Understanding Ultrasounds Editing Of Gene Expression

The blood brain barrier is an extremely selective semipermeable mmembrane which separates the blood that circulates in the body from the fluids that exist in the brain. Despite being excellent at preventing various neurotoxins and blood based diseases from infiltrating the brain, it manages to become a hindrance when it comes to administering drugs which want to directly effect the brain. This is one of the reasons that central nervous system diseases are so difficult to cure. One of the methods that has been employed for over fifteen years is to administer focused ultrasound which can work with induced microbubbles circulating in the body to increase the permeability of the blood brain barrier.

Although we are certain this process works, as it has been shown to be effective on human patients multiple times, we are still unsure about what the side effects of sonification might be. This study is the first performed on living beings to see what effects the ultrasound has on the genetic and inscriptional level for a day after the administration. Twelve male rats were taken and injected with the relevant anaesthesia. The animals then had to be imobalised as the ultrasound was targeted at their heads. Changes in the gene expression was analysed six and twenty four hours after the sound was first applied. Of the 19105 genes that were analysed, 60 were upregulated (increased production) after six hours and 109 were downregulated. After twenty fours hours these numbers had significantly changed with 101 genes being upregulated and only 8 being downregulated. Obviously the control group of “sham animals” didn’t display any change. There was a notable trend for the upregulated genes at six hours to be those related to an anti-inflammatory response but many of these genes returned to normal expression after twenty four hours. The same is basically true of transporter genes and downregulation, with many of the first downregulated being associated with transport mechanism but then returning to normal later. Overall as these genetic altering were minimal and only for a short period the method of focused ultrasound should be viewed as safe. There is still work to be done on possible long term effects but for the moment it offers one of the best methods for neurological drug delivery.

Paper links: Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome


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