**3. Pro- and Anti-Inflammatory Cytokines and Inflammatory Cells in the Post-Ischemic Brain**

#### *3.1. Cytokines*

The occurrence of generalized inflammatory changes following brain ischemia is a relatively well-known phenomenon [46–49]. Cytokines such as IL-6 and TNF-α appear to be key mediators of this phenomenon [46–49]. Increased release of pro-inflammatory cytokines has been observed in the blood of people with ischemic stroke and has been correlated with a larger area of cerebral ischemia and worse outcomes [46,47,49]. Increased concentration of IL-6 in blood and cerebrospinal fluid is associated with an increase in neurological symptoms, a greater volume of infarction, and a worse prognosis [49]. In addition, elevated levels of TNF-α in the cerebrospinal fluid and blood in people with stroke have been associated with deteriorating neurological symptoms, an increase in infarct size, and worse clinical outcomes [48]. In contrast to the pro-inflammatory cytokines, IL-10 and IL-4 are anti-inflammatory cytokines. The exact relationship between pro- and antiinflammatory cytokines and their relevance to clinical outcomes in ischemic stroke patients remain unexplained. However, this balance is disturbed in the early stages of an ischemic stroke [8]. This supports the study of elevated pro-inflammatory IL-6 in the blood at 12 h after cerebral ischemia in stroke patients compared to controls, and this increase has been correlated with severe neurological deficits and worse outcomes [50]. In conclusion, increased IL-6 and reduced IL-10 concentrations are present in the early stroke period

and are associated with a degree of neurological deficit and stroke outcome [50]. This observation confirms the interaction between pro- and anti-inflammatory cytokines in the first phases of ischemic stroke, and the advantage of the balance in favor of inflammation results in more severe neurological deficits. Interestingly, at the moment, we cannot precisely define the phenomena modulating this interaction.
