Progesterone: How it may be the Next Best Therapy for Traumatic Brain Injury (TBI)
Traumatic brain injuries, or TBIs, are a detrimental source of serious disability and death, especially in the United States, and little treatment is available today that can effectively battle the mortality rate of TBIs (2024). In fact, as of 2021, there were around 214,110 TBI-related hospitalizations. 69,473 TBIs resulted in death (2024).
Recent findings on the role of progesterone highlight promising results for combatting TBI. Traditionally, progesterone has been studied for its key role in reproductive biology. But progesterone embodies far more properties than supporting menstruation and the early stages of pregnancy– it is also protective against neurodegenerative diseases (Meharvan, 2024). Dr. Meharvan Singh et al. were able to demonstrate progesterone’s protective effects by observing how a TBI responded to administered progesterone using animal models. The team found that cerebral edema was reduced up to 24 hours after the injury. Other neuroprotective mechanisms the team observed included progesterone’s ability to reduce complement factor C3, GFAP (glial fibrillary acidic protein), and nuclear factor kappa beta. More specifically, when there are excessive amounts of complement factor C3, progesterone decreases its levels to prevent inflammation and further damage to the brain (Meharvan, 2024).
So, how might progesterone help combat TBIs? Numerous studies underline that the treatment lies in progesterone and its metabolites– both significantly help the CNS develop and repair following an injury, such as a TBI (Stein, 2011). In their studies, Dr. Donald Stein et al. used mice to test the therapeutic properties of progesterone following an injury to the medial frontal cortex. They found that after 3-5 days of administering progesterone, cerebral edema was dramatically reduced. In addition, they saw improvement in the mice’s spatial learning and sensory performance when compared to the controls of their study (Stein, 2011).
Another example that highlights progesterone's success happened in 2007. Phase II clinical trials were conducted to see the effects of progesterone in treating TBIs. Participants were reported with moderate-to-severe cases of TBI. After they were given progesterone for three days, their mortality rate was reduced by half in comparison to the controls (Stein, 2011). After 30 days of being administered progesterone, functional outcomes were reported. These clinical trials provide promising evidence of progesterone’s ability to reduce inflammation and provide trophic support to damaged nerve cells. What makes progesterone reputable compared to other drugs meant to treat TBI is that it can act at multiple receptor sites in the brain, whereas other competitor drugs can only act at a single or few receptor sites (Stein, 2011). This is what makes progesterone versatile.
What makes progesterone a novel treatment option for TBIs is the many neuroprotective properties it has that other drugs simply do not. To reiterate, many studies demonstrate that it reduces edema and inflammation, helps stimulate neuron repair, and directly enters the blood-brain barrier (Stein, 2011). These effects map progesterone out to be a potential future treatment option for TBIs.
References
Centers for Disease Control and Prevention (2024). TBI Data. Centers for Disease Control and
Prevention. www.cdc.gov/traumatic-brain-injury/data-research/index.html.
Singh, Krishnamoorthy M., V. R. , Kim, Khurana, S., and La Porte, H. M. (2024). Brain-derived
neuerotrophic facto and related mechanisms that mediate and influence
progesterone-induced neuroprotection. Front. Endocrinol. 15:1286066.
doi:10.3389/fendo.2024.1286066.
Stein, D. G. (2011). Is progesterone a worthy candidate as a novel therapy for traumatic brain
injury? Dialogues in Clinical Neuroscience, 13(3), 352–359.
https://doi.org/10.31887/DCNS.2011.13.2/dstein.
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