Neutralizing serum amyloid A1 as a therapeutic strategy for traumatic brain injury

Abstract

Traumatic brain injury (TBI) is the most common cause of disability for millions of people worldwide. It is not only a health problem, but also an economic problem, as there is no effective treatment yet and the sequelae last for the rest of the patient’s life. After a TBI, acute phase proteins (APP) like serum amyloid A1 (SAA1) are released into the serum, promoting neuroinflammation among other things. It has been recently demonstrated that SAA1 binds to TLR4 and activates the production of proinflammatory cytokines, which in turn increases the production of SAA1. TAK242 administration, an antagonist of TLR4, shows protective effects in mice models after a TBI. Therefore, we hypothesize that using a molecule to neutralize SAA1 in serum will also reduce the neurological severity score (NSS) after inducing the closed head injury (CHI). The results showed that the intraperitoneal administration of this molecule can reduce the neurological damage in animals after TBI. Regarding the effects of this molecule at the inflammatory level, we have seen that the administration of this inhibitory compound of the SAA1 pathway produces a decrease in the gene expression of proinflammatory cytokines (IL-1β, IL6 and TNFα). This study demonstrates that SAA1 blockade can reduce neurological damage and the inflammatory genetic profile after trauma in an animal model.