PMID- 17351125
OWN - NLM
STAT- MEDLINE
DCOM- 20070815
LR  - 20220330
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 21
IP  - 9
DP  - 2007 Jul
TI  - D-cycloserine improves functional recovery and reinstates long-term potentiation 
      (LTP) in a mouse model of closed head injury.
PG  - 2033-41
AB  - 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.
FAU - Yaka, Rami
AU  - Yaka R
AD  - Department of Pharmacology, School of Pharmacy, The Hebrew University of 
      Jerusalem, POB 12065, Jerusalem 91120, Israel. yaka@md.huji.ac.il
FAU - Biegon, Anat
AU  - Biegon A
FAU - Grigoriadis, Nikolaos
AU  - Grigoriadis N
FAU - Simeonidou, Constantina
AU  - Simeonidou C
FAU - Grigoriadis, Savvas
AU  - Grigoriadis S
FAU - Alexandrovich, Alexander G
AU  - Alexandrovich AG
FAU - Matzner, Henri
AU  - Matzner H
FAU - Schumann, Johanna
AU  - Schumann J
FAU - Trembovler, Victoria
AU  - Trembovler V
FAU - Tsenter, Jeanna
AU  - Tsenter J
FAU - Shohami, Esther
AU  - Shohami E
LA  - eng
GR  - R01 NS 050285-01 A2/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070309
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Synaptophysin)
RN  - 95IK5KI84Z (Cycloserine)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism/pathology
MH  - Brain Injuries/*drug therapy/etiology/physiopathology
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/genetics
MH  - Cycloserine/pharmacology/*therapeutic use
MH  - Drug Evaluation, Preclinical
MH  - Excitatory Amino Acid Agonists/pharmacology/*therapeutic use
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Head Injuries, Closed/*complications
MH  - Hippocampus/drug effects/physiopathology/ultrastructure
MH  - Long-Term Potentiation/*drug effects
MH  - Male
MH  - Mice
MH  - Microglia/metabolism/pathology
MH  - Motor Activity/drug effects
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Receptors, N-Methyl-D-Aspartate/*agonists/physiology
MH  - Recognition, Psychology/drug effects
MH  - Single-Blind Method
MH  - Synaptophysin/biosynthesis/genetics
EDAT- 2007/03/14 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/03/14 09:00
PHST- 2007/03/14 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/03/14 09:00 [entrez]
AID - fj.06-7856com [pii]
AID - 10.1096/fj.06-7856com [doi]
PST - ppublish
SO  - FASEB J. 2007 Jul;21(9):2033-41. doi: 10.1096/fj.06-7856com. Epub 2007 Mar 9.