D‐cycloserine improves functional recovery and reinstates long‐term potentiation (LTP) in a mouse model of closed head injury

Traumatic brain injury triggers a massive glutamate efflux, activation of NMDA receptor channels, and cell death. Recently, we reported that NMDA receptors in mice are down‐regulated from hours to days following closed head injury (CHI), and treatment with NMDA improved recovery of motor and cognitive functions up to 14 d post‐injury. Here we show that a single injection of a low dose of D‐cycloserine (DCS), a partial NMDA receptor agonist, in CHI mice 24 h post‐injury, resulted in a faster and greater recovery of motor and memory functions as assessed by neurological severity score and object recognition tests, respectively. Moreover, DCS treatment of CHI mice led to a significant improvement of hippocampal long‐term po‐tentiation (LTP) in the CA1 region that was completely blunted in CHI control mice. However, DCS did not improve CHI‐induced impairment in synaptic gluta‐mate release measured by paired pulse facilitation (PPF) ratio in hippocampal CA1 region. Finally, CHI‐induced reduction of brain‐derived neurotrophic factor (BDNF) was fully restored following DCS treatment. Since DCS is in clinical use for other indications, the present study offers a novel approach to treat human brain injury.–Yaka, R., Biegon, A., Grigoriadis, N., Simeonidou, C., Grigoriadis, S., Alexandrovich, A. G., Matzner, H., Schumann, J., Trembovler, V., Tsenter, J., Shohami, E. D‐cycloserine improves functional recovery and reinstates long‐term potentiation (LTP) in a mouse model of closed head injury. FASEB J. 21, 2033–2041 (2007)