Neuroinflammation in Post-Ischemic Neurodegeneration of the Brain: Friend, Foe, or Both?

Abstract

One of the leading causes of neurological mortality, disability, and dementia worldwide is cerebral ischemia. Among the many pathological phenomena, the immune system plays an important role in the development of post-ischemic degeneration of the brain, leading to the development of neuroinflammatory changes in the brain. After cerebral ischemia, the developing neuroinflammation causes additional damage to the brain cells, but on the other hand it also plays a beneficial role in repair activities. Inflammatory mediators are sources of signals that stimulate cells in the brain and promote penetration, e.g., T lymphocytes, monocytes, platelets, macrophages, leukocytes, and neutrophils from systemic circulation to the brain ischemic area, and this phenomenon contributes to further irreversible ischemic brain damage. In this review, we focus on the issues related to the neuroinflammation that occurs in the brain tissue after ischemia, with particular emphasis on ischemic stroke and its potential treatment strategies.

Neuroinflammation in Post-Ischemic Brain

“…Some reactive astrocytes change into nonprofessional phagocytes after an ischemic stroke and "clean up" the infarct region (50). In physiological conditions, astrocytes consume excessive glutamate from extracellular space and convert it to glutamine for neural reuse, and upon brain injury their capability for uptake may be impaired (2). The role of astrocytes in preventing excitotoxic glutamate elevation was confirmed in tMCAO rat model (51).…”

“…Upon brain ischemia, they undergo morphological and phenotypic changes, continuously changing and responding to local stimuli (17,19). Microglia in the post-ischemic parenchyma move towards the ischemic lesion and remain in close proximity to the neurons in a process known as "capping," which aids in early identification and quick phagocytic clearance of dead neurons after neuronal death (2,19).…”

“…In the post-ischemic brain, activated microglia become amoeboid and have a functional macrophage role releasing cytokines and secreting extracellular matrix metalloproteinases (MMPs) that could increase the permeability of the BBB, worsening post-ischemic injury (2).…”

“…Stroke is the second leading cause of death and long-term disability. It is associated with significant clinical and socio-economic implications, emphasizing the need for elucidation of the pathophysiological mechanisms, and effective therapies (1,2). Cerebrovascular illness, especially stroke, causes a large percentage (47-67 %) of disability-adjusted life years and deaths worldwide (3).…”

TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

“…However, clinical trials aiming at inhibiting neuroinflammation in stroke patients have been unsuccessful so far [ 282 , 283 ]. In fact, in recent years the role of post-ischemic neuroinflammation has been shown to be more complex and both beneficial and detrimental depending on the animal model, species, and type of elicited immune response ( Figure 5 ) [ 284 , 285 , 286 , 287 ].…”