Dataset Information

Perioperative stroke deteriorates white matter integrity by enhancing cytotoxic CD8⁺ T-cell activation.

ABSTRACT:

Aim

To explore the regulatory mechanisms of microglia-mediated cytotoxic CD8⁺ T-cell infiltration in the white matter injury of perioperative stroke (PIS).

Methods

Adult male C57BL/6 mice were subjected to ileocolic bowel resection (ICR) 24 h prior to permanent distant middle cerebral artery occlusion (dMCAO) to establish model PIS. White matter injury, functional outcomes, peripheral immune cell infiltration, and microglia phenotype were assessed up to 28 days after dMCAO using behavioral phenotyping, immunofluorescence staining, transmission electron microscopy, western blot, and FACS analysis.

Results

We found surgery aggravated white matter injury and deteriorated sensorimotor deficits up to 28 days following PIS. The PIS mice exhibited significantly increased activation of peripheral and central CD8⁺ T cells, while significantly reduced numbers of mature oligodendrocytes compared to IS mice. Neutralizing CD8⁺ T cells partly reversed the aggravated demyelination following PIS. Pharmacological blockage or genetic deletion of receptor-interacting protein kinase 1 (RIPK1) activity could alleviate CD8⁺ T-cell infiltration and demyelination in PIS mice.

Conclusion

Surgery exacerbates demyelination and worsens neurological function by promoting infiltration of CD8⁺ T cells and microglia necroptosis, suggesting that modulating interactions of CD8⁺ T cells and microglia could be a novel therapeutic target of long-term neurological deficits of PIS.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC11227991 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Perioperative stroke deteriorates white matter integrity by enhancing cytotoxic CD8<sup>+</sup> T-cell activation.

Zhou Yuxi Y Wang Xin X Yin Wen W Li Yan Y Guo Yunlu Y Chen Chen C Boltze Johannes J Liesz Arthur A Sparwasser Tim T Wen Daxiang D Yu Weifeng W Li Peiying P

CNS neuroscience & therapeutics 20240701 7

<h4>Aim</h4>To explore the regulatory mechanisms of microglia-mediated cytotoxic CD8<sup>+</sup> T-cell infiltration in the white matter injury of perioperative stroke (PIS).<h4>Methods</h4>Adult male C57BL/6 mice were subjected to ileocolic bowel resection (ICR) 24 h prior to permanent distant middle cerebral artery occlusion (dMCAO) to establish model PIS. White matter injury, functional outcomes, peripheral immune cell infiltration, and microglia phenotype were assessed up to 28 days after dM ...[more]

PMID: 38973085

Similar Datasets

Project description:Frontoparietal white matter supports information transfer between brain areas involved in complex haptic tasks such as somatosensory discrimination. The purpose of this study was to gain an understanding of the relationship between microstructural integrity of frontoparietal network white matter and haptic performance in persons with chronic stroke and to compare frontoparietal network integrity in participants with stroke and age matched control participants. Nineteen individuals with stroke and 16 controls participated. Haptic performance was quantified using the Hand Active Sensation Test (HASTe), an 18-item match-to-sample test of weight and texture discrimination. Three tesla MRI was used to obtain diffusion-weighted and high-resolution anatomical images of the whole brain. Probabilistic tractography was used to define 10 frontoparietal tracts total; Four intrahemispheric tracts measured bilaterally 1) thalamus to primary somatosensory cortex (T-S1), 2) thalamus to primary motor cortex (T-M1), 3) primary to secondary somatosensory cortex (S1 to SII) and 4) primary somatosensory cortex to middle frontal gyrus (S1 to MFG) and, 2 interhemispheric tracts; S1-S1 and precuneus interhemispheric. A control tract outside the network, the cuneus interhemispheric tract, was also examined. The diffusion metrics fractional anisotropy (FA), mean diffusivity (MD), axial (AD) and radial diffusivity (RD) were quantified for each tract. Diminished FA and elevated MD values are associated with poorer white matter integrity in chronic stroke. Nine of 10 tracts quantified in the frontoparietal network had diminished structural integrity poststroke compared to the controls. The precuneus interhemispheric tract was not significantly different between groups. Principle component analysis across all frontoparietal white matter tract MD values indicated a single factor explained 47% and 57% of the variance in tract mean diffusivity in stroke and control groups respectively. Age strongly correlated with the shared variance across tracts in the control, but not in the poststroke participants. A moderate to good relationship was found between ipsilesional T-M1 MD and affected hand HASTe score (r = - 0.62, p = 0.006) and less affected hand HASTe score (r = - 0.53, p = 0.022). Regression analysis revealed approximately 90% of the variance in affected hand HASTe score was predicted by the white matter integrity in the frontoparietal network (as indexed by MD) in poststroke participants while 87% of the variance in HASTe score was predicted in control participants. This study demonstrates the importance of frontoparietal white matter in mediating haptic performance and specifically identifies that T-M1 and precuneus interhemispheric tracts may be appropriate targets for piloting rehabilitation interventions, such as noninvasive brain stimulation, when the goal is to improve poststroke haptic performance.

Dataset Information

Perioperative stroke deteriorates white matter integrity by enhancing cytotoxic CD8⁺ T-cell activation.

Aim

Methods

Results

Conclusion

Publications

Perioperative stroke deteriorates white matter integrity by enhancing cytotoxic CD8<sup>+</sup> T-cell activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Perioperative stroke deteriorates white matter integrity by enhancing cytotoxic CD8+ T-cell activation.

Aim

Methods

Results

Conclusion

Publications

Perioperative stroke deteriorates white matter integrity by enhancing cytotoxic CD8<sup>+</sup> T-cell activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Perioperative stroke deteriorates white matter integrity by enhancing cytotoxic CD8⁺ T-cell activation.