Lipidomic signature of stroke recurrence after transient ischemic attack.

CT scan of a brain after ischemic stroke.

Purroy F, Ois A, Jove M, Arque G, Sol J, Mauri-Capdevila G, Rodriguez-Campello A, Pamplona R, Portero M, and Roquer J. (2023) Lipidomic signature of stroke recurrence after transient ischemic attack. Scientific Reports

Strokes are caused by inadequate blood flow to the brain which limits oxygen supply and results in cell death. Strokes require immediate medical help to reduce brain damage, however they result in more than six million deaths a year globally and in those that receive help in time can still cause disability. Strokes can be split into two categories: hemorrhagic stroke caused by bleeding and ischemic strokes caused by a lack of blood flow from a blockage. A transient ischemic attack (TIA) falls under ischemic strokes but is characterized by a transient period of neurological deficits due to brain ischemia. People with TIA are at a greater risk of an ischemic stroke with stroke recurrence, especially in the three months following TIA, however this risk is not the same across all people who have experienced TIA. The risk level is associated with sex, presence of intracranial or extracranial stenosis, cardioembolism, diffusion weighted imaging abnormalities, repeated TIA, and motor weakness. Since medical attention is needed as fast as possible when a stroke is occurring, the identification of something that could inform the patient of their risk, such as a biomarker, would be invaluable. Previous work by the authors has determined that there may be an association between lipids and their metabolites and stroke risk. Here, Purroy et al performed lipidomic analyses on TIA patients that had consecutive TIA experiences to compare the lipidomic profile of those with stroke recurrence within the 90 days following TIA and those without the recurrence.

To perform this study, 460 consecutive TIA patients were included that had been to a stroke neurologist within the first 24 hours after onset of symptoms from January 2006 to January 2015. They were then followed up with after 90 days to assess whether they suffered stroke recurrence due to an ischemic cause. To explore the whole lipidome in the participants, an untargeted approach was employed. Small changes were seen in the lipidome when there was a stroke recurrence compared to when there was not and they found that 7 of 152 lipids were expressed differently, all downregulated, between the two groups. These seven included five triacylglycerides, one diacylglyceride, and one ethanolamine plasmalogen. Interestingly, of the 37 individuals that experienced the stroke recurrence 23 were female and the stroke recurrence group also had a higher proportion of previous ischemic stroke, duration of symptoms for more than 10 minutes, and motor impairment.

Purroy et al were interested in determining if there are differences in the lipidome between people who have experienced TIA that also suffer from stroke recurrence in the following 90 days and those that do not. Lipidome differences were found between these two groups of patients and were very specific, consisting of seven lipids. Due to this specificity, the authors suggest that the metabolic pathways and mechanisms that involve these lipids could be important to the pathology of stroke recurrence. Interestingly, the lipids that were found to be different have roles in bioenergetics (triacylglycerols), in membrane structure (plasmalogens and diacylglycerols), are an important antioxidant in the brain (plasmalogens), or have roles in membrane structure and vesicular fusion (plasmalogens). The low level of these lipids in people who suffered stroke recurrence supports the theory that these changes to the lipidome have physiopathological roles. As well, if these changes are shown to consistently be significantly different with stroke recurrence following TIA, this could be a biomarker for an increased risk of ischemic stroke.