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Medicine

Professor Roxana O Carare MD, PhD

Professor of Clinical Neuroanatomy, Equality and Diversity Lead

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Roxana Carare is a medically qualified Professor of Clinical Neuroanatomy and experimental neuropathology in the University of Southampton. Having graduated in general medicine in 1994 in Bucharest, Roxana completed her PhD in experimental neuropathology in 2006, in the University of Southampton, UK. The main international recognition for Roxana Carare has come from the neuroanatomy and neuropathology interdisciplinary research she leads, demonstrating the unique lymphatic drainage pathways by which fluid and soluble amyloid are eliminated from the brain along basement membranes within the walls of cerebral capillaries and arteries (Intramural Periarterial Drainage Pathways, IPAD).

The focus of Roxana’s research is to manipulate the intramural periarterial drainage pathways to improve the clearance of amyloid and interstitial fluid from the ageing brain, preventing neurodegenerative and neurovascular diseases

Qualifications

Medical Doctor (MD), Faculty of Medicine, University Carol Davila, Bucharest (1994)

PhD, University of Southampton (2006)

Appointments held

Clinical House Officer Clinical in Medicine, Surgery, Paediatrics, Romanian Hospitals: 1995-1996

Clinical Attachments in Surgery, Care of the Elderly, Hospitals in UK and Rep of Ireland: 1996-1997

Teaching Assistant in Human Morphology, School of Medicine, University of Southampton:1998-2001

Lecturer in Anatomy, Faculty of Medicine,University of Southampton: 2001-2008

Lecturer in Clinical Neurosciences, Faculty of Medicine, University of Southampton: 2008-2011

Senior Lecturer in Clinical Neurosciences, Faculty of Medicine, University of Southampton:2011-2014

Associate Professor Clinical Neurosciences, Faculty of Medicine, University of Southampton: 2014-2016

Professor of Clinical Neuroanatomy, Faculty of Medicine, University of Southampton: 2016-present

Other roles and activities

Fellow of the Higher Education Academy. Chair of the Steering Committee for Women in Science, Engineering and Technology in the University of Southampton, Visiting Knowledge Exchange Fellow, University of Winchester, Home Office Licensed Teacher of Anatomy. Honorary Consul for Romania. Member of: PRIME- International Medical Education, British Pathological Society, Association for the Study of Medical Education, British Neuroscience Association, British Neuropathological Society, Federation of European Neuroscience Societies, International Brain Research Organisation, British Association of Clinical Anatomists, Anatomical Society, International Alzheimer’s Disease Forum, Association for the Study of Medical Education. Member of the Scientific Committee for Cerebral Amyloid Angiopathy 2014. Member of Scientific Committee for Vas-Cog 2015. Invited member of Cerebral Autoregulation Research Network. Associate Editor Frontiers in Ageing Neuroscience; Fluids and Barriers in the CNS, Romanian Medical Journal. Reviewer for Acta Neuropathologica, Neuropathology and Applied Neurobiology, Clinical Anatomy, Experimental Neurology, Alzheimer’s Society, Alzheimer’s Research UK, EU Commission, Brain Canada. Member of British Neuropathological Society Academic Committee; Organising Committee Alzheimer’s Disease International 2016, Member of Pool of Experts BBSRC, Committee Member for the USA National Plan to address Alzheimer’s disease, NIH, 2016.

Prizes

Best research images at the 2011 Transmission Electron Microscopy British Society meeting; Vice-Chancellor Award for Best Teacher, University of Southampton, 2013; Best poster (senior author) Alzheimer’s Research UK 2014, 3rd prize poster Glia Magdeburg (Germany), 2014. Staff Achievement Award, University of Southampton 2014; supervisor for Abby Keable who won best oral presentation British Association of Clinical Anatomists, 2015; Dementia Leader Award, Alzheimer’s Society 2015, 1st prize Anatomical Society 2015, Venus Influential Woman of the Year 2016.

Research interests

The international recognition and unique contributions from the research that Roxana leads have derived from her interdisciplinary research demonstrating (i) the unique pathways by which fluid and soluble waste substances are eliminated from the brain along thin proteins layers (basement membranes) within the walls of cerebral capillaries and arteries; (ii) how this elimination pathway fails with advancing age, genotype, diet and following immunization against amyloid-β representing thus a significant factor in the pathogenesis of Alzheimer’s disease.

Research projects
  1. Innervation of cerebral arteries is key to maintenance of efficient clearance and flow. This project funded by Alzheimer’s Research UK in collaboration with Dr Cheryl Hawkes (Open University) tests the hypothesis that loss of perivascular innervation by cholinergic neurons leads to dysfunctional regulation of vascular tone, thereby reducing the motive force for perivascular drainage of Aβ leading to a worsening of cerebral amyloid angiopathy. Researcher: Mrs Maureen Gatherer

  2. Based on results from mathematical modelling performed by the interdisciplinary researchers in my group (Roxana Aldea, Prof Giles Richardson), we now know that the motive force for perivascular clearance is provided by spontaneous vasomotion resulting from the intrinsic contractions of pericytes and cerebrovascular smooth muscle cells and not by the pulsations derived from cardiac cycle (Dr Alexandra Diem, Prof Neil Bressloff). Collaborations are in place with senior neuroradiologists in University College London and Leiden, The Netherlands to demonstrate in vivo in real time using MRI, the features of the motive force for efficient intramural perivascular clearance and correlate this with findings in different stages of Alzheimer’s disease and mild cognitive impairment. This could be the first marker for impaired clearance of cerebral interstitial fluid in humans. Researcher: Roxana Aldea.

  3. Using novel nanoparticles produced in-house, with funding from BBSRC project grant we have investigated the capacity of the perivascular drainage pathways and demonstrated that particles of 20nm-1micrometre cannot drain along the intramural perivascular drainage pathways, suggesting these pathways are limited to the elimination of fluid and not cells.

  4. With funding from Biogen, we are currently defining the fine anatomical pathways for the communication between cerebrospinal fluid and the cerebral parenchyma. Researcher: Nazira Albargothy.

  5. Through a BBSRC CASE studentship in partnership with Kirkstall Ltd, we are creating an in vitro model of perivascular drainage pathways. Researcher: Abby Keable.

  6. White matter abnormalities are a major side effect after immunization in Alzheimer’s disease. With quantitative and 3D Gatan electron microscopy we are investigating the anatomical features of the arteries in white matter compared to arteries in the gray matter of the human brain. Researcher: Matthew MacGregor Sharp.

  7. The meninges are the interface between cerebrospinal fluid and interstitial fluid, with controversy regarding their permeability. Through a partnership with molecular microbiologists (Prof Myron Christodoulides) we are investigating the exact properties of the leptomeninges with particular emphasis on their selective permeability. This is relevant for a) the transfer of Aβ from the parenchyma to the CSF where it is measured as a biomarker for disease progression and b) the pathology of complications of subarachnoid haemorrhage.

  8. Our proteomic analyses in humans (Dr Antigoni Manousopoulou and Dr Spiro Garbis) and experimental studies highlighted the potential for Clusterin and Tissue Inhibitor of Metalloproteinases to be facilitators of intramural perivascular clearance. Collaborative work with Prof John Fryer, Mayo Clinica, USA to test the potential for Clusterin as therapeutic agent for restoring IPAD.

  9. Collaborative studies with Prof Donna Wilcock, University of Kentucky demonstrate that a diet low in vitamin B results in changes in the walls of cerebral blood vessels and failure of IPAD.

  10. Through a collaboration with Prof Darek Gorecki, University of Portsmouth, we are exploring how dystrobrevin and Aquaporin 4 are involved in IPAD.

  11. Through collaboration with Dr Felino Cagampang, funded by Rosetrees Trust we are exploring how maternal high fat diet results in changes in IPAD, predisposing to Alzheimer’s disease.

 

Perivascular drainage and the Origin of Neuro-ophthalmological Disease
Figure 1
Soluble tracers drain along the basement membranes
Figure 2
CAA interferes with perivascular drainage
Figure 3
Immune complexes in the brain and perivascular drainage of solutes from the brain
Figure 4

Department(s)

Clinical and Experimental Sciences

Affiliate Department(s)

Clinical Neuroscience Research group

Research project(s)

The Role of Arterial Pulsations in Perivascular Drainage and its Implications for Alzheimer's Disease

Perivascular drainage is an important process for the elimination of metabolic solutes from the brain. The failure of this process has important medical implications and the subsequent accumulation of the protein Aβ leads to the development of Alzheimer's Disease (AD). This project aims at resolving the driving forces for perivascular drainage via modelling techniques in order to inspire novel medication that might help reduce the impact of AD.

Investigating mitochondrial-derived vesicles and their relationship to Parkinson's disease pathology

 

Fellow of the Higher Education Academy. Chair of the Steering Committee for Women in Science, Engineering and Technology in the University of Southampton, Visiting Knowledge Exchange Fellow, University of Winchester, Home Office Licensed Teacher of Anatomy. Honorary Consul for Romania. Member of: PRIME- International Medical Education, British Pathological Society, Association for the Study of Medical Education, British Neuroscience Association, British Neuropathological Society, Federation of European Neuroscience Societies, International Brain Research Organisation, British Association of Clinical Anatomists, Anatomical Society, International Alzheimer’s Disease Forum, Association for the Study of Medical Education. Member of the Scientific Committee for Cerebral Amyloid Angiopathy 2014. Member of Scientific Committee for Vas-Cog 2015. Invited member of Cerebral Autoregulation Research Network. Associate Editor Frontiers in Ageing Neuroscience; Fluids and Barriers in the CNS, Romanian Medical Journal. Reviewer for Acta Neuropathologica, Neuropathology and Applied Neurobiology, Clinical Anatomy, Experimental Neurology, Alzheimer’s Society, Alzheimer’s Research UK, EU Commission, Brain Canada. Member of British Neuropathological Society Academic Committee; Organising Committee Alzheimer’s Disease International 2016, Member of Pool of Experts BBSRC, Committee Member for the USA National Plan to address Alzheimer’s disease, NIH, 2016.

 Prizes: Best research images at the 2011 Transmission Electron Microscopy British Society meeting; Vice-Chancellor Award for Best Teacher, University of Southampton, 2013; Best poster (senior author) Alzheimer’s Research UK 2014, 3rd prize poster Glia Magdeburg (Germany), 2014. Staff Achievement Award, University of Southampton 2014; best oral presentation British Association of Clinical Anatomists, 2015; Dementia Leader Award, Alzheimer’s Society 2015.

 

 

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Anatomy teaching (lead in Semester 3 BM4 and teacher in Semester 4 BM4), Module Lead Year 3 Scientific Basis Of Medicine). Marker Intermediate and Finals Examinations. Programme Lead for the Masters in Medical Sciences, Faculty of Medicine, University of Southampton, 2010-2016. External Examiner, School of Medicine, University of Sheffield. External Examiner Queen Mary University of London. Supervisor/co-supervisor for 4PhD students, 1MSc, 7 MMedSc, 6BSc, 38 BM5 project students. Advisor for PhD Students in Binghamton University, USA, University of Zurich, Switzerland. 

Professor Roxana O Carare
LD 66 Clinical Neurosciences Southampton General Hospital South Academic Block Level D MP806

Room Number: SGH/LD80A/MP806

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