Fig. 9.

Glutamate induced neurotoxicity after SAH. Schematic illustration of channels and receptor dysfunction after SAH. Increased extracellular glutamate concentration generated after SAH leads to downregulation of GLT-1, GLAST, and EAAC1, resulting in neuronal degeneration. Dysfunction of mGluR2 may play a role in cognitive deterioration. Activation of extra-synaptic GluN1/GluN2B containing N-Methyl-D-aspartate receptors (NMDARs) leads to increased intracellular Ca²⁺ accumulation. Another glutamate receptor, mGluR1, activates IP3 and releases Ca²⁺ from the endoplasmic reticulum. Increased expression of NHE1 leads to intracellular accumulation of Na⁺, which causes Ca²⁺ entry via Na/Ca exchanger and thus contributes to excessive cytosolic Ca²⁺levels. Increased intracellular Ca²⁺levels lead to increased ROS generation resulting in neuronal injury following SAH. Extracellular glutamate activates mGluR5 and resulting in neuroprotection via increased expression of Bcl-2 and downregulation of Bax. Inhibition of HCN channels probably via exhausted NO signaling facilitates neuronal excitability after SAH