Animal Models for Neuroinflammation and Potential Treatment Methods, 2022, Tamura et al

Andy

Retired committee member
[This seems to be only very tenuously about ME/CFS]

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown etiology and without effective treatment options. The onset of ME/CFS is often associated with neuroinflammation following bacterial or viral infection. A positron emission tomography imaging study revealed that the degree of neuroinflammation was correlated with the severity of several symptoms in patients with ME/CFS. In animal studies, lipopolysaccharide- and polyinosinic-polycytidylic acid-induced models are thought to mimic the pathological features of ME/CFS and provoke neuroinflammation, characterized by increased levels of proinflammatory cytokines and activation of microglia.

In this review, we described the anti-inflammatory effects of three compounds on neuroinflammatory responses utilizing animal models. The findings of the included studies suggest that anti-inflammatory substances may be used as effective therapies to ameliorate disease symptoms in patients with ME/CFS.

Open access, https://www.frontiersin.org/articles/10.3389/fneur.2022.890217/full
 
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These findings suggest that peripheral and central administration of LPS and poly I:C can induce inflammatory responses in the brain and can be used as neuroinflammatory animal models for the screening of anti-inflammatory drugs and foods.


This review describes the anti-inflammatory effects of three different types of compounds: IL-1 receptor antagonist (IL-1ra), minocycline, and 6- (methyl sulfinyl) hexyl isothiocyanate (6-MSITC).
 
There are no new studies here, it's a review of previous work, mostly by these authors. We'd have to look at the references to see how strong the results are. The conclusion suggests the authors are looking to trial these treatments in people with ME/CFS.

IL-1ra is a member of the IL-1 family and is known as an endogenous competitive antagonist for IL-1 receptors, that is, IL-1ra counteracts the action of IL-1β (52). We previously investigated that poly I:C-induced decrease in locomotor activity was completely blocked by intracerebroventricular (i.c.v) infusion of recombinant IL-1ra (40). Also, we demonstrated that the recovery from a decrease in spontaneous activity during poly I:C-induced neuroinflammation was significantly delayed by i.c.v. infusion of a neutralizing antibody for endogenous IL-1ra. These results indicate that endogenous IL-1ra in the brain has an important role in the prevention of prolonged inflammation

Minocycline is known as a second-generation and semi-synthetic tetracycline antibiotic. Minocycline is quickly absorbed into the body, penetrates the BBB, and affects many biological actions (differing from its antibiotic action) both in vivo and in vitro, including the following: attenuation of BBB breakdown by inhibiting the production of matrix metalloproteinase-9; functional improvement after traumatic brain injury via suppression of aquaporin-4 production; relieve white matter injury in the neonatal rat brain by suppression of IL-1β and TNF-α production; neuroprotection from ischemic brain damage; alleviation of LPS-induced depressive-like behavior; and suppression of NOx production in cultured microglia under hypoxia (55, 56). In our study, we demonstrated that intraperitoneal pretreatment with minocycline (20 mg/kg/day, 3 consecutive days) attenuated poly I:C-induced IL-1β mRNA expression in rat brain, transient fever, and decrease in locomotor activity (57). Further, it was also reported that intrathecal pretreatment with minocycline attenuated chronic stress-induced muscular hyperalgesia and mechanical allodynia by suppression of spinal cord microglial activation in rat model for ME/CFS (58). These observations suggest that minocycline could be a new drug for improving some deficits seen in neurological disorders (Figure 1).

Although the mechanisms underlying minocycline's anti-inflammatory effect on neuroinflammation are not well-understood, once severe neuroinflammation occurs, suppression might prove to be difficult. Indeed, we could not demonstrate suppression of neuroinflammation by minocycline after poly I:C-injection without pretreatment (57).

Finally, 6-MSITC derived from Wasabi (Wasabia japonica) is a naturally occurring compound that has several biological functions, including anti-inflammatory, antitumor, and anticoagulant activities. In vitro studies have shown that 6-MSITC treatment inhibited activation of murine macrophage cells following the application of LPS (59), and attenuated TNF-induced upregulation of IL-6 in human umbilical vein endothelial cells (60). In addition, 6-MSITC alleviated several inflammatory responses in a murine model of inflammatory bowel disease, known as chronic inflammatory disorders of the gastrointestinal tract (61). However, the anti-inflammatory effects of 6-MSITC on LPS- or poly I:C-induced neuroinflammation have not been characterized. In our studies, long-term use of 6-MSITC relieved neuroinflammatory responses following a peripheral injection of poly I:C (Figure 1), but did not show anti-inflammatory effects on neuroinflammation following a central LPS challenge (62). The observed discrepancy is unclear but warrants further investigation. Still, these findings suggest that 6-MSITC may ameliorate the neuropsychological symptoms of ME/CFS with viral infections.
 
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