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martyb writes:

'Cell Pores' Discovery Gives Hope to Millions of Brain and Spinal Cord Injury Patients:

Scientists have discovered a new treatment to dramatically reduce swelling after brain and spinal cord injuries, offering hope to 75 million victims worldwide each year.

[...] The researchers used an already-licensed anti-psychotic medicine -- trifluoperazine (TFP) -- to alter the behaviour of tiny water channel 'pores' in cells known as aquaporins.

Testing the treatment on injured rats, they found those animals given a single dose of the drug at the trauma site recovered full movement and sensitivity in as little as two weeks, compared to an untreated group that continued to show motor and sensory impairment beyond six weeks after the injury.

The treatment works by counteracting the cells' normal reaction to a loss of oxygen in the CNS -- the brain and spinal cord -- caused by trauma. Under such conditions, cells quickly become 'saltier' because of a build-up of ions, causing a rush of water through the aquaporins which makes the cells swell and exerts pressure on the skull and spine. This build-up of pressure damages fragile brain and spinal cord tissues, disrupting the flow of electrical signals from the brain to the body and vice versa.

But the scientists discovered that TFP can stop this from happening. Focusing their efforts on important star-shaped brain and spinal cord cells called astrocytes, they found TFP prevents a protein called calmodulin from binding with the aquaporins. Normally, this binding effect sends the aquaporins shooting to the surface of the cell, letting in more water. By halting this action, the permeability of the cells is reduced.

[...] Since TFP is already licensed for use in humans by the US Federal Drug Administration (FDA) and UK National Institute for Health and Care Excellence (NICE) it could be rapidly deployed as a treatment for brain injuries. But the researchers stressed that further work would allow them to develop new, even better medicines based on their understanding of TFP's properties.

[...] According to the World Health Organisation (WHO), each year around 60 million people sustain a traumatic brain or spinal cord injury and a further 15 million people suffer a stroke. These injuries can be fatal or lead to long-term disability, psychiatric disorders, substance abuse or self-harm.

Journal Reference:
Philip Kitchen, Mootaz M. Salman, Andrea M. Halsey, et al. Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema. Cell, 2020; 181 (4): 784 DOI: 10.1016/j.cell.2020.03.037

Original Submission