Interaction of aquaporin ۴ and N-methyl-D-aspartate NMDA receptor ۱ in traumatic brain injury of rats

Objective(s): -methyl-D-aspartate NMDA receptor (NMDAR) and aquaporin ۴ (AQP۴) are involved in the molecular cascade of edema after traumatic brain injury (TBI) and are potential targets of studies in pharmacology and medicine. However, their association and interactions are still unknown.Materials and Methods: We established a rat TBI model in this study. The cellular distribution patterns of AQP۴ after inhibition of NMDAR were determined by Western blotting and immunoreactive staining. Furthermore, the regulation of NMDA receptor ۱ by AQP۴ was studied by injection of a viral vector targeting AQP۴ by RNAi into the rat brain before TBI.Results: The results suggest that AQP۴ protein expression increased significantly (P<۰.۰۵) after TBI and was down-regulated by the NMDAR inhibitor MK۸۰۱. This decrease could be partly reversed using the NMDAR agonist NMDA. This indicated that AQP۴ mRNA levels and protein expression are regulated by the NMDA signaling pathway. By injection of AQP۴ RNAi viral vector into the brain of TBI rat models, we found that the mRNA and protein levels of NMDAR decreased significantly (P<۰.۰۵). This suggested that NMDAR is also regulated by AQP۴.Conclusion: These data suggested that the inhibition of AQP۴ down-regulates NMDAR expression, which might be one of the mechanisms involved in edema after TBI.

Keywords:

Aquaporin ۴ , Edema , N-methyl-D-aspartate , NMDA receptor , NMDAR۱ , Traumatic brain injury