Fig. 1

a Normal synapse, with physiological variations in TNF controlling glutamate levels in synaptic cleft through homeostatic activity of glutaminase and re-entry transporter proteins. b Excess cerebral TNF enhancing glutaminase and inhibiting re-entry transporter proteins, causing glutamate to accumulate to excitotoxic toxic levels. c Glutamate excess rapidly dispersed from synaptic cleft due to glutaminase reduction plus re-entry protein upregulation. Both occur together after treatment with intracerebral (perispinal) anti-TNF biologicals or non-specific TNF inhibitors (dithio-thalidomines, nilotinib, cannabinoids) by other routes. Glutaminase reduction alone occurs with DON, and re-entry protein upregulation alone with ceftriaxone and riluzole