FIGURE 6.

The Central nervous system (CNS) inflammation. Peripheral immunocytes and cytokines infiltration into the CNS contribute to the CNS inflammation. Activated astrocyte releases IL‐6 and GM‐CSF that induce microglia activation to produce additional IL‐1β, IL‐6, and TNF‐α, which further influence neuron function. Increased GFAP and S100b suggest astrocyte activation and injury, while downregulation of galectin‐1 indicates reduced control of microglia activation by astrocyte. Upregulated OX‐6 and OX‐42 on microglia indicate activated status. Astrocyte activation and injury induce glutamine accumulation and decomposition on mitochondria membrane, which lead to ATP depletion and mitochondria permeability transition. Energy insufficiency induces compromised water control by APQ4 and leads to astrocyte swelling. Dysfunctional astrocyte promotes extracellular glutamate accumulation by increased released and inhibited re‐uptake. Accumulative glutamate along with neuron GABA receptor endocytosis caused by TNF‐α increase neuronal excitability through NMDA and AMPA receptor in Ca²⁺ dependent manner. Abnormal neuron functions present with corresponding symptoms of immune effector cell‐associated neurotoxicity syndrome (ICANS) after chimeric antigen receptor T‐cell (CAR‐T) treatment.