NACCSGBI Project Grant

The successful applicant for the NACCSGBI Research Grant was:

Principle Applicant
Dr Martyn Ezra
University of Oxford

Determining the role of Nitric Oxide Depletion in Early Brain Injury after Subarachnoid Haemorrhage using Multimodal Magnetic Resonance Imaging


Scientific Abstract

Subarachnoid Haemorrhage (SAH) is a devastating subset of stroke, characterised by high patient mortality and long-term disability. One of the major determinants of morbidity is a global cerebral injury that develops in the first 72 hours following SAH, known as Early Brain Injury (EBI). The mechanisms of EBI are poorly understood, but animal studies suggest that cellular dysfunction induced by ischemic injury is exacerbated by nitric oxide (NO) depletion.

1) Use multimodal MRI techniques to determine the extent of neurovascular-astrocyte dysfunction during EBI in high grade SAH in humans.
2) Quantify the role of the NO signalling pathway in the pathogenesis of EBI, through pharmacological manipulation of NO levels using an exogenous NO donor.

40 high-grade SAH patients in the first 72 hours after aneurysmal rupture will undergo multimodal MRI followed by randomised administration of an exogenous NO (sodium nitrite) or saline control and repeat imaging.

Through direct pharmacological manipulation of NO levels in vivo, we will examine the role of NO in neuroprotection and build upon animal evidence suggesting that NO depletion plays a critical role in EBI. These findings will help inform future early phase clinical studies into NO replacement and treatment of EBI.