PMID- 12535773
OWN - NLM
STAT- MEDLINE
DCOM- 20030401
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 961
IP  - 1
DP  - 2003 Jan 24
TI  - Inhibition of Na(+)-K(+)-Cl(-) cotransporter during focal cerebral ischemia 
      decreases edema and neuronal damage.
PG  - 22-31
AB  - Our previous study demonstrated that pharmacological inhibition of the 
      Na(+)-K(+)-Cl(-) cotransporter isoform 1 (NKCC1) during ischemia and reperfusion 
      attenuated neuronal damage and edema. In this study, we further investigated 
      whether NKCC1 activity contributes to ischemic damage during either ischemia or 
      reperfusion. Immunoblotting revealed that expression of NKCC1 protein was 
      increased following 2-h focal ischemia in cerebral cortex. A sustained 
      up-regulation of NKCC1 in cortex was detected at 4, 8, 12, and 24 h of 
      reperfusion. An increase in the phosphorylated NKCC1 (NKCC1-p) was found at 4 and 
      8 h of reperfusion. In striatum, a significant increase in NKCC1 expression 
      occurred between 4 and 24 h of reperfusion and no elevation of NKCC1-p signal was 
      observed. Artificial cerebral spinal fluid (aCSF) or 100 microM bumetanide in 
      aCSF were continuously microdialyzed into left cortices either 1 h prior to 
      ischemia plus 2-h ischemia, or only during 24-h reperfusion. Infarction volume 
      was significantly decreased in the pre-ischemic bumetanide-treated group (P<0.05) 
      but not in the post-ischemic treatment group (P>0.05). In addition, pre-ischemic 
      bumetanide treatment reduced the ipsilateral water content increase by 70% 
      (P<0.05). Inhibition of NKCC1 did not attenuate poly (ADP-ribose) polymerase 
      cleavage or the number of TUNEL-labeled apoptotic cells in ischemic brains. These 
      results suggest that inhibition of NKCC1 attenuates cytotoxic edema and necrotic 
      neuronal death during focal ischemia. Activation of NKCC1 activity plays a role 
      in the early stage of ischemic damage.
FAU - Yan, Yiping
AU  - Yan Y
AD  - Department of Neurological Surgery, University of Wisconsin Medical School, 
      Madison, WI 53792, USA.
FAU - Dempsey, Robert J
AU  - Dempsey RJ
FAU - Flemmer, Andreas
AU  - Flemmer A
FAU - Forbush, Biff
AU  - Forbush B
FAU - Sun, Dandan
AU  - Sun D
LA  - eng
GR  - R01DK47662/DK/NIDDK NIH HHS/United States
GR  - R01NS38118/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Slc12a2 protein, rat)
RN  - 0 (Sodium Potassium Chloride Symporter Inhibitors)
RN  - 0 (Sodium-Potassium-Chloride Symporters)
RN  - 0 (Solute Carrier Family 12, Member 2)
RN  - 0Y2S3XUQ5H (Bumetanide)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/pathology
MH  - Brain Edema/*etiology/*pathology
MH  - Brain Ischemia/*complications/*metabolism
MH  - Bumetanide/administration & dosage/pharmacology
MH  - Cerebral Infarction/pathology
MH  - Drug Administration Schedule
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Membrane Glycoproteins/chemistry
MH  - Neurons/*pathology
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Sodium Potassium Chloride Symporter Inhibitors
MH  - Sodium-Potassium-Chloride Symporters/*metabolism
MH  - Solute Carrier Family 12, Member 2
EDAT- 2003/01/22 04:00
MHDA- 2003/04/02 05:00
CRDT- 2003/01/22 04:00
PHST- 2003/01/22 04:00 [pubmed]
PHST- 2003/04/02 05:00 [medline]
PHST- 2003/01/22 04:00 [entrez]
AID - S0006899302038325 [pii]
AID - 10.1016/s0006-8993(02)03832-5 [doi]
PST - ppublish
SO  - Brain Res. 2003 Jan 24;961(1):22-31. doi: 10.1016/s0006-8993(02)03832-5.