TNF and Hyperglycemia: Diabetic mice with chronic hyperglycemia exhibit enhanced blood-brain barrier (BBB) permeability, microglia activation (Iba-1 immunoreactivity, enlarged microglial somas), and elevated TNF-α and IL-6 production, along with the downregulation of the expression of two synaptic markers, spinophilin and synaptophysin (53, 54).