2019 ABN Robin Brown

Dr Robin Brown

2019 ABN Fellowship

Blood brain barrier permeability in cerebral small vessel disease

Cerebral small vessel disease (SVD) is an enormous public health problem; it represents 20% of ischaemic strokes and is the most common cause of vascular dementia. Understanding of the pathophysiology is nevertheless incomplete and there are no disease-modifying treatments.

Two related novel pathophysiological mechanisms have recently been proposed, namely that inflammation and increased permeability of the blood-brain barrier (BBB) are implicated in the development of SVD. This might mediate the progression from areas of haemodynamic disturbance to the white matter damage seen in the disease.

Cross-sectional MRI studies have shown increased BBB permeability in SVD, and pilot data from Cambridge using positron emission tomography (PET) has shown glial activation (evidence of neuroinflammation) in patients. The key question of whether these processes are causal or merely secondary phenomenon remains uncertain. I will aim to provide further insight into the roles of these process taking blood and CSF samples from patients with SVD and healthy controls who are undergoing combined PET/MRI imaging. I will measure inflammatory markers and the CSF/serum albumin ratio which is the gold standard of quantifying in vivo BBB permeability and examine its relationship with radiological markers of SVD.

This will be complemented by analysis of longitudinal data to determine whether regions of BBB permeability and neuroinflammation progress to tissue damage, as assessed by diffusion tensor imaging (DTI) parameters which are the most sensitive markers of white matter structural damage. These results will build on existing knowledge of the pathophysiology of SVD and potentially inform future options for therapeutic intervention.


How often does white matter hyperintensity volume regress in cerebral small vessel disease?

Brown RB, Tozer DJ, Egle M, Tuladhar AM, de Leeuw FE, Markus HS

International Journal of Stroke 2023 Oct;18(8):937-947. doi: 10.1177/17474930231169132.


Do regions of increased inflammation progress to new white matter hyperintensities? A longitudinal positron emission tomography-magnetic resonance imaging study

Tozer DJ, Brown RB et al.

Stroke. 2023;54:549–557


MINocyclinE to Reduce inflammation and blood brain barrier leakage in small Vessel diseAse (MINERVA) trial study protocol

Brown RB et al.

Eur Stroke J 2022; 7(3):323-330


Prevalence of, and risk factors for, cognitive impairment in lacunar stroke

Ohlmeier L, Nannoni S, Pallucca C, Brown RB et al.

International Journal of Stroke 2022; 18(1):62-69


Cognitive impact of cerebral microbleeds in patients with symptomatic small vessel disease

Nannoni S, Ohlmeier L, Brown RB et al

International Journal of Stroke 2022; 17(4):415-424


Individual markers of cerebral small vessel disease and domain-specific quality of life deficits

Fernando J, Brown RB et al.

Brain and Behavior 2021 May;11(5):e02106. doi: 10.1002/brb3.2106.


Rate of, and risk factors for, white matter hyperintensity growth: a systematic review and meta-analysis with implications for clinical trial design

Brown RB, Low A, Markus HS

JNNP 2021; 92:1271-1277


Do cerebral small vessel disease and multiple sclerosis share common mechanisms of white matter injury? A genetic study

Brown RB et al

Stroke 2019; 50(8):1968-1972