Title:Arachidonic Acid Derivatives and Neuroinflammation
Volume: 21
Issue: 2
Author(s): Era Gorica and Vincenzo Calderone*
Affiliation:
- Department of Pharmacy, University of Pisa, Pisa, Italy
Keywords:
Neuroinflammation, arachidonic acid, arachidonic acid cascade, prostaglandin, prostacyclin, leukotrienes
Abstract: Neuroinflammation is characterized by dysregulated inflammatory responses localized
within the brain and spinal cord. Neuroinflammation plays a pivotal role in the onset of several neurodegenerative
disorders and is considered a typical feature of these disorders. Microglia perform
primary immune surveillance and macrophage-like activities within the central nervous system. Activated
microglia are predominant players in the central nervous system response to damage related
to stroke, trauma, and infection. Moreover, microglial activation per se leads to a proinflammatory
response and oxidative stress. During the release of cytokines and chemokines, cyclooxygenases
and phospholipase A2 are stimulated. Elevated levels of these compounds play a significant role in
immune cell recruitment into the brain. Cyclic phospholipase A2 plays a fundamental role in the
production of prostaglandins by releasing arachidonic acid. In turn, arachidonic acid is biotransformed
through different routes into several mediators that are endowed with pivotal roles in the
regulation of inflammatory processes. Some experimental models of neuroinflammation exhibit an
increase in cyclic phospholipase A2, leukotrienes, and prostaglandins such as prostaglandin E2, prostaglandin
D2, or prostacyclin. However, findings on the role of the prostacyclin receptors have revealed
that their signalling suppresses Th2-mediated inflammatory responses. In addition, other in
vitro evidence suggests that prostaglandin E2 may inhibit the production of some inflammatory cytokines,
attenuating inflammatory events such as mast cell degranulation or inflammatory
leukotriene production. Based on these conflicting experimental data, the role of arachidonic acid
derivatives in neuroinflammation remains a challenging issue.
