Xenon therapy shortly after TBI reduces neuronal cell loss and chronic neuroinflammation and improves survival and clinically relevant outcomes, such as long-term cognitive function.
Traumatic Brain Injury (TBI) is the leading cause of death and disability in under 45-year-olds in developed countries. In Europe, about 7.7 million people with disabilities live after TBI (source 1). The primary injury caused by the initial application of force (such as a fall or traffic accident) is followed by secondary damage, which develops in the minutes, hours and days thereafter.
Xenon is a noble gas with neuroprotective properties, which can improve short-term and long-term results after TBI. This is the conclusion of a study published at the end of May 2019 in the British Journal of Anaesthesia in which 72 mice were treated with either xenon (75% Xe: 25% O2) or control gas (75% N2: 25% O2) after controlled traumatic brain damage (sources 2, 3).
Xenon significantly reduced TBI sequelae (p < 0.05), improved short-term vestibulomotor function (p < 0.01), and protected against late TBI-associated memory deficits. It also reduced white matter loss in the contralateral corpus callosum and nerve cell loss in the contralateral hippocampus (both after 20 months).
If a TBI is survived, long-term damage is a major problem. Many patients remain disabled for life and are clearly limited in their ability to work or reintegrate socially. TBI early in life is a risk factor for the development of cognitive dysfunction, Alzheimer's or other neurodegenerative diseases later in life. The risk of death also remains massively increased over years: a long-term observational study calculated a sevenfold increase in the risk of death in 15-54-year-olds after TBI up to 13 years after the event (source 4).
Xenon showed long-term neuroprotective effects in this respect. Treatment was associated with significantly less neuroinflammation in multiple brain areas associated with associative memory (p < 0.05) and lower reactive astrogliosis and microglia proliferation. Also, the survival of xenon-treated mice was significantly improved (p < 0.05 up to 12 months after injury).
There is currently no specific drug therapy available for TBI patients. The treatment is supportive and rehabilitative. Main author Dr. Rita Campos-Pires of the Imperial College London says: "There is currently a large gap in the therapies we can offer TBI patients, which is an injury that can affect all areas of life. Although xenon for TBI has not yet been studied in humans, our results expand the growing body of evidence that it could be used to prevent secondary damage after head trauma."
Xenon is already used in humans for general anesthesia, has few side effects and could easily be given via inhalation or in mechanically ventilated patients in intensive care. Dr. Campos-Pires adds: "Xenon seems to work through a variety of pathways, but one of the most likely mechanisms that could explain the protective effects on brain tissue is the inhibition of NMDA receptors that are overactive after brain injury. On the basis of the good safety profile of xenon and the results of the present study, the researchers hope to be able to investigate the efficacy of xenon in human TBI patients in the future (source 3).
Sources:
1. Tagliaferri, F., Compagnone, C., Korsic, M., Servadei, F. & Kraus, J. A systematic review of brain injury epidemiology in Europe. Acta Neurochir (Wien) 148, 255–268; discussion 268 (2006).
2. Campos-Pires, R. et al. Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice. Br J Anaesth (2019). doi:10.1016/j.bja.2019.02.032
3. Head injury effects halted by xenon gas, finds first-ever life-long study in mice. ScienceDaily Available at: https://www.sciencedaily.com/releases/2019/05/190521075057.htm. (Accessed: 4th June 2019)
4. McMillan, T. M., Teasdale, G. M., Weir, C. J. & Stewart, E. Death after head injury: the 13 year outcome of a case control study. J. Neurol. Neurosurg. Psychiatry 82, 931–935 (2011).