Table 1.
The pathophysiology of neuroinflammation in stroke
| Pathophysiology | Mechanism | Outcome |
|---|---|---|
| Endothelial cell activation | Release of von Willebrand factor (vWF) stored in Weibel-Palade bodies, interaction with leukocytes | Platelet activation, leukocyte recruitment, capillary no-reflow |
| ROS production | Acute hypoxia and glucose deprivation, cytosolic enzyme and mitochondrial activity | Upregulation of AMPA and glutamate receptors, excitotoxicity, neuronal apoptosis, pro-inflammatory cytokine production |
| Inflammatory cascade activation | P-selectin interaction with P-selectin glycoprotein ligand-1 on leukocytes, immune cell recruitment | Increased cerebral inflammation, progression of ischemic injury |
| Monocyte and macrophage function | Expression of anti- and pro-inflammatory cytokines | Dual effects on inflammation, phagocytosis of degraded cells |
| T-cell function | IL-17 secretion by CD4 and CD8 cells | Aggravation of ischemic injury |
| Platelet activation | Granule release, interaction with leukocytes | Increased platelet activation, pro-inflammatory cytokine release, formation of platelet-leukocyte complexes |
| Neutrophil infiltration | Expression of adhesion molecules, cytokines and chemokines | Increased inflammation, formation of neutrophil extracellular traps (NETs) |
| Microglial activation | Release of pro- and anti-inflammatory cytokines, phagocytosis of apoptotic cells | Dual effects on inflammation, modulation of neurodegeneration |
| Astrocyte activation | Release of pro- and anti-inflammatory cytokines, upregulation of GFAP | Dual effects on inflammation, modulation of neurodegeneration, formation of glial scars |
| Blood-brain barrier dysfunction | Disruption of tight junctions, infiltration of immune cells | Increased inflammation, neurodegeneration |
| Cytokine and chemokine release | Production by immune cells, astrocytes, endothelial cells, neurons | Amplification of inflammation, recruitment and activation of immune cells, modulation of neurodegeneration |
| Complement system activation | Release of complement proteins, interaction with immune cells | Amplification of inflammation, modulation of neurodegeneration, potential for therapeutic targeting |
This table is not exhaustive and only includes some of the key pathophysiological processes involved in neuroinflammation in stroke