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Medicine

Dr Roxana Octavia Carare MD, PhD

Associate Professor Clinical Anatomy, Programme Lead MMedSc, Equality and Diversity Lead

Dr Roxana Octavia Carare's photo
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Roxana Carare is a medically qualified Associate Professor in anatomy 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

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

Roxana Carare is a medically qualified Associate Professor in cerebrovascular ageing 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. Her main international recognition has come from the neuroanatomy and neuropathology research she leads, demonstrating the unique pathways by which fluid and soluble amyloid are eliminated from the brain along basement membranes within the walls of cerebral capillaries and arteries. The focus of her research is to manipulate the pathways to improve the clearance of amyloid and interstitial fluid from the ageing brain, preventing neurodegenerative diseases. Interdisciplinary work led by Roxana has been published in high impact peer review journals and Encyclopaedia of Neuroscience. Roxana teaches clinical anatomy to undergraduate and post-graduate medical and health-care professionals and leads the undergraduate Masters in Medical Sciences Programme. Through her senior role within the University-Industry Sector Team, Roxana actively engages with industrial partners. Promoting equality and diversity locally and internationally is an important priority for Roxana. She is part of the International Scientific Steering Committee of Vas-Cog, Cerebral Amyloid Angiopathy, Alzheimer’s Society Romania. Roxana is a reviewer for neuroscience, neuropathology and Alzheimer’s disease journals, for national and international funding agencies, as well as for the European Commission. Of Romanian heritage, Roxana is Honorary Consul of Romania, Advisor for Age UK Southampton and Patron of Libra Foundation.

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-present

Research

Responsibilities

Publications

Teaching

Contact

Research interests

The major aims of the research led by Dr Carare are:

{1] To determine why elimination of Amyloid-β (Aβ) from the brain fails with age and Alzheimer’s disease (AD)

{2] To translate the basic science in [1} above into therapies that facilitate the elimination of Aβ for the prevention and treatment of AD

Perivascular elimination of soluble Aβ from the brain

Dr Carare has demonstrated a new pathway for the elimination of solutes from the brain, along the basement membranes of capillaries and arteries (Fig 2). This pathway is now recognised as a very significant route for the clearance of Aβ from the brain. Failure of perivascular drainage of Aβ as cerebral arteries age appears to be an important factor in the aetiology of Alzheimer’s disease. With advancing age and in Alzheimer’s disease, elimination of Aβ fails and is deposited within basement membranes further impeding the elimination of Aβ and other solutes from the brain (Fig 3). In addition to age, possession of the ApoE4 genotype and high levels of cholesterol in the blood are major risk factors for Alzheimer’s disease. The working hypothesis for the projects led by Dr Carare is that these risk factors impede elimination of Aβ and other soluble metabolites from the brain and ultimately, result in loss of homeostasis of the neuronal environment, neuronal dysfunction and cognitive decline.

Age and hypercholesterolaemia: risk factors for Alzheimer’s Disease

Using methods that range from in vivo techniques, to surface plasmon resonance (BIAcore) and atomic force microscopy, in collaboration with colleagues across the University of Southampton, the aim of this project is to characterize in detail the interactions between Aβ, components of basement membranes and lipidated isoforms of ApoE, in order to intervene therapeutically with a chaperone molecule that could facilitate the interactions and clearance of Aβ. This project also employs proteomics and lipidomics to study the changes that occur in human basement membranes with age and hypercholesterolaemia.

Neuroimmunology

Having shown that solutes drain from brain tissue along the narrow basement membranes in the walls of cerebral capillaries and arteries Dr Carare developed the quantitative methodology to test systems by which such drainage is impaired. She demonstrated that when immune complexes formed in the brain, they also formed in the perivascular drainage pathways and hindered the elimination of solutes from the brain (Fig 4). The significance of this area of work is that is forms the basis for resolving the current failure of immunotherapy for human AD in which insoluble Aβ is cleared from the brain but not from the perivascular drainage pathways.

Anatomy

1. Dr Carare is demonstrating the anatomical pathway by which solutes are cleared from cerebrovascular basement membranes to cervical lymph nodes in humans. Human cadaveric studies are used to demonstrate the presence of lymph nodes at the base of the skull, in direct relationship with the internal carotid and vertebral arteries. The aim is to describe the communication between the pathway for the drainage of interstitial fluid from the brain along the walls of cerebral arteries with the lymphatic system, widening the applications of the perivascular drainage pathway to the pathogenesis of CNS immune disorders.

2. Using mathematical models and medical imaging, Dr Carare is testing the hypothesis that the morphology and pattern of branching of the arterial tree are key factors in the risk of developing cerebral amyloid angiopathy. The objective is to develop a radiological biomarker for early detection of Alzheimer’s disease.

3. Study the permeability of the leptomeninges, with relevance to testing how biomarkers reach the CSF.

4. Test the hypothesis that the subarachnoid space continues alongside the olfactory nerves through cribriform plate into  the nasal mucosa, with relevance to transmission of pathogens into the CSF and neuroimmunology.

5. Analyse the roles of pericytes in clearance of interstitial fluid of the brain.

Community studies in the elderly

The results from laboratory experiments suggest a role for hypercholesterolaemia in the onset of dementia and Dr Carare aims to widen the spectrum of research to incorporate preventative measures such as diet and lifestyle, for facilitation of perivascular drainage of Aβ and toxic metabolites from the brain. Dr Carare maintains a proactive interest in the problems that occur in elderly medicine. She works on establishing the protective factors against depression and cognitive decline in the aged in the UK and Eastern Europe.

Research projects
  • Mar 2013-Mar 2015: Alzheimer’s Research UK: Changes in blood vessels in Alzheimer’s Disease.

Staff: Abby Keable (research assistant)

  • March 2012-April 2013: The GB Sasakawa Foundation. Establishing a new collaboration with Kyoto University.
  • Oct 2012-Sept 2015. Age UK. Defining the failure of elimination of Aβ from the brain in the search for a robust therapy for Alzheimer's Disease.

PhD student: Alan Morris

Staff employed on this project:
Maureen Gatherer (senior technician)
Antigoni Manousopoulou (proteomics research assistant)
Matthew MacGregor Sharp (electron microscopist)
Rute Fernandes (nanoparticle specialist)
Subhojit Chakraborty (post-doctoral specialist in two-photon microscopy)


• Mar 2013-Mar 2016: Rosetrees Trust: Biochemical changes in cerebral amyloid angiopathy.
• Aug 2013-Aug 2014: Kirby Laing Foundation: Epigenetic changes in offspring of maternal high fat.
• Apr 2014-Apr 2015: Protea Biosciences: Biomolecular imaging in offspring of maternal high fat.
• Sept 2014-Aug 2017: Biogen Ltd. Defining the connections between the subarachnoid space and the brain parenchyma.
• Aug 2014: Equipment grant: SP8 Confocal. Alzheimer’s Research UK.

PhD supervision

Roxana has supervised over 30 BMedSc students, 2 MMedSc students, 1MSc, all completing during the minimum allocated time.

Musab Sahrim (co-supervised with Prof Mark Nixon). Title: Arterial branching patterns: new radiological biomarker for Alzheimer’s disease? Funded by Government of Malaysia

Alexandra Diem (co-supervised with Prof Neil Bressloff).Title: A computational model for the motive force for the perivascular clearance of solutes from the brain. Funded by EPSRC-Complexity Science

Alan Morris (co-supervised with Dr C. Hawkes, Prof J Nicoll)Title: Defining the exact route for the perivascular clearance of amyloid beta and apolipoproteins. Funded by Age UK.

Roxana Aldea (co-supervised with Dr G. Richardson). Title: The role of cerebral smooth muscle cells in the perivascular clearance of amyloid-beta. Funded by EPSRC-Complexity Science.

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

Academic unit(s)

Clinical and Experimental Sciences Academic Units

Affiliate academic unit(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.

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, Year 3 SBOM). Marker Intermediate and Finals Examinations. Programme Lead for the Masters in Medical Sciences, Faculty of Medicine, University of Southampton, since 2010. External Examiner, School of Medicine, University of Sheffield. Supervisor/co-supervisor for 4PhD students, 1MSc, 2 MMedSc, 6BSc, 30BM5 project students. Advisor for PhD Students in Binghamton University, USA, University of Zurich, Switzerland. 

Summer School co-organiser and teacher British Neuropathological Society 2015.
Supervisor for visiting students from Otto-von-Guericke University, Magdeburg and University of Kyoto.

Dr Roxana Octavia Carare
LD 66 Clinical Neurosciences Southampton General Hospital South Academic Block Level D MP806

Room Number: SGH/LD80A/MP806

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