**4. Interaction of Inflammatory Cells in the Post-Ischemic Brain**

The release of IL-6 and TNF-α by area(s) of brain ischemia enhances the invasion of neutrophils into the brain, which intensifies the blood–brain barrier permeability, and an increased number of neutrophils in the blood is associated with the extent of the infarction [101]. Moreover, the role of microglia after brain ischemia depends on the state of cell polarity. The dominance of the M1 phenotype correlates with extensive post-ischemic damage, increased anaerobic glycolysis, and activation of hypoxia-inducible factor 1α. Polarization of the microglial cells to the M1 phenotype and the resulting increased generation of IL-23 favor the recruitment and stimulation of γδ T lymphocyte cells, which play an unfavorable role within acute ischemic stroke [8]. The results of studies on experimental models of brain ischemia confirm that γδ T lymphocyte cells are pathogenic for the brain due to IL-17 secretion and stimulation of inflammatory changes [102]. Moreover, the release of anti-inflammatory cytokines by microglia such as IL-10 and TGF-β

promotes the recruitment of regulatory lymphocytes that perform immunomodulatory and immunosuppressive functions in the ischemic brain [26]. Evidence supports a beneficial function of CD4+ lymphocyte cells in experimental brain ischemia [103]. Inflammatory cell interactions are very complex and involve intercellular crosstalk by mechanisms that are not fully understood. Evidence suggests that inflammation plays a bivalent role in the development of post-ischemic brain neurodegeneration, promoting neuronal loss and healing of post-ischemic lesions. As a consequence, neuroinflammation may be a promising target for the future treatment of stroke.
