Sodium butyrate improves the effects of brain injury in a small-for-gestational-age rat model by activating the JAK1/STAT3 pathway.

The mechanisms of cognitive impairment in small-for-gestational-age (SGA) infants remain unclear. We investigated clinical effects and mechanisms of sodium butyrate (NaB) treatment in a SGA rat model. Behavioral tests, immunohistochemistry, and molecular biology analysis were performed on controls and on SGA rats divided into SGA, SGA + NaB, and SGA + NaB + upadacitinib (a JAK1 inhibitor) groups. Compared to the controls, SGA rats showed weakened neuroreflexes, impaired short-term learning and memory, and manifestations of anxiety and depression. Hippocampal neurons were damaged and apoptotic, and expression of pro-inflammatory factors IL-6 and TNF-α and the JAK1/STAT3 inflammatory pathway were increased in the SGA rats. NaB improved neuroreflexes, learning and memory, anxiety and depressive behaviors, and apoptosis of hippocampal neurons in SGA rats whereas NaB + upadacitinib treatment did not significantly improve these indicators. NaB upregulated JAK1/STAT3 pathway expression in hippocampal neurons of SGA rats and downregulated IL-6 and TNF-α expression; NaB + upadacitinib treatment had the opposite effects. Thus, NaB improved the neurobehavioral performance of SGA rats and reduced damage of hippocampal neurons by activating the JAK1/STAT3 pathway. This study reveals a mechanism of cognitive impairment in SGA infants, providing possible new therapeutic targets.