FIGURE 3.

Immunometabolic imbalance in the CNS. Leptin and insulin resistance, associated with metabolic disease, can cause immune dysfunctions and increased infection susceptibility. Metabolic imbalance also causes BBB disruption, leading to neuroinflammation and loss of CNS homeostasis, eventually resulting in functional damages to the affected brain regions. While hypothalamic damages can magnify immunometabolic imbalance in the periphery (vicious cycle), hippocampal and cortical damages can cause cognitive impairment. CNS infection-induced brain damages can further enhance the immunometabolic imbalance and cognitive deficits, as part of the vicious cycle.