Inhibition of the Na+ -K+ -2Cl- -cotransporter in choroid plexus attenuates traumatic brain injury-induced brain edema and neuronal damage.
The present study was aimed to elucidate the possible role of Na+ -K+ -2Cl- -cotransporter (NKCC1) on traumatic brain injury-induced brain edema, cerebral contusion and neuronal death by using traumatic brain injury animal model. Contusion volume was verified by 2,3,5,-triphenyltetrazolium chloride monohydrate staining. NKCC1 mRNA expression was detected by RT-PCR and the protein expression of NKCC1 was measured by Western blot. We found that the expression of NKCC1 RNA and protein were up-regulated in choroid plexus apical membrane from 2 h after traumatic brain injury, peaked at 8 h, and lasted for 24 h. Rats in the experimental group displayed severe brain edema (water content: 81.45 +/- 0.32% compared with 78.38 +/- 0.62% of sham group) and contusion volume significantly increased 8 h after traumatic brain injury (864.14 +/- 28.07 mm3). Administration of the NKCC1 inhibitor bumetanide (15 mg/kg, I.V.) significantly attenuated the contusion volume (464.03 +/- 23.62 mm3) and brain edema (water content: 79.12 +/- 0.28%) after traumatic brain injury. Our study demonstrates that NKCC1 contributes to traumatic brain injury-induced brain edema and neuronal damage.
Lu
Kwok-Tung
KT
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
Wu
Chang-Yen
CY
Cheng
Nai-Chi
NC
Wo
Yu-Yuan Peter
YY
Yang
Jen-Tsung
JT
Yen
Hao-Han
HH
Yang
Yi-Ling
YL
D000818:Animals; D001929:Brain Edema / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002034:Bumetanide / Q000494:pharmacology*; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004232:Diuretics / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology*; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis; D064506:Solute Carrier Family 12, Member 2
D004232:Diuretics; D018696:Neuroprotective Agents; C578879:Slc12a2 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D012313:RNA