardial
infarction and a 4- to 5-fold increased risk of stroke. Importantly, former preeclamptic and eclamptic women have poorer cognition and brain atrophy later in life, with increased white matter lesions on magnetic resonance imaging that positively correlate
with cognitive defects and decline. The effect of preeclampsia and eclampsia on memory and cognition suggests the hippocampus is adversely affected, a brain region that has a critical role in consolidation of long- and short-term memory and spatial
navigation. Our previous studies found that hippocampal arterioles (HAs), small brain arterioles that perfuse the hippocampus, were smaller and stiffer in a model of experimental preeclampsia (ePE) than HAs from normal late-pregnant animals that was
associated with mild cognitive impairment. In addition, ePE animals lacked a hyperemic response to seizure that caused greater neuronal injury. Thus, we are also investigating vascular mechanisms of hippocampal injury and cognitive impairment during
preeclampsia and eclampsia. We are interested in mechanisms by which HA remodeling and increased stiffness occurs in ePE and if preventing the vascular changes will prevent cognitive impairment. In addition, we are investigating the effect of prolonged
and recurrent seizure on hippocampal injury and if preventing HA remodeling will prevent injury during seizure. And lastly, we are investigating if the vascular and cognitive changes persist long-term (months postpartum) in ePE rats. This project
aims to provide a greater understanding of the mechanisms by which cognitive impairment occurs in women with preeclampsia and how seizure adversely affects the maternal brain.
National Institute of Neurologic Disorders and Stroke (NINDS) R01 NS45940-15
“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 NS093289-04
“Targeting Parenchymal Arterioles in Acute Stroke Treatment”
PI: Marilyn Cipolla, PhD
National Institute and Neurological Disorders and Stroke (NINDS) R01 NS108455-01
'Hippocampal arteriole remodeling and brain injury in preeclampsia and eclampsia'
PI: Marilyn Cipolla, PhD
AHA Predoctoral Award 19PRE34430175
'Mechanisms of Hypertension-induced Vasoconstriction in Leptomengeal Anastomoses'
Agency: American Heart Association, Total support: $53,688; 01/01/2018-12/31/20
PI: Zhaojin Li
P20 Centers of Biomedical Research Excellence (COBRE) (NGMS)
“Vermont Center for Cardiovascular and Brain Health”
PI: Mark Nelson, PhD and Mary Cushman, MD
Role: Project mentor for 2 Projects
American Heart Association Career Development Award 20CDA35310239
“Hippocampal Vascular Function in Chronic Hypertension and Post-Stroke Dementia”
PI: Abbie C. Johnson, PhD
TOTMAN MEDICAL RESEARCH TRUST
HONORS & AWARDS
- UVM Medical Alumni Association’s Distinguished Graduate Alumni Award, 2020
- Graduate Students Choice Lecturer, Department of Pharmacology, University of Mississippi (2017)
- 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)
- External Advisory Committee member to SPAN (NIH Stroke Preclinical Assessment Network), 2019-2022
- Chair, P01 Review SEP, ZNS1 SRB-A(30), February 2020
- Chair, Acute Neural Injury and Epilepsy study section, NIH, 2018-2020
- Chair, P01 Review SEP, ZNS1 SRB-A(25), July 2019
- Program Director, Society for Reproductive Investigation annual meeting, 2017-2018
- Panelist, NIH workshop on Translational Stroke Research: Vision and Opportunities, 2016
- Section chair, NIH workshop on Small Blood Vessels: Big Health Problems, Environmental Influences, 2015
- Panelist, NIH Workshop on Perinatal Stroke, 2015
- NINDS representative to Multicenter Preclinical Animal Research Team (Multi-PART)
- Board of Directors, Cardiovascular Research Institute of Vermont (CVRI)
- Advisory committee, Women’s Reproductive Health Research (WRHR), NICHD
- Chair, AHA Founder’s Affiliate Research Committee, 2013-2014
- Board of Directors, AHA Founder’s Affiliate, 2013-2014
- Council member, Society for Reproductive Investigation, 2012-2015
- Board of Directors, International Society for Cerebral Blood Flow Metabolism, 2011-2015
- Program committee, Brain 2015 meeting
- Program committee, Society for Reproductive Investigation, 2012-present
- Scientific Advisory Committee, International Symposium on Resistance Arteries
- Scientific Planning Committee, Collateral Perfusion annual meeting
Translational Stroke Research
Journal of Cerebral Blood Flow and Metabolism
Stroke Section Editor on Vascular Biology
CIPOLLA LAB HONORS & 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
University of Vermont CVRI Travel Award, Brain, Berlin, Germany, 2017 – Kelvin Chan, PhD
University of Vermont CVRI Travel Award,
Society for Reproductive Investigation Annual Meeting, 2016, Montreal, Canada – Abbie Chapman Johnson, PhD
University of Vermont CVRI Travel Award, International Society for the Study of Hypertension in Pregnancy, 2016, Sao Paulo, Brazil
– Abbie Chapman Johnson, PhD
AHA Predoctoral Fellowship Award - Zhaojin (Scarlett) Li
CVRI Career Development Award, 2019 - Zhaojin (Scarlett) Li
Stroke Basic Science Award, American Heart Association Internation Stroke Conference 2020 - Zhaojin (Scarlett)
First Place Winner, Viridis Montis Early Career Investigator Challenge in Cardiovascular Disease 2020 - Zhaojin (Scarlett) Li
UVM Graduate Alumni Dissertation Fellowship Award 2020 – Zhaojin (Scarlett) Li
SELECTED PUBLICATIONS (2015-2020)
Johnson AC, Li Z, Orfila JE, Herson PA, Cipolla MJ (2020): Hippocampal Network Dysfunction as a Mechanism of Early-Onset Dementia After Preeclampsia and Eclampsia. Progress in Neurobiology (Online ahead of print).
Li Z, Lindner D, Bishop N, and Cipolla MJ (2020): Angiotensin converting enzyme inhibition reverses vasoconstriction and impaired dilation of pial collaterals in chronic hypertension. Hypertension 76(1):226-235. PMC7289681
Cipolla MJ and Chan SL (2020). Impact of Acute and Chronic Hypertension on Changes in Pial Collateral Tone in vivo During Transient Ischemia. Hypertension Sep;76(3):1019-1026.
Beard D, Li Z, Schneider A, Couch Y, Cipolla MJ, and Buchan A (2020). Rapamycin Induces an eNOS Dependent Increase in Brain Collateral Perfusion in Wistar and Spontaneously Hypertensive Rats. Stroke Sep;51(9):2834-2843.
Johnson AC, Miller JE, and Cipolla MJ (2020): Memory Impairment in Spontaneously Hypertensive Rats is Associated with Hippocampal Hypoperfusion and Hippocampal Vascular Dysfunction. J Cerebr Blood Flow Metab Apr;40(4):845-859.
Herisson F, Zhou IY, Mawet J, Du E, Hajizadeh B, Qin T, Cipolla MJ, Sun PZ, Ayata C, Rost N (2019): Posterior reversible encephalopathy syndrome in stroke-prone spontaneously hypertensive rats on high-salt diet. J Cerebr Blood Flow Metab Jul;39(7):1232-1246.
Chan SL, Nelson MT and Cipolla MJ (2019): TRPV4 channels are involved in diminished myogenic tone in brain parenchymal arterioles in response to chronic hypoperfusion in mice. Acta Physiologica Feb;225(2):e13181. NIHMSID: 1005007.
Li Z, Tremble SM, Cipolla MJ. (2018) Implications for understanding ischemic stroke as a sexually dimorphic disease: the role of pial collateral circulations. American Journal of Physiology. Heart and Circulatory Physiology 315(6):H1703-H1712.
Li Z, Bishop N, Chan S, Cipolla MJ. (2018) Effect of TTC Treatment on Immunohistochemically Quantitation of Collagen IV in Rats Brains after Stroke. Springer. Translational Stroke Research 9(5):499-505.
Cipolla MJ, Liebeskind DS, Chan SL (2018). The importance of comorbidities in ischemic stroke: Impact of hypertension on the cerebral circulation. J Cereb Blood Flow Metab. 38(12):2129-2149.
Chan SL, Bishop N, Li Z, Cipolla MJ (2018). Inhibition of PAI (Plasminogen Activator Inhibitor)-1 Improves Brain Collateral Perfusion and Injury After Acute Ischemic Stroke in Aged Hypertensive Rats. Stroke 49(8):1969-1976.
Johnson AC, Cipolla MJ. (2018) Impaired function of cerebral parenchymal arterioles in experimental preeclampsia. Microvasc Res. 119:64-72.
Merhi Z, Buyuk E, Cipolla MJ. (2018) Advanced glycation end products alter steroidogenic gene expression by granulosa cells: an effect partially reversible by vitamin D. Mol Hum Reprod. 24(6):318-326.
Brussé IA, van den Berg CB, Duvekot JJ, Cipolla MJ, Steegers EAP, Visser GH (2018). Visual evoked potentials in women with and without preeclampsia during pregnancy and postpartum. J Hypertens 36(2):319-325.
Johnson AC, Hammer ES, Sakkaki S, Tremble SM, Holmes GL, Cipolla MJ (2018). Inhibition of blood-brain barrier efflux transporters promotes seizure in pregnant rats: Role of circulating factors. Brain Behav Immun 67:13-23.
Cipolla, MJ, Linfante I, Abuchowski A, Jubin R, Can SL (2018). Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (SanguinateTM) in spontaneously hypertensive rats.
J Cereb Blood Flow Metab 38(5):755-766.
Bosetti F, Koenig JI, Ayata C, Back SA, Becker K, Broderick JP, Carmichael ST, Cho S, Cipolla MJ, Corbett D, Corriveau RA, Cramer SC, Ferguson AR, Finklestein SP, Ford BD, Furie KL, Hemmen TM, Iadecola C, Jakeman LB, Janis S, Jauch EC, Johnston KC, Kochanek
PM, Kohn H, Lo EH, Lyden PD, Mallard C, McCullough LD, McGavern LM, Meschia JF, Moy CS, Perez-Pinzon MA, Ramadan I, Savitz SI, Schwamm LH, Steinberg GK, Stenzel-Poore MP, Tymianski M, Warach S, Wechsler LR, Zhang JH, Koroshetz W (2017). Translational
Stroke Research: Vision and Opportunities. Stroke 48(9):2632-2637.
Chan, SL, Cipolla, MJ (2017). Treatment with low dose fasudil for acute ischemic stroke in chronic hypertension. J Cereb Blood Flow Metab 37(9):3262-3270.
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 (2017). Altered hippocampal arteriole structure and function in a rat model of preeclampsia: Potential role in impaired seizure-induced hyperemia. J Cereb Blood Flow Metab 37(8):2857-2869.
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 Sep/122(10):1403-9.
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.
PEOPLE IN THE LAB
ABBIE CHAPMAN JOHNSON, PhD
Dept. of Neurological Sciences
Involvement of the hippocampal vasculature in cognitive decline
associated with cardiovascular and cerebrovascular diseases,
including chronic hypertension and ischemic stroke
EMMETT WHITAKER, M.D.
Associate Professor of Anesthesiology, Neurological Sciences, & Pediatrics
University of Vermont Larner College of Medicine
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
LABORATORY RESEARCH TECHNICIANS
CIPOLLA LAB ALUMNI
Erica Hammer, M.D.
Isabella Canavero, M.D.
Hilda Ahnstedt, Ph.D.
Devon P. Lindner
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