Curcumin attenuates neuroinflammatory damage induced by LPS: Implications for the role of S100B

Inflammation is a common feature of neurological disorders that alters cell function in microglia and astrocytes as well as other neuronal cell types. Astrocytes modulate blood flow, regulate glutamate metabolism, and exert antioxidant protection. When responding to inflammatory damage, astrocytes enhance immune cell infiltration and amplify inflammatory responses via the upregulation of cytokine production. Several molecules have been proposed to attenuate neuroinflammation and control neurological diseases. Curcumin gained attention due to its capacity to cross the blood-brain barrier and its well-described anti-inflammatory and antioxidant activities. Our study aimed to understand if oral curcumin administration could protect against central nervous system inflammatory damage induced by intracerebroventricular injection of LPS while focusing on astrocyte function. Despite its poor bioavailability, we found that curcumin reaches the central nervous system, prevents the locomotory damage caused by LPS, and reduces inflammatory signaling via IL-1β and COX-2. Furthermore, we observed that curcumin was protective against LPS-induced S100B secretion in the cerebrospinal fluid and GSH reduction in the hippocampal tissue. However, curcumin could not protect the animals from anhedonia, assessed by the sucrose preference test, and weight loss induced by LPS. Our results indicate that oral curcumin administration exerts a protective anti-inflammatory action in the central nervous system, attenuating the sickness behavior induced by ICV LPS. This work demonstrates that curcumin has an important modulative effect on astrocytes, thus suggesting that astrocytes are critical to the anti-inflammatory effects of curcumin.