Newswise — In a new study by Weill Cornell Medicine at the Burke Neurological Institute (BNI), activation of MAP2K signaling by genetic engineering or repetitive non-invasive transcranial magnetic stimulation (rTMS) can regulate the spinal retrocorticospinal tract (CST) axis. It was found to promote cord sprouting and functional regeneration. Spinal cord injury (SCI) in mice. rTMS is a non-invasive technique that induces electric fields in brain tissue via electromagnetic induction. Although there is increasing evidence to suggest that application of rTMS to the motor cortex may be beneficial for functional recovery in patients with SCI, the molecular and cellular mechanisms underlying the beneficial effects of rTMS remain unclear. This research science translation medicine have shown that high-frequency rTMS (HF-rTMS) activates MAP2K signaling and promotes axonal regeneration and functional recovery, suggesting that rTMS may be a valuable therapeutic option for patients with SCI. increase.
Promoting axonal regeneration in the injured central nervous system (CNS) remains a challenging task. The inability of mature CNS neurons to activate cell-intrinsic growth mechanisms and regenerate damaged axons significantly hinders the development of effective new therapies after traumatic brain or spinal cord injury.
The RAF – mitogen-activated protein kinase kinase (MAP2K, also known as MEK) signaling cascade mediates long-distance axonal outgrowth in developing PNS and CNS neurons. Based on previous findings, BNI investigators believe that RAF signaling regulates an intrinsic axonal growth program, activation of which enables regrowth of adult mammalian CNS axons after his SCI. I hypothesized that there is. They show that the conditional expression of constitutively kinase-activated BRAF in mature corticospinal neurons (CSNs) leads to the expression of a series of transcription factors previously implicated in axonal regeneration in zebrafish retinal ganglion cells. was found to induce Moreover, conditional BRAF activation in the CSN enabled He CST axonal sprouting and regeneration in various experimental models of His SCI in mice. According to her BNI postdoctoral fellow, Xiaofei Guan, MD, PhD, who conducted the experiment, her newly sprouted CST axons synapse with local spinal circuits, further restoring motor function. Improved.
Although rTMS has emerged as a promising strategy to enhance recovery in patients with spinal cord or brain injuries, the plasticity mechanisms underlying these approaches and their full therapeutic potential remain unclear. The BNI research team found that a course of daily high-frequency rTMS sessions activated her MAP2K signaling, regulating the expression of a set of regeneration-associated transcription factors in the same way as genetic BRAF activation. Endogenous MAP2K activity was required for enhanced her CST sprouting, regeneration, and functional recovery in SCI model mice treated with HF-rTMS.
The researchers believe that these results collectively point to a central role for MAP2K signaling in enhancing the growth potential of mature CSNs, suggesting that HF-rTMS may regulate MAP2K signaling by It has been suggested that it may treat spinal cord injuries. The BNI team has initiated a clinical trial testing the HF-rTMS protocol in a healthy subject and her SCI patient. If successful, HF-rTMS could be a noninvasive way to promote axonal regeneration alone or in combination with other additional interventions for SCI or other individuals who may benefit from CNS circuit repair. could emerge as a more targeted, lower-risk treatment option.
This work was supported by grants from the National Institutes of Health, the New York State Health Spinal Cord Injury Research Board, the Craig H. Nielsen Foundation, the Wings for Life Research Foundation, the Goldsmiths Research Foundation, and the Burke Foundation.
About the Burke Institute for Neurology
The Burke Neurological Institute, based in White Plains, New York, was founded in 1978 by Dr. Fletcher McDowell as a research institute dedicated to finding cures for chronic neurological disorders. The Institute translates groundbreaking research into clinical treatments, helping people see, talk and walk again. Their goal is to combine the most rigorous and modern brain science with heartfelt and compassionate care to develop new therapies for stable disability in people suffering from neurological conditions such as stroke, traumatic brain injury and spinal cord injury. To innovate and develop therapeutics. The Burke Neurological Institute is an academic affiliate of Weill Cornell Medicine.
