*4.2. Neuroinflammatory Process*

Through emerging evidence, the role of neuroinflammation in neurological diseases has been well documented, and by controlling the key factors that are responsible for the immune and inflammation processes, can serve as a key to the prevention and delay of most late-onset CNS disorders [104]. Poor quality of life and unhealthy food habits have led to the onset and progression of several diseases such as stroke, hypertension, diabetes, obesity, etc., which causes alteration in lipid hormones, adipokines, and inflammatory cytokines, thereby inducing adverse regulatory responses [105]. These metabolic disorders also regulate chronic activation of the pro-inflammatory cytokines even in the CNS, which makes the population vulnerable to neurological disorders.

A correlation between neurological disorders such as anxiety and depression and proinflammatory cytokines has been developed, which indicates their chief role in the instigation of cognitive dysfunction, thereby favoring neurodegradation. An increase in the level of peripheral inflammatory markers such as interleukin (IL)-6 and IL-8 is associated with mortality from suicide and depression. The complement cascade of the activation of microglial cells in response to pruning synapses is a biological mechanism that commonly occurs in neuroinflammatory processes and the development of a healthy brain. The generation of neurotrophic factors can be compromised by the activation of the immune system and lead to microglial cell-mediated secretion of cytotoxic factors.

Microglial cells are the main agents involved in neuroinflammation, with the second being astroglia cells [106]. Astrocytes are responsive to all forms of CNS insults due to the reactive astrogliosis process. The activation of astrocytes is highly complex, multistage, and a pathogen-specific reaction, and mainly aims for neuroprotection and recovering the injured and damaged neuronal tissue. It is evident that the sustained inflammatory responses in the central nervous system support the major contribution of astrocytes and microglia to neurological disease progression, thereby implying their chief role as effectors of neuroinflammation in neuron dysfunction and cell death [107]. Endothelial cells, neurons, and many other cells act as receptors for cytokines and inflammatory mediators, thereby activating the signaling of inflammatory responses in the brain.
