AsianScientist (Jul. 13, 2015) – Researchers at the Hong Kong University of Science and Technology (HKUST) have found a way to stimulate the growth of axons, which may spell the dawn of a new beginning for chronic spinal cord injury treatments. Their results have been published in The Journal of Neuroscience.
Chronic spinal cord injury is a formidable hurdle that prevents a large number of injured axons from crossing the lesion, particularly the corticospinal tract (CST). Patients inflicted with spinal cord injury often suffer a loss of mobility or paralysis, which dramatically interferes with the activities of daily life. While physical therapy and rehabilitation would help the patients to cope with the aftermath, axonal regrowth potential of injured neurons was thought to be intractable.
In the present study, researchers report that the deletion of the PTEN gene would enhance compensatory sprouting of uninjured CST axons. Furthermore, the deletion up-regulated the activity of another gene, the mammalian target of rapamycin (mTOR), which promoted regeneration of CST axons. Axons transmit information to different neurons, muscles, and glands; as bundles they help make up nerves.
Led by Dr Liu Kai, the study’s senior author and assistant professor in life sciences at HKUST, the research team initiated PTEN deletion on mice after severing the CST. Similar treatment procedures were carried out on a second group four months after severe spinal cord injuries, and a third group after 12 months. The team recorded a regenerative response of CST axons in all three samples—showing that PTEN deletion stimulates CST sprouting and regeneration, even though the injury was sustained a long time ago.
“As one of the long descending tracts controlling voluntary movement, the corticospinal tract (CST) plays an important role for functional recovery after spinal cord injury,” says Liu. “The regeneration of CST has been a major challenge in the field, especially after chronic injuries.”
“Here we developed a strategy to modulate PTEN/mTOR signaling in adult corticospinal motor neurons in the post-injury paradigm. It not only promoted the sprouting of uninjured CST axons, but also enabled the regeneration of injured axons past the lesion in a mouse model of spinal cord injury, even when treatment was delayed up to one year after the original injury.”
“The results considerably extend the window of opportunity for regenerating CST axons severed in spinal cord injuries,” Liu adds.
Compared with acute injury, axons face more barriers to regenerate after chronic SCI. Previously, scientists have shown that axon retraction may further increase the distance that axons need to travel. Extracellular matrices, which become well consolidated around the chronic lesion site, also increase inhibition. Neuronal aging may also add obstacles to regrowth. In light of all of these challenges, it is indeed surprising to find that CST axons can still regenerate after one year.
“It is interesting to find that chronically injured neurons retain the ability to reform tentative synaptic connections,” says Liu. “PTEN inhibition can be targeted on particular neurons, which means that we can apply the procedure specifically on the region of interest as we continue our research.”
The article can be found at: Du et al. (2015) Pten Deletion Promotes Regrowth of Corticospinal Tract Axons One Year after Spinal Cord Injury.
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Source: Hong Kong University of Science and Technology.
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