PMID- 9594256
OWN - NLM
STAT- MEDLINE
DCOM- 19980602
LR  - 20061115
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 110
IP  - 8
DP  - 1997 Aug
TI  - Effects of antisense oligodeoxynucleotides to NR1 on suppression of seizures and 
      protection of cortical neurons from excitotoxicity in vivo and in vitro.
PG  - 579-83
AB  - OBJECTIVE: To investigate the effects of NR1 subunit on the initiation and 
      development of seizures and protection of cortical neurons from excitotoxicity by 
      using antisense oligodeoxynucleotides (ODN) to NR1 in vivo and in vitro. METHODS: 
      Intracerebroventricular injection, temporal cortex slices discharge, cerebral 
      cortical neuronal culture, induction of neurotoxicity and [3H]MK-801 binding were 
      used in this study. RESULTS: After an antisense ODN for NR1 was administered 
      intracerebroventricularly (i.c.v. 100 micrograms in 10 microliters) once daily, 
      for three days in genetically epilepsy-prone rats (GEPR, P77PMC), the animals did 
      not develop any clonic and tonic convulsions and their seizure scores were 
      significantly lower compared to the control groups. The frequency and amplitude 
      of early seizure-like events (SLEs) and late recurrent discharges (LRD), induced 
      by lowering Mg2+, were reduced in entorhinal cortex (EC) of the temporal slice 
      treated by antisense ODNs. Pretreatment with antisense ODN (2 microM) protected 
      more than 52% of glutamate-sensitive neurons and reduced the [3H]MK-801 binding 
      to 50% in cultured cerebral cortical neurons. CONCLUSIONS: 
      N-methy-D-aspartate-receptors (NMDAR), specifically the NR1 subunit, may 
      participate and play important roles in the initiation and propagation of 
      epilepsy in the P77PMC rat.
FAU - Shan, W
AU  - Shan W
AD  - Department of Pediatrics, First Teaching Hospital, Beijing Medical University, 
      China.
FAU - Wu, X
AU  - Wu X
FAU - Zhang, G
AU  - Zhang G
FAU - Zhang, Y
AU  - Zhang Y
FAU - Liang, Y
AU  - Liang Y
FAU - Wang, Z
AU  - Wang Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Excitatory Amino Acids)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Down-Regulation
MH  - Epilepsy/pathology/*prevention & control
MH  - Excitatory Amino Acids/metabolism
MH  - Neurons/pathology
MH  - Oligonucleotides, Antisense/*pharmacology
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/classification/drug effects/*metabolism
MH  - Temporal Lobe/physiopathology
EDAT- 1997/08/01 00:00
MHDA- 1998/05/22 00:01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1998/05/22 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
PST - ppublish
SO  - Chin Med J (Engl). 1997 Aug;110(8):579-83.