PMID- 18699862
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20211020
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 107
IP  - 3
DP  - 2008 Nov
TI  - Ischemic insult to cerebellar Purkinje cells causes diminished GABAA receptor 
      function and allopregnanolone neuroprotection is associated with GABAA receptor 
      stabilization.
PG  - 668-78
LID - 10.1111/j.1471-4159.2008.05617.x [doi]
AB  - Cerebellar Purkinje cells (PC) are particularly vulnerable to ischemic injury and 
      excitotoxicity, although the molecular basis of this sensitivity remains unclear. 
      We tested the hypothesis that ischemia causes rapid down-regulation of GABA(A) 
      receptors in cerebellar PC, thereby increasing susceptibility to excitotoxicity. 
      Oxygen-glucose deprivation (OGD) caused a decline in functional GABA(A) 
      receptors, within the first hour of re-oxygenation. Decreased amplitude of 
      miniature inhibitory post-synaptic potentials confirmed that OGD caused a 
      significant decrease in functional synaptic GABA(A) receptors and quantitative 
      Western blot analysis demonstrated the loss of GABA(A) receptor current was 
      associated with a decline in total receptor protein. Interestingly, the potent 
      neuroprotectant allopregnanolone (ALLO) prevented the decline in GABA(A) receptor 
      current and protein. Consistent with our in vitro data, global ischemia in mice 
      caused a significant decline in total cerebellar GABA(A) receptor protein and PC 
      specific immunoreactivity. Moreover, ALLO provided strong protection of PC and 
      prevented ischemia-induced decline in GABA(A) receptor protein. Our findings 
      indicate that ischemia causes a rapid and sustained loss of GABA(A) receptors in 
      PC, whereas ALLO prevents the decline in GABA(A) receptors and protects against 
      ischemia-induced damage. Thus, interventions which prevent ischemia-induced 
      decline in GABA(A) receptors may represent a novel neuroprotective strategy.
FAU - Kelley, Melissa H
AU  - Kelley MH
AD  - Department of Anesthesiology and Peri-Operative Medicine, Oregon Health & Science 
      University, Portland, Oregon 97201, USA.
FAU - Taguchi, Noriko
AU  - Taguchi N
FAU - Ardeshiri, Ardalan
AU  - Ardeshiri A
FAU - Kuroiwa, Masayuki
AU  - Kuroiwa M
FAU - Hurn, Patricia D
AU  - Hurn PD
FAU - Traystman, Richard J
AU  - Traystman RJ
FAU - Herson, Paco S
AU  - Herson PS
LA  - eng
GR  - R21 NS052591/NS/NINDS NIH HHS/United States
GR  - R01 NS058792/NS/NINDS NIH HHS/United States
GR  - T332NS007466-09/NS/NINDS NIH HHS/United States
GR  - T32 NS007466/NS/NINDS NIH HHS/United States
GR  - R21NS052591/NS/NINDS NIH HHS/United States
GR  - R01 NS058792-02/NS/NINDS NIH HHS/United States
GR  - R01NS058792/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080918
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, GABA-A)
RN  - BXO86P3XXW (Pregnanolone)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain Ischemia/*metabolism
MH  - Immunohistochemistry
MH  - Inhibitory Postsynaptic Potentials/drug effects/physiology
MH  - Mice
MH  - Neuroprotective Agents/*pharmacology
MH  - Patch-Clamp Techniques
MH  - Pregnanolone/*pharmacology
MH  - Purkinje Cells/drug effects/*metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-A/drug effects/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2692389
MID - NIHMS70501
EDAT- 2008/08/14 09:00
MHDA- 2008/12/17 09:00
PMCR- 2009/11/01
CRDT- 2008/08/14 09:00
PHST- 2008/08/14 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/08/14 09:00 [entrez]
PHST- 2009/11/01 00:00 [pmc-release]
AID - JNC5617 [pii]
AID - 10.1111/j.1471-4159.2008.05617.x [doi]
PST - ppublish
SO  - J Neurochem. 2008 Nov;107(3):668-78. doi: 10.1111/j.1471-4159.2008.05617.x. Epub 
      2008 Sep 18.