PDCD1 Signaling in Microglia Can Reduce Neuroinflammation and Apoptosis Induced by Traumatic Brain Injury by Regulating PI3K/Akt Signaling Pathway, Thereby Alleviating Neurological Dysfunction.

Following traumatic brain injury (TBI), inflammation of the nerve and death of nerve cells are intimately associated with the unfavorable prognosis of TBI patients. This study aims to examine the function of programmed cell death protein-1 (PDCD1) signaling in neuroinflammation and nerve cell death following TBI in mice, as well as its impact on the recuperation of cognitive, memory, and motor capabilities, and to initially analyze its underlying mechanism. In vivo investigations employed a controlled cortical impact (CCI) murine model. BV-2 cells were activated with lipopolysaccharide (LPS) to create an in vitro model of microglial inflammation. The outcome indicates that TBI significantly and temporarily increased the expression of PDCD1 in vivo, with PDCD1 mostly expressed in microglia and neurons, but not in astrocytes. Knockdown of PDCD1 led to an increase in the protein expression levels of IL-1β, iNOS, and Bax, whereas the levels of Bcl-2, p-PI3K, and p-Akt dropped. Nonetheless, the overexpression of PDCD1 yielded contrary outcomes; furthermore, LY294002 may partially counteract the effects of PDCD1 overexpression and diminish its expression levels. And the results of further cell experiments in vitro were consistent with those in vivo. PDCD1 expression is elevated in both in vivo TBI models and in vitro microglial inflammation models. Moreover, PDCD1 mitigates neuroinflammation and nerve cell death, at least partially, via the PI3K/Akt pathway.