D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury.
Title | D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Yaka, R., Biegon A., Grigoriadis N., Simeonidou C., Grigoriadis S., Alexandrovich A. G., Matzner H., Schumann J., Trembovler V., Tsenter J., & Shohami E. |
Journal | FASEB J |
Volume | 21 |
Issue | 9 |
Pagination | 2033-41 |
Date Published | 2007 Jul |
ISSN | 1530-6860 |
Keywords | Animals, Astrocytes, Brain Injuries, Brain-Derived Neurotrophic Factor, Cycloserine, Drug Evaluation, Preclinical, Excitatory Amino Acid Agonists, Excitatory Postsynaptic Potentials, Head Injuries, Closed, Hippocampus, Long-Term Potentiation, Male, Mice, Microglia, Motor Activity, Neuroprotective Agents, Receptors, N-Methyl-D-Aspartate, Recognition, Psychology, Single-Blind Method, Synaptophysin |
Abstract | 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 potentiation (LTP) in the CA1 region that was completely blunted in CHI control mice. However, DCS did not improve CHI-induced impairment in synaptic glutamate 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. |
DOI | 10.1096/fj.06-7856com |
Alternate Journal | FASEB J |
PubMed ID | 17351125 |
Grant List | R01 NS 050285-01 A2 / NS / NINDS NIH HHS / United States |