differentiation, and maintenance of function in differ- ent neuronal populations (44, 47). BDNF is a critical regulator of transcription-dependent adaptive neuro- nal responses, such as LTP (48, 49). Earlier studies have shown that activation of NMDARs lead to increased expression of BDNF (50, 51). This effect appears to involve neuronal rather than astrocytic release of BDNF (52, 53). Therefore, the results of the present study raise the following hypothesis as for the consequences of DCS injection; first, DCS activates NMDARs and as a result improves channel function, either by increasing the number of channels on the membrane or increas- ing the activity of existing channels, or both. Second, increased NMDARs channel activity leads to an increase in BDNF levels, which initiates a positive feedback loop to further enhance the function of hippocampal NMDARs.
In conclusion, we propose that LTP is one of the mechanisms through which cognitive performance is impaired after CHI, and that activation of NMDAR at the subacute phase may rescue their function. The extended loss of NMDAR function provides a therapeu- tic window of at least 24 h for the treatment of cognitive and neurological deficits after head injury and may offer benefit to brain-injured patients.
The authors would like to thank Mrs. Olga Touloumi for her technical assistance. This work was supported by the National Institute of Health grant R01 NS 050285-01 A2 (A.B.)
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