Using bumetanide, a diuretic drug already approved by the Food and Drug Administration, researchers at the University of Texas Medical Branch were able to protect excitatory neurons from the damage caused by long-term swelling in spinal cord injuries.
The researchers administered bumetanide to mice with spinal cord injuries, which resulted in improved recovery of locomotor functions that persisted for at least four weeks after the treatment was ended. Choosing an approved drug should streamline the next steps in evaluating the treatment potential.
The study, published in the September issue of Science Translational Medicine, advances the understanding of spinal cord injury and indicates a potential treatment to enhance recovery.
Secondary injuries result from prolonged neuronal swelling caused by the original injury and can lead to neuronal death. The swelling and loss of excitatory neurons, the researchers found, persisted for more than a month. Excitatory neurons pass signals to other neurons, so the death of these cells can have significant consequences for the neurological system that controls movement. Bumetanide is used to reduce edema, which is the retention of fluids in body tissues.
“Historically, it has been believed that all types of central nervous system edema resolve within two weeks post-injury in both rodents and primates,” said Dr. Bo Chen, assistant professor of neurobiology, and one of the authors of the paper. “However, our findings challenge this long-standing assumption, revealing that excitatory neuronal swelling in mice may persist for up to 35 days post-injury.”
Chen said these results open several other avenues for research.
The UTMB research team plans to investigate bumetanide’s effects beyond locomotor capabilities, including urinary functions, a concern for patients with spinal cord injuries. They also plan to look at various types of spinal cord injuries and investigate more effective alternatives to bumetanide.
Other contributing authors include Qiang Li, Alfredo Sandoval, Junkui Shang, Jia Yi Liew, Tiffany Dunn and Melissa Henwood from UTMB, Philip Williams from Washington University in St. Louis School of Medicine, Zhiyun Yang and Junfeng Su from Boston Children's Hospital and Harvard Medical School, and John Moth from Houston Methodist Hospital.
The researchers administered bumetanide to mice with spinal cord injuries, which resulted in improved recovery of locomotor functions that persisted for at least four weeks after the treatment was ended. Choosing an approved drug should streamline the next steps in evaluating the treatment potential.
The study, published in the September issue of Science Translational Medicine, advances the understanding of spinal cord injury and indicates a potential treatment to enhance recovery.
Secondary injuries result from prolonged neuronal swelling caused by the original injury and can lead to neuronal death. The swelling and loss of excitatory neurons, the researchers found, persisted for more than a month. Excitatory neurons pass signals to other neurons, so the death of these cells can have significant consequences for the neurological system that controls movement. Bumetanide is used to reduce edema, which is the retention of fluids in body tissues.
“Historically, it has been believed that all types of central nervous system edema resolve within two weeks post-injury in both rodents and primates,” said Dr. Bo Chen, assistant professor of neurobiology, and one of the authors of the paper. “However, our findings challenge this long-standing assumption, revealing that excitatory neuronal swelling in mice may persist for up to 35 days post-injury.”
Chen said these results open several other avenues for research.
The UTMB research team plans to investigate bumetanide’s effects beyond locomotor capabilities, including urinary functions, a concern for patients with spinal cord injuries. They also plan to look at various types of spinal cord injuries and investigate more effective alternatives to bumetanide.
Other contributing authors include Qiang Li, Alfredo Sandoval, Junkui Shang, Jia Yi Liew, Tiffany Dunn and Melissa Henwood from UTMB, Philip Williams from Washington University in St. Louis School of Medicine, Zhiyun Yang and Junfeng Su from Boston Children's Hospital and Harvard Medical School, and John Moth from Houston Methodist Hospital.