Stroke is a devastating neurological disorder that is characterized by the sudden disruption of blood flow to the brain. Lipids are essential components of brain structure and function and play pivotal roles in stroke pathophysiology. Dysregulation of lipid signaling pathways modulates key cellular processes such as apoptosis, inflammation, and oxidative stress, exacerbating ischemic brain injury. In the present review, we summarize the roles of lipids in stroke pathology in different models (cell cultures, animal, and human studies). Additionally, the potential of lipids, especially polyunsaturated fatty acids, to promote neuroprotection and their use as biomarkers in stroke are discussed.

Docosahexaenoic acid-containing lysophosphatidylcholine (DHA-LysoPC) is presented as the main transporter of DHA from blood plasma to the brain. This is related to the major facilitator superfamily domain-containing protein 2A (Mfsd2a) symporter expression in the blood–brain barrier that recognizes the various lyso-phospholipids that have choline in their polar head. In order to stabilize the DHA moiety at the sn-2 position of LysoPC, the sn-1 position was esterified by the shortest acetyl chain, creating the structural phospholipid 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC). This small structure modification allows the maintaining of the preferential brain uptake of DHA over non-esterified DHA. Additional properties were found for AceDoPC, such as antioxidant properties, especially due to the aspirin-like acetyl moiety, as well as the capacity to generate acetylcholine in response to the phospholipase D cleavage of the polar head. Esterification of DHA within DHA-LysoPC or AceDoPC could elicit more potent neuroprotective effects against neurological diseases.

Albeit the molecular mechanisms of gene expression are well documented, our understanding of their dynamics is much less advanced. Recent experimental evidence has revealed that gene expression might be accurately organized in space, with several molecular actors localized to specific positions in the cell. However, the influence of this spatial localization on the dynamics of gene expression is unclear. This issue is also central in synthetic biology, where one usually considers the spatial localization in the cell of the genes of the inserted synthetic construct as irrelevant for its temporal dynamics. Here, we assessed the influence of the spatial distribution of the genes on the dynamics of 3-gene transcriptional ring networks regulated by repression, i.e. repressilator circuits, using individual-based modelling to simulate their dynamics in two and three space dimensions. Our simulations suggest that variations of spatial parameters - namely the degree of demixing of the positions of the gene or the spatial range of the mRNA and proteins (i.e. the typical distance they travel before degradation) - have dramatic effects by switching the dynamical regime from spontaneous oscillations to a stationary state where each species fluctuates around a constant value. By analogy with the bifurcations arising from the variation of kinetic parameters, we referred to those transitions as space-induced bifurcations. Taken together, our results strongly support the idea that the spatial organization of the molecular actors of transcriptional networks is crucial for the dynamics of gene expression and suggest that the spatial localization of the synthetic genes in the cell could be used as an additional toggle to control the dynamics of the inserted construct in synthetic biology experiments.