Fig. 1.

Schematic overview of the general mechanisms of neuroinflammation after ischemic stroke, Ischemic stroke occurs following a blood vessel occlusion due to a thrombus or embolus. Brain ischemia results in oxygen and ATP depletion and subsequently acute neuronal damage in the infarcted tissue. Then, danger-associated molecular patterns (DAMPs) are released by injured and dying neurons which in turn activate microglia, astrocytes, and endothelial cells, leading to the produce the proinflammatory factors such as IL-1, IL-6 and TNF, reactive oxygen species (ROS), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF). These molecules trigger BBB dysfunction by endothelial downregulation of tight junction proteins and upregulation of cell adhesion molecules including vascular cell adhesion molecules (VCAM) and intracellular adhesions molecule-1 (ICAM-1), leading to migration and infiltration of circulating leukocytes, mainly neutrophils through the disrupted BBB into the ischemia area. Activated neutrophils release proinflammatory mediators which cause further activation of microglia and astrocytes. This pathological cascade leads to neuronal cell death, edema, and hemorrhage, which in turn cause further neuroinflammation and tissue damage