CD28 and brain ischemia: For instance, HMF showed neuroprotection against brain ischemia by inducing BDNF production and anti-inflammatory actions (Okuyama et al., 2014; Okuyama et al., 2015) and demonstrated an immunomodulatory function for the reduction of interleukin-4 expression in CD3/CD28-stimulated spleen cells in mice (Nakajima et al., 2016).