The use of probucol, a cholesterol-lowering drug, in mice with traumatic brain injury has been shown to promote neuroregeneration and improve functional deficits, suggesting it could be used to treat humans with brain injuries, a National Health Research Institutes (NHRI) research team said yesterday.
NHRI vice president Chen Wei-jen (陳為堅) said that traumatic brain injuries are usually caused by a severe blow to the head, such as in motor vehicle crashes, falls or being struck by an object.
About 650,000 cases of traumatic brain injury are reported each year in Taiwan, with about 100,000 classified as moderate to severe, Chen said.
Photo: CNA
Survivors of moderate-to-severe traumatic brain injury often have damaged neurological and cognitive functions, as well as other prolonged or permanent disabilities, and are at a higher risk of developing dementia, he said.
However, no drug has been approved to treat that alone.
A research team led by NHRI Institute of Cellular and System Medicine researcher Yet Shaw-fang (林秀芳) found that the daily administration of probucol in mice with traumatic brain injury promoted neuroregeneration, reduced their brain lesion volume, improved motor functions and attenuated memory dysfunctions.
The condition of about 26 percent of people with moderate-to-severe traumatic brain injury who undergo rehabilitation for five years might improve, 22 percent might remain the same, 30 percent might worsen and 22 percent might die, NHRI Institute of Cellular and System Medicine postdoctoral fellow Chen Chien-mei (陳倩玫) said, citing clinical data.
In adults, neurogenesis (the growth of new brain cells) and neuroplasticity (the brain’s capacity to change and adapt) appear to be considerably more limited, so dead or damaged neurons in the brain due to traumatic brain injury usually only have a minimal or partial and slow functional recovery, she said.
As probucol is a compound with anti-oxidant and anti-inflammatory properties, the team administered it to mice with traumatic brain injury in experiments, she said, adding that they surprisingly discovered that probucol activated the brain-derived neurotrophic factor, promoted post-traumatic neurogenesis and neuroplasticity, stimulated neurite outgrowth and reduced brain lesion volume by 33 percent.
Probucol also enhanced recovery from injury-induced body asymmetry, improved post-injury motor function and ameliorated memory dysfunction in the mice, she said, adding that it might also be used to reduce the risk of dementia in people with traumatic brain injury.
The cholesterol-lowering drug has established safety profiles, meaning that it could be repositioned to treat people with traumatic brain injury, Yet said.
As the team has identified the neuroregenerative properties of probucol in mice, as well as its properties in improving post-injury neurological and cognitive disabilities, the findings could be applied to clinical trials to establish the proper dosage and course of treatment for humans, Yet said.
The team’s findings were published in the British Journal of Pharmacology in June.
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