Inflammation Of The Brain And Spinal Cord – Since inflammation in the brain contributes to a number of neurological and psychiatric disorders, the causes of neuroinflammation are being studied extensively. The causes of neuroinflammation can be divided into the following categories: viral infections, autoimmune diseases, inflammation of peripheral organs, stress, metabolic disorders, and lifestyle. In particular, the effects of neuroinflammation due to the inflammation of the peripheral organs are still unknown. Many diseases, such as inflammatory bowel disease, chronic obstructive pulmonary disease, rheumatoid arthritis, dermatitis, chronic fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), cause neuroinflammation through several mechanisms. The peripheral mechanisms of neuroinflammation include disruption of the blood-brain barrier, activation of glial cells associated with the immune system, and effects on the autonomic nervous system through the organ-brain axis. In this review, we review previous studies on systemic inflammation and neuroinflammation, focusing on the regions of the brain that are susceptible to inflammation.

Brain inflammation has attracted much attention due to its involvement in several diseases at several stages of life. For example, some research has shown a relationship between neuroinflammation and several types of dementia (Bevan-Jones et al., 2020). Maternal diseases have been shown to cause neuroinflammation in the fetal brain, leading to schizophrenia (Brown et al., 2004) and neurodevelopmental disorders such as autism spectrum disorder (ASD) (Slawinski et al., 2018). In addition, a study on major depressive disorder (MDD) showed that C-reactive protein (CRP) can be a marker of neuroinflammation and inflammation and is suitable to guide immunotherapy targeting inflammatory cytokines such as TNF-α and IL -6. patients with MDD (Felger et al., 2020). Therefore, neuroinflammation has a significant impact on psychological symptoms, and we need to control neuroinflammation.

Inflammation Of The Brain And Spinal Cord

Inflammation Of The Brain And Spinal Cord

Repeated insults can cause neuroinflammation, such as viral infections in the central nervous system (Klein et al., 2019), chronic inflammation [sore throat (Schrepf et al., 2018), intestinal inflammation (Do and Woo, 2018)], and autoimmune disorders. In terms of autoimmune disease, the most common example would be paraneoplastic limbic encephalitis (PLE). In patients with certain types of cancer, such as small cell lung cancer, the immune system interacts with specific onconeural antigens can cause damage to neural tissue and cause neuroinflammation (Bien et al., 2012; Zhang et al., 2013). ). Taken together, persistent systemic inflammation increases the likelihood of neuroinflammation. Meanwhile, factors such as lifestyle contribute to neuroinflammation. An unhealthy diet has been shown to affect the gut microbiota, alter the blood-brain barrier (BBB), and induce neuroinflammation (Dutheil et al., 2016; Spielman et al., 2018). Obesity, metabolic syndrome, and diabetes can accelerate the metabolism of neuronal cells, which produce reactive oxygen species (ROS) that cause oxidative stress and therefore neuroinflammation (de Heredia et al., 2012; Van Dyken and Lacoste , 2018). In addition, emotional stress has been shown to increase the levels of several cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) to cause neuroinflammation and cause depression or anxiety. Sleep deprivation has also been suggested as a risk factor for neuroinflammation (Curcio et al., 2006; Hurtado-Alvarado et al., 2016). Therefore, anyone can be at risk of neuroinflammation, with or without disease. Therefore, it is important to understand how neuroinflammation develops.

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Among the known causes of neuroinflammation, the influence of systemic inflammation on neuroinflammation has not been investigated. Recent evidence suggests that chronic inflammation causes systemic inflammation that can increase the synthesis of pro-inflammatory cytokines and mediators that promote inflammation, causing neuroinflammation in the diseased brain (Perry, 2004; Aktas et al., 2007). Another study showed a relationship between systemic inflammation and microglial activation through several neurotoxic factors, including TNF-α, IL-1, and ROS (Hoogland et al., 2015). Microglia activation is a key driver of brain inflammation. It has been reported that chronic inflammation breaks down the BBB, damaging the separation between the central and peripheral nervous system, leaving the central nervous system (CNS) vulnerable (Abbott et al., 2010). The intimate gut-brain relationship, which includes neural communication, hormones, and the immune system also play an important role in neuroinflammation caused by systemic inflammation (Abautret-Daly et al., 2018). Therefore, the persistence of chronic inflammation leads to systemic inflammation and an increase in pro-inflammatory factors and disruption of the immune system of the brain tissue, all of which lead to neuroinflammation.

Another interesting fact is that the inflammatory site is often less in the case of neuroinflammation due to systemic inflammation. Taking PLE as an example, although antigens are expressed throughout the brain, neuroinflammation is limited to the limbic system (Bien et al., 2012; Zhang et al., 2013). In addition, previous research has also shown that inflammatory bowel disease (IBD) can cause neuroinflammation from the bottom-up, and this depends on the brain region: the regulation of cyclooxygenase-2 (COX-2) mRNA, glial. fibrillary acidic protein (GFAP) mRNA, and GFAP expression during exposure to dextran sulfate sodium (DSS) in the hippocampus; upregulation of COX-2 mRNA only three days after DSS treatment in the hypothalamus; Decreased brain-derived neurotrophic factor (BDNF) and COX-2 mRNAs in the amygdala (Do and Woo, 2018). In previous studies, the parts of the brain affected are few such as the cortex, striatum, thalamus, hippocampus, amygdala. Therefore, it is important to clarify the differences in the pathophysiology of neuroinflammation in different areas of involvement.

A deeper understanding of this mechanism will help develop new treatments for neuroinflammation-related diseases. A meta-analysis showed that adjunctive anti-inflammatory treatment affects psychotic symptoms, although no improvement was found in anti-inflammatory treatment (Jeppesen et al., 2020). After administration of anti-inflammatory drugs, they remain in the circulating blood. Plasma protein binding reduces the absorption of Non-Steroidal Anti-Inflammatory Drug (NSAID) by reducing the free NSAID concentration in the blood. As small non-binding molecules can pass through the BBB, it is very difficult for therapeutic molecules to enter the CNS (Rhea and Banks, 2019). As a result, although the dose of anti-inflammatory drugs administered through intraperitoneal injection or intravenously increases significantly, less anti-inflammatory substances enter the brain. Taking into account the safety of the drug, a dose exceeding the recommended level of immunity is not allowed. In order to overcome this problem, the research group has developed a new method of drug administration – spinal delivery and transdermal patch on the neck and cervix (Lehrer and Rheinstein, 2019). Medicines administered by the aforementioned method diffuse through the intervertebral spaces and enter the cerebrospinal fluid, which is not affected by the BBB.

In this review, we summarize previous studies on systemic inflammation and neuroinflammation in detail, focusing on brain regions that are susceptible to inflammation. This interaction may be a reflection of neuroinflammation caused by systemic inflammation. By identifying important points or methods in this process, we can suggest further research on this topic. If the mechanism can be identified in the future, it will also be easier to prevent the occurrence of neuroinflammation, reducing patient suffering, drug costs, and social problems.

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Previous studies have shown that inflammation of several peripheral organs leads to inflammation in the brain. Colitis may be the most talked about disease that causes neuroinflammation. In an animal model of colitis (Abautret-Daly et al., 2018; Ticinesi et al., 2018; Peppas et al., 2021; Craig et al., 2022), neuropsychiatric symptoms such as spatial and memory disturbances (Peppas et al. ., 2021), depression (Riazi et al., 2015; Abautret-Daly et al., 2018; Do and Woo, 2018; Peppas et al., 2021), cognitive impairment (Riazi et al., 2015; Do and Woo, 2018; Ticinesi et al., 2018), changed behaviors related to anxiety (Reichmann et al., 2015), and anxiety (Riazi et al., 2015; Abautret-Daly et al., 2018; Peppas et al. ., 2021) ) observed in behavioral experiments. The areas affected in the brain are the hippocampus (Reichmann et al., 2015; Riazi et al., 2015; Zonis et al., 2015; Do and Woo, 2018; Han et al., 2018; Han et al., 2020; ; Peppas et al., 2021), cortex (Han et al., 2018; Peppas et al., 2021), amygdala (Reichmann et al., 2015; Do and Woo, 2018), and hypothalamus (Reichmann et al., 2015; Do and Woo, 2018). Comparative studies also confirm this relationship between bowel disease and brain tumors (Table 1) (Dolapcioglu and Dolapcioglu, 2015).

Some animals have been used to demonstrate the relationship between inflammatory diseases and neuroinflammation, such as periodontal disease (PD), gastritis, pancreatitis, arthritis, cystitis, and atopic dermatitis (Lin et al., 2018; Albaret et al., 2020; Ding et al. al., 2020; Furutama et al., 2020; Matsushita et al., 2021; Shin et al., 2021). Brain tumor regions and neuropsychiatric symptoms in these subjects are listed in Table 2. In addition, some clinical trials also provided preliminary evidence that primary biliary cholangitis (PBC) (Zenouzi et al., 2018), a chronic fatigue syndrome / myalgia encephalomyelitis. (CFS/ME) (Nakatomi et al., 2014), and chronic obstructive pulmonary disease (COPD) (Pelgrim et al., 2019) have some relationship with neuroinflammation.

When it comes to neuroinflammation, factors related to the immune system and disruption of the BBB are widely accepted as important causes. Systemic inflammation leads to an increase in inflammatory cytokines such as IL-6, IL-18, TNF-α, and growth factor oncogene-α (GRO-α)/chemokine ligand 1 (CXCL1) (Reichmann and

Inflammation Of The Brain And Spinal Cord