Lipoxin A 4 Receptor Stimulation Attenuates Neuroinflammation in a Mouse Model of Intracerebral Hemorrhage.
Risa FutokoroMasanori HijiokaMoe ArataYoshihisa KitamuraPublished in: Brain sciences (2022)
Intracerebral hemorrhage (ICH) is caused by the rupture of blood vessels in the brain. The excessive activation of glial cells and the infiltration of numerous inflammatory cells are observed during bleeding. Thrombin is a key molecule that triggers neuroinflammation in the ICH brain. In this study, we focused on lipoxin A 4 (LXA 4 ), an arachidonic acid metabolite that has been reported to suppress inflammation and cell migration. LXA 4 and BML-111, an agonist of the LXA 4 receptor/formyl peptide receptor 2 (ALX/FPR2), suppressed microglial activation; LXA 4 strongly inhibited the migration of neutrophil-like cells in vitro. ALX/FPR2 was expressed on neutrophils in the ICH mouse brain and the daily administration of BML-111 attenuated the motor coordination dysfunction and suppressed the production of proinflammatory cytokines in the ICH mouse brain. On the other hand, BML-111 did not show a significant reduction in the number of microglia and neutrophils. These results suggest that systemic administration of ALX/FPR2 agonists may suppress the neuroinflammatory response of microglia and neutrophils without a change in cell numbers. Additionally, their combination with molecules that reduce cell numbers, such as modulators of leukotriene B 4 signaling, may be required in future studies.
Keyphrases
- induced apoptosis
- cell migration
- oxidative stress
- inflammatory response
- neuropathic pain
- mouse model
- lipopolysaccharide induced
- cell cycle arrest
- cerebral ischemia
- lps induced
- single cell
- brain injury
- traumatic brain injury
- cell therapy
- white matter
- resting state
- endoplasmic reticulum stress
- cognitive impairment
- weight gain
- stem cells
- physical activity
- cell proliferation
- atrial fibrillation
- mesenchymal stem cells
- binding protein
- body mass index
- multiple sclerosis
- bone marrow
- weight loss