Lin Kooi Ong, PhD
In my previous Blogging Stroke post, it is apparent that brain damage is not only confined to the primary infarction site after ischemic stroke, but also in remote regions of the brain. Indeed, secondary thalamic degeneration has been constantly observed in neuroimaging studies among stroke patients with cortical stroke as well as in experimental stroke models. While the mechanisms involved in the development of secondary thalamic degeneration have not been fully elucidated, studies suggest that neuroinflammation is most likely involved. Microglia are thought to be the primary resident immune cells of the brain mediating neuroinflammatory responses after stroke.
In this study, Cao and colleagues investigated the spatiotemporal changes of neurodegeneration, neuroinflammatory responses, and microglial activation for up to 84 days after experimental cortical stroke. They found that microglial activation occurred rapidly and preceded the progressive neuronal loss in the thalamus after stroke. Results from transcriptome analysis of the thalamus showed robust increase in the expression of neuroinflammation and microglia related genes. Excitingly, using a cell sorting technique, the team discovered a unique subtype of CD11c-positive microglia with disease-associated molecular profiles in the thalamus. These disease-associated microglia include reduced expression of Tmem119 and CX3CR1, and increased expression of ApoE, Axl, LpL, CSF1, and Cst7.
The findings from this study, along with emerging evidence,1 suggest that microglia are a key mediator in the progression of secondary thalamic degeneration after stroke. It is noteworthy to mention that a recent study by Kluge and colleagues identified microglia during secondary thalamic degeneration lose their ability to direct process extension toward local injury, but show an increase in the phagocytic function particularly in the late phase after experimental cortical stroke.2 Following stroke, chronic microglial activation is detrimental and has been associated with persistent thalamic neuronal loss and several late phase functional disturbances. The distinct microglial phenotypes and responses in the thalamus provide potential therapeutic targets to limit secondary neurodegeneration after stroke. Further, the delayed nature of secondary thalamic degeneration offers an extended therapeutic time window.
1. Cao Z, Harvey SS, Bliss TM, Cheng MY, Steinberg GK. Inflammatory responses in the secondary thalamic injury after cortical ischemic stroke. Front Neurol. 2020;11:236.
2. Kluge MG, Abdolhoseini M, Zalewska K, Ong LK, Johnson SJ, Nilsson M, et al. Spatiotemporal analysis of impaired microglia process movement at sites of secondary neurodegeneration post-stroke. J Cereb Blood Flow Metab. 2019;39:2456-2470.