Excess ammonia in the blood can cause neurologic dysfunction and seizures. Although previous studies have suggested astrocyte swelling and brain edema are associated with hyperammonemia, the authors show that ammonia compromises potassium buffering by astrocytes, increasing extracellular potassium concentrations and resulting in cortical disinhibition. Pharmacological or genetic inhibition of NKCC1 attenuates ammonia-induced neurologic impairment and seizures, suggesting hyperammonemia may be treated by targeting NKCC1.
- Vinita Rangroo Thrane
- Alexander S Thrane
- Maiken Nedergaard
