Ultrasound induced permeabilization of cell membranes as a therapy for cytotoxic neuronal edema

One of the consequences of ischemic injury to neurons is cytotoxic edema, which has several undesirable consequences including an increase in the intra-cranial pressure. This project tests the hypothesis that pressure gradients induced by ultrasonic waves can be used to permeabilize the cell membrane leading to changes in ionic gradients and an efflux of water reversing the swelling effect. In a N1E mouse neuroblastoma cell culture model of lactacidosis, swelling was induced by lowering the pH of the medium. Flow cytometry measurements indicate dramatic Increased scatter intensity accompanied by an increase in the complexity of the dendritic arbors at pH of 4.0. Upon sonication at 1 MHz and an intensity of 0.1 W/cm/sup 2/ for 3 minutes, the top 30% of scatter intensity values dropped by 18% accompanied by a decrease in complexity and size. In a similar model, swelling was also induced in N2A mouse neuroblastoma where the pH of the medium was dropped to 4.0. Upon sonication at 1 MHz and an intensity of 0.1 W/cm/sup 2/ for 3 minutes a reduction in swelling was imaged captured using a camera and an inverted microscope. In conclusion, ultra-sound induced permeabilization may be a potentially promising approach for treating cytotoxic neuronal edema.