**2. Neuroinflammation in the Post-Ischemic Brain**

Numerous studies have shown an inflammatory response in brain tissue to local or complete ischemia in animals and humans [8,26,27,41–45]. The severity and extent of the neuroinflammation depends on the site, area, course, and type of the ischemic brain injury. Inflammation following ischemic brain injury in rats surviving 2 years after global cerebral ischemia showed different severity of microglia and astrocyte responses in different brain structures. In these animals, the study revealed significant astrocyte activation in the CA1 and CA3 areas of the hippocampus and the dentate gyrus, in the motor and sensory cortex, and in the striatum and thalamus, while microglial activation was only seen in the CA1 and CA3 areas of the hippocampus and in the motor cortex. In areas of the brain sensitive to ischemia, microglia and astrocytes showed increased activation at the same time, while in areas resistant to ischemia, only astrocytes were activated. Thus, there is strong evidence of less intense inflammation in ischemia-resistant areas of the brain. Neuroinflammatory processes are supported by microglia and astrocyte activity for up to 2 years in postischemic brain neurodegeneration. The study therefore revealed a chronic effect of brain ischemia on the neuroinflammatory response in the rat brain up to 2 years after the injury [27]. In another study, immunostaining confirmed the presence of T lymphocytes in the ischemic hippocampus and striatum in long-surviving animals after an ischemic episode [26]. The above observations indicate a persistent dysfunction of the blood–brain barrier, which in the long run may still allow T lymphocytes to pass from the blood to the post-ischemic brain. Such processes are supported by microglia activity up to 2 years after ischemia [27]. In addition, these animals showed increased expression of neurogenesis markers and the migration of neuroblasts in the subventricular zone [26]. Thus, the balance of degenerative processes and inflammation surveillance with neurogenesis may be decisive for long-term survival after cerebral ischemia [26]. Brain ischemia induces neuronal necrosis and apoptosis, which triggers an inflammatory response controlled by the release of ROS, cytokines, and chemokines. This process develops not only in the brain but also in the microcirculation and involves several types of cells, such as innate microglia immune cells, adaptive immune cells, and lymphocytes, enhancing neuronal death [8,41]. As a result of neuroinflammation in the brain, the secretion of many cytokines increases both in damaged brain tissue and in peripheral blood. These cytokines are involved in the progression of post-ischemic brain neurodegeneration and influence disease severity and neurological outcomes [8,41].
