Dr. Rufus Akinyemi, Consultant Neurologist, FMC Abeokuta reports on a2010 IBRO Research Fellowship at the Institute for Ageing and Health, Newcastle University, United Kingdom

Stroke is a leading non-communicable disease all over the world, and current reports suggest that it is  assuming epidemic proportions in middle and low- income countries. About 30% of stroke survivors ultimately develop vascular dementia even though the exact mechanisms are yet poorly understood. Moreover, much of what is known about the epidemiology, natural history and neurobiology of post-stroke cognitive dysfunction have had little contribution from sub-Saharan Africa.
With this background and my training in clinical neurology as well as being a witness of the evolving epidemiology of stroke and its short- and long term consequences  in sub-Saharan Africa, I  took up the prestigious IBRO Research Fellowship under the tutelage of Prof Raj Kalaria,Deputy Director of the MRC Newcastle Centre for Brain Ageing and Vitality at the Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.
My work, in the course of the fellowship, involved a stinct in the Acute Stroke Unit of the Royal Victoria Infirmary (RVI), Newcastle upon Tyne, UK (Figure 1) as well as laboratory research centred on investigating the cellular and molecular mechanisms of cerebral injury and cognitive impairment after stroke (Figure 2).

Figure 2. Dr. Rufus Akinyemi in the Neurovascular Research Laboratory of the Institute for Ageing and Health, Newcastle upon Tyne, UK.

Under the guidance of Prof Gary Ford, Director of the UK Stroke Research Network and a leading stroke physician based in the Stroke Centre of the RVI, the stinct in the Acute Stroke Unit exposed me to the state-of-the-art and cutting edge stroke medicine as practised in the centre. The timely triaging, rapid assessment, neuroimaging and thrombolytic intervention (when necessary) of cases of acute stroke were exciting, and the multidisciplinary approach to care including regular MDT meetings, post –discharge care, networking with community- based care providers and excellent patient follow ups provided an excellent model worthy of adaptation to  a developing country setting. I also took time off, as much as time permitted, to attend the weekly educational programmes of the Department of Neurology of the RVI.

Figure1. Dr. Rufus Akinyemi participating in the Stroke  Multidisciplinary Team (MDT) Meeting of the Acute Stroke Unit of the Royal Victoria Infirmary (RVI), Newcastle upon Tyne, UK.

For the laboratory-based programme, we obtained human brain tissue  from the Newcastle Brain Tissue Resource (NBTR) brain bank, including brain tissue that have accrued from the  MRC (UK)- funded research programme on Cognitive Functions After Stroke (COGFAST)  based in the Institute for Ageing and Health of the Newcastle University. We  used markers of neurodegenerative pathology (amyloid, soluble amyloid oligomers and tau)  and synaptic density (synaptophysin, drebrin and vesicular glutamate transporter), and the techniques of immunocytochemistry, in-vitro imaging and computer-based analysis with the Image Pro Plus software to investigate brain tissue sections obtained from the hippocampus and entorhinal cortex of  the post-stroke cohort in comparison with normal controls, vascular dementia (VaD), Alzheimer’s disease (AD) and mixed AD/VaD.
The results showed increased accumulation of amyloid but relatively similar level of tau in post-stroke brains compared to normal controls, and much less than the amount of amyloid and tau quantified from the AD and mixed AD/ VaD brain tissue. In addition, we surprisingly found a higher level of amyloid (but relatively similar levels of tau) in non-demented than in demented post-stroke brains. We, however, found a significantly higher amount of drebrin, a post-synaptic marker, in the non-demented than in the demented post-stroke brains. This correlated with an earlier finding from the group of an higher volume of hippocampal CA1 sub-regional neurons in the non-demented compared to the demented post-stroke brains. Vascular pathologies were however similar between the non-demented and demented post-stroke groups.
These results suggest that hippocampal neurodegenerative and vascular pathologies interact with synaptic densities, neuronal volumes (and possibly other yet to be identified variables) to determine the cognitive trajectory after stroke, and that higher hippocampal synaptic density and neuronal volumes (possibly signatures of higher cognitive reserve) may protect against or delay the onset of dementia after stroke.
During the research fellowship, I also spearheaded the setting up of a parallel Nigerian longitudinal study to investigate the profile, determinants and outcome of cognitive dysfunction in Nigerian stroke survivors in collaboration with the established Newcastle COGFAST Project. The pilot study revealed cognitive dysfunction in 28% of 42 stroke survivors while the main study is currently in progress.
In addition, the fellowship period afforded me the opportunity of effective networking and contribution to the growth of African Neuroscience. The IBRO Alumni – Nigeria group was inaugurated to network and coordinate young Nigerian neuroscientists who have participated in IBRO programmes. I also served as editor, and contributed two review articles to an IBRO-sponsored special Neuroscience Edition of a growing African journal – Archives of Ibadan Medicine.
In all, the fellowship period was a great leap in my development and progress as a Neurophysician – scientist, and I look forward to making significant contributions to Neuroscience research, education and research capacity building in Africa and beyond in the years ahead.
The fellowship programme has enhanced the international image of the Federal Medical Centre Abeokuta and further strengthened the growing relationship between the centre and experts based in the Newcastle University, UK. An immediate outcome of this was a visit to the FMC Abeokuta by my UK host and mentor, Prof Rajesh Kalaria in December 2011. Some of the researches arising from the programme have been presented in international scientific conferences in the UK, France and Ethiopia while a number of publications are in preparation. The research exposure of this programme has also inspired me to spearhead the promotion of research culture in our centre through the recent inauguration of the FMC Abeokuta Research Forum. My colleagues and trainee postgraduate doctors in the Department of Internal Medicine have been positively influenced in the pursuit of clinical excellence and research mindedness.

Acknowledgments

• The Medical Director and Management, Federal Medical Centre Abeokuta, Nigeria.
• International Brain Research Organization (IBRO), Paris, France.
• Institute for Ageing and Health, Newcastle University, UK.
• Prof. Rajesh N. Kalaria – Professor of Cerebrovascular Neuropathology and Deputy Director of the MRC  Newcastle Centre for Brain Ageing and Vitality, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom
• Prof. Adesola Ogunniyi- Professor of Neurology, University of Ibadan/University College Hospital, Ibadan, Nigeria.
• The Neurovascular Research Group, Institute for Ageing and Health, Newcastle University, UK.
• The COGFAST- Newcastle Project Team
• The  COGFAST- Nigeria Study Team
• My family and friends.

Dr. Rufus  Akinyemi
Division of Neurology, Department of Medicine
Federal Medical Centre, Abeokuta, NIGERIA.
rufusakinyemi@yahoo.com,  mobile no: +234 803 3704 384