The stroke will aggravate cerebrovascular dysfunction, leading to the emergence of brain inflammation and the death of nerve cells.[53] Cytokines (IL-1, IL-2, IL-6, TNF- α) could promote the gene expression of indoleamine 2,3-dioxygenase, metabolize tryptophan into canine uric acid, transfer tryptophan from 5-HT synthesis, reduce the content of 5-HT in the frontal cortex and basal ganglia.[54] The physiological change could contribute to the onset of depression. Here, TNF is linked to major depressive disorder.