PMID- 15350643
OWN - NLM
STAT- MEDLINE
DCOM- 20041209
LR  - 20220321
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 128
IP  - 2
DP  - 2004
TI  - Injury-induced alterations in N-methyl-D-aspartate receptor subunit composition 
      contribute to prolonged 45calcium accumulation following lateral fluid 
      percussion.
PG  - 305-22
AB  - Cells that survive traumatic brain injury are exposed to changes in their 
      neurochemical environment. One of these changes is a prolonged (48 h) uptake of 
      calcium which, by itself, is not lethal. The N-methyl-D-aspartate receptor 
      (NMDAR) is responsible for the acute membrane flux of calcium following trauma; 
      however, it is unclear if it is involved in a flux lasting 2 days. We proposed 
      that traumatic brain injury induced a molecular change in the NMDAR by modifying 
      the concentrations of its corresponding subunits (NR1 and NR2). Changing these 
      subunits could result in a receptor being more sensitive to glutamate and prolong 
      its opening, thereby exposing cells to a sustained flux of calcium. To test this 
      hypothesis, adult rats were subjected to a lateral fluid percussion brain injury 
      and the NR1, NR2A and NR2B subunits measured within different regions. Although 
      little change was seen in NR1, both NR2 subunits decreased nearly 50% compared 
      with controls, particularly within the ipsilateral cerebral cortex. This decrease 
      was sustained for 4 days with levels returning to control values by 2 weeks. 
      However, this decrease was not the same for both subunits, resulting in a 
      decrease (over 30%) in the NR2A:NR2B ratio indicating that the NMDAR had 
      temporarily become more sensitive to glutamate and would remain open longer once 
      activated. Combining these regional and temporal findings with 45calcium 
      autoradiographic studies revealed that the degree of change in the subunit ratio 
      corresponded to the extent of calcium accumulation. Finally, utilizing a 
      combination of NMDAR and NR2B-specific antagonists it was determined that as much 
      at 85% of the long term NMDAR-mediated calcium flux occurs through receptors 
      whose subunits favor the NR2B subunit. These data indicate that TBI induces 
      molecular changes within the NMDAR, contributing to the cells' post-injury 
      vulnerability to glutamatergic stimulation.
FAU - Osteen, C L
AU  - Osteen CL
AD  - Brain Injury Research Center, Division of Neurosurgery/Department of Surgery, 
      David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7039, USA.
FAU - Giza, C C
AU  - Giza CC
FAU - Hovda, D A
AU  - Hovda DA
LA  - eng
GR  - NS02197/NS/NINDS NIH HHS/United States
GR  - NS27544/NS/NINDS NIH HHS/United States
GR  - NS30308/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Calcium Radioisotopes)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Fluoresceins)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Organic Chemicals)
RN  - 0 (Piperidines)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (fluoro jade)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - R8OE3P6O5S (ifenprodil)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Autoradiography
MH  - Behavior, Animal/drug effects
MH  - Blotting, Western
MH  - Brain Injuries/*metabolism/pathology/physiopathology/psychology
MH  - Calcium/*metabolism
MH  - Calcium Radioisotopes
MH  - Dizocilpine Maleate/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Fluoresceins
MH  - Fluorescent Dyes
MH  - Male
MH  - Occipital Lobe/metabolism
MH  - Organic Chemicals
MH  - Parietal Lobe/metabolism
MH  - Piperidines/pharmacology
MH  - Protein Isoforms/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Time Factors
MH  - Trauma Severity Indices
MH  - Wounds, Nonpenetrating/*metabolism/pathology/physiopathology/psychology
EDAT- 2004/09/08 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/09/08 05:00
PHST- 2004/06/22 00:00 [accepted]
PHST- 2004/09/08 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/09/08 05:00 [entrez]
AID - S0306-4522(04)00527-5 [pii]
AID - 10.1016/j.neuroscience.2004.06.034 [doi]
PST - ppublish
SO  - Neuroscience. 2004;128(2):305-22. doi: 10.1016/j.neuroscience.2004.06.034.