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TBI survivors are presently treated with extensive physical and cognitive rehabilitation, accompanied by medications that may alleviate symptoms yet do not stop or slow neurodegeneration. Recently, researchers have discovered for the first time this process can be pharmacologically reversed in an animal model of this chronic health condition. Thus, offering significant proof of principle in the field and a likely path to a new therapy.

Traumatic brain injury (TBI) is a fundamental cause of cognitive weakening, affecting millions worldwide. Despite growing awareness about TBI's debilitating and lifelong progressive consequences, there are currently no treatments that slow the deteriorative process. TBI survivors are presently treated with extensive physical and cognitive rehabilitation, accompanied by drugs that may alleviate symptoms yet do not halt or slow neurodegeneration. TBI can lead to lifetime detrimental effects on multiple aspects of health.

 Adverse long-term outcomes of TBI commonly include cognitive dysfunction, sensorimotor impairment, or emotional dysregulation, such as depression and anxiety, including deteriorated post-traumatic stress disorder (PTSD). In addition, TBI dramatically increases the risk of later developing age-related forms of dementia, such as Parkinson's and Alzheimer's.

Dr. Pieper and his team examined if it was possible to reverse the lifelong chronic neurodegeneration and related cognitive deficits after TBI, which had never been demonstrated before. 

The study utilized a mouse model that mirrored concussive impact in middle-aged people suffering a TBI decades prior and administered an energy-boosting neuroprotective compound known as P7C3-A20. This had formerly been shown to have practical value in acute TBI. The research team waited one year after injury and gave the combination daily to mice for one month.

Surprisingly, this short-term treatment with P7C3-A20 restored normal cognitive function. The mice were kept under observation for an additional four months, during which time they were not administered any more compounds. Remarkably, the mice still showed normal cognitive function at the end of this period. Thus, cognitive function continued to improve four months later after just one month of treatment.

When the brains were examined under the microscope, we saw that chronic neurodegeneration after TBI had stopped entirely in the mice that had been briefly treated with P7C3-A20. Under electron microscopy, it was discovered that P7C3-A20 had also enabled the repair of the endothelial cells lining the brain's blood vessels.

This is the first time that P7C3-A20 can protect endothelial cells at the interface of the cardiovascular system, and the brain was in the neurovascular unit (NVU). Weakening of the NVU occurs in almost all types of brain injury and brain diseases. It is also a well-known early and chronic indicator of Alzheimer's disease. The team showed that P7C3-A20 directly protects human brain microvascular endothelial cells cultured in the laboratory as well.

TBI is the most significant risk factor for developing Alzheimer's disease, except for aging and genetics. We speculate that preserving the blood-brain barrier might be a way to protect TBI patients from this increased risk.

Currently, no medicines are accessible to patients that protect the blood-brain barrier directly. A prescription with a property, such as one resulting from the P7C3 series of compounds, would have wide-ranging applicability to several conditions of the brain, including TBI and Alzheimer's disease.