Inhibition of the Na+ -K+ -2Cl- -cotransporter in choroid plexus attenuates traumatic brain injury-induced brain edema and neuronal damage.

Abstract

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.

• Authors: Kwok-Tung Lu, Chang-Yen Wu, Nai-Chi Cheng, Yu-Yuan Peter Wo, Jen-Tsung Yang, Hao-Han Yen, Yi-Ling Yang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 548 Issue 1-3 Pg. 99-105 (Oct 24 2006) ISSN: 0014-2999 [Print] Netherlands
• PMID: 16962576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diuretics
• Neuroprotective Agents
• Slc12a2 protein, rat
• Sodium Potassium Chloride Symporter Inhibitors
• Sodium-Potassium-Chloride Symporters
• Solute Carrier Family 12, Member 2
• Bumetanide
• RNA

Topics

• Animals
• Brain Edema (drug therapy, metabolism, pathology)
• Brain Injuries (drug therapy, metabolism, pathology)
• Bumetanide (pharmacology)
• Choroid Plexus (drug effects, metabolism, pathology)
• Diuretics (pharmacology)
• Male
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• RNA (biosynthesis)
• Rats
• Rats, Wistar
• Sodium Potassium Chloride Symporter Inhibitors (pharmacology)
• Sodium-Potassium-Chloride Symporters (biosynthesis)
• Solute Carrier Family 12, Member 2