Figure 5.

Negative regulation of GLT-1 by astrocytes HDAC2 leads to dysfunction of glutamate reuptake in the synaptic cleft. In normal condition, the acetylation of histones in astrocytes facilitates the transcriptional regulation of GLT-1. Glutamate in the synaptic cleft is rapidly absorbed into astrocytes to maintain excitability of synapses. The increase of HDAC2 in astrocytes after SAH results in the deacetylation of histones and inhibits the transcription expression of GLT-1. The decrease of GLT-1 expression will lead to the impairment of glutamate reuptake in astrocytes and the long-term accumulation of glutamate in the synaptic space, resulting the dephosphorylation of ionized glutamate receptors GluN2B and GluA1 on the postsynaptic membrane. These eventually result in the long-term inhibition of synaptic excitability and DCI. DCI, delayed cognitive impairment.