Poster Presentation 2014 International Biophysics Congress

Potential action of low intensity ultrasound on iGluRs and AQP4 membrane localization to inhibit brain edema formation in rats (#294)

Mrigendra Bir Karmacharya 1 , Kil Hwan Kim 1 , Byoung-Hyun Min 2 , So Ra Park 1 , Byung Hyune Choi 3
  1. Department of Physiology, Inha University College of Medicine, Incheon, South Korea
  2. Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon, South Korea
  3. Department of Biomedical Sciences, Inha University College of Medicine, Incheon, South Korea

Brain edema is a pathological condition where there is a net increase in the brain water content, the brain tissue volume and intracranial pressure consequently causing brain herniation, irreversible brain damage, and ultimately, death. It is a major contributing factor to morbidity and mortality of a wide variety of nervous system disorders. In this study, we examined whether low intensity ultrasound (LIUS) can inhibit brain edema formation in rat model in vitro. Cytotoxic edema was induced in the rat hippocampal slices by incubation in oxygen glucose deprivation (OGD) condition or glutamate. We found that both the OGD and glutamate treatment induced edema, and that the LIUS stimulation attenuated edema formation in the hippocampal slices. To understand further the underlying mechanism of LIUS action on brain edema, we examined whether ionotropic (i) or metabotropic (m) glutamate receptors (GluR) are involved during glutamate induced edema. Our results show that the hippocampal slices incubated with 300 or 500 μM NMDA, an iGluR agonist, but not DHPG, an mGluR agonist, have significantly higher water content than the non-treated group. Furthermore, treatment with 50 or 100 μM ketamine, an iGluR antagonist, inhibited the edema formation. Interestingly, we found that LIUS inhibited NMDA-induced edema formation in vitro. As water channel protein aquaporin 4 (AQP4) has been implicated in brain edema formation, we asked whether the lowering of water content in the LIUS stimulated slices is also related with AQP4. We found that the membrane localization of AQP4 in the astrocytic foot processes was increased in the edematous hippocampal slices, but was decreased in the LIUS-stimulated slices. Our data, thus, suggest that LIUS stimulation attenuated cytotoxic brain edema formation in vitro and it possibly involved inactivation of iGluRs and their downstream signaling pathways which subsequently resulted in a decreased activation and a lesser membrane localization of AQP4.