Approximately 150,000 people in the UK suffer a stroke every year, due either to a blocked blood vessel (causing ischaemic stroke), or a burst blood vessel (which causes haemorrhagic stroke). Apart from stroke unit care, treatments are limited and many patients either die or are left disabled and dependent on others.
Our clinical research focuses on the management of acute stroke (blood pressure lowering, tranexamic acid for intracerebral haemorrhage), acute prevention of recurrence (intensive antiplatelets), enhancing recovery (stem cell mobilisation), and prevention of cognitive decline (intensive blood pressure and/or lipid lowering).
Our laboratory studies investigate the blood brain barrier and how its integrity may be maintained after a stroke.
What we are doing in...
1. Clinical studies
The Nottingham Stroke Trials Unit runs a number of large multi-centre phase 3 clinical trials, both in the UK and Internationally. In addition, we also run a number of smaller phase II clinical trials, as well as performing systematic reviews and meta-analysis. (List of clinical stroke trials.)
- Phase I trials in volunteers
- Phase II and phase III trials in acute stroke, stroke recovery and stroke prevention
- Meta-analysis using both summary and individual patient data
- Data (safety) monitoring committees
- Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS)
- A randomised controlled trial of Tranexamic acid in Intracerebral Haemorrhage 2 (TICH-2)
- Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial (RIGHT-2)
- UK Co-ordinators EuroHYP-1 - A European, multicentre, randomised, phase III, clinical trial of hypothermia plus medical treatment versus best medical treatment alone for acute ischaemic stroke
2. Systematic reviews
- Acute interventions
- Secondary prevention
- Recovery and rehabilitation
3. Translational studies
Our translational studies focus on the elucidation of the mechanisms that may account for the breakdown and recovery of the blood-brain barrier (BBB) with an aim to discover novel therapeutic mediators that can effectively prevent or reverse the formation of brain oedema, the main cause of death within the first week after an ischaemic stroke.
Translational stroke studies
- Brain oedema: small GTP-binding protein RhoA and its downstream effectors; ROCK, MLC
- Hyperglycaemia-evoked BBB dysfunction: protein kinase C family and its specific isoforms
- Ischaemic injury and BBB integrity: matrix metalloproteases (MMP-2, MMP-9)
- BBB pathophysiology: plasminogen-plasmin system components; uPA, uPAR, tPA and PA-1
- Neuroinflammation: cytokines and chemokines
- Therapeutic role of hypothermia: cytokines, cytoskeleton and tight junctional complexes
- Oxidative stress and BBB breakdown: free radicals, NO, NOSs, SODs, catalase, GPx
- Clinical biomarkers: for effective diagnosis and differentiation of stroke subtypes
Our research impact is reflected in the following:
Publications in leading journals e.g. Stroke, Lancet, New Eng Journal
- Shao B, Srivastava K, Bayraktutan U. PKC-β exacerbates in vitro brain barrier damage in hyperglycemic settings via regulation of RhoA/Rho-kinase/MLC2 pathway. J Cereb Blood Flow Metabol 2013
- Sacco RL, Diener HC, Yusuf S, Cotton D, Ounpuu S, Lawton WA, Palesch Y, Martin RH, Albers GW, Bath P, Bornstein N, Chan BP, Chen ST, Cunha L, Dahlof B, De Keyser J, Donnan GA, Estol C, Gorelick P, Gu V, Hermansson K, Hilbrich L, Kaste M, Lu C, Machnig T, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, Vandermaelen C, Voigt T, Weber M, Yoon BW; the PRoFESS Study Group. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent strokes. NEJM 2008;359(12):1238-51
- Bath PM, Lees KR, Schellinger PD, Altman H, Bland M, Hogg C, Howard G, Saver JL; European Stroke Organisation Outcomes Working Group. Statistical analysis of the primary outcome in acute stroke trials. Stroke 2012;43:1171-8. Epub 15 March 2012
See details of more publications under individual researchers' profiles.
Safety and Efficacy of Triple Antiplatelets for reducing dependency after Ischaemic Stroke; The TARDIS randomised controlled trial.
Tranexamic acid for hyperacute primary Intracerebral Haemorrhage (TICH-2).
Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2): Assessment of safety and efficacy of transdermal glyceryl trinitrate, a nitric oxide donor, and of the feasibility of a multicentre ambulance-based stroke trial.
DMT-EPC Endothelial progenitor cells: potential biomarkers for diagnosis and prognosis of ischaemic stroke.
See our other major awards from funders including the NIHR HTA and the Stroke Association.
NIHR Senior Investigator award
Professor Philip Bath, head of the Stroke Research group, has been named an NIHR Senior Investigator. Senior Investigators are the NIHR’s pre-eminent researchers and include some of the nation’s most outstanding leaders of clinical and applied health and social care research.
We maintain strong collaborative links with key groups both within the University of Nottingham and outside with colleagues in the UK, Europe and worldwide.