Gene Therapy May Help Brain Heal From Stroke, Other Injuries


Source: UT Southwestern Medical Center

Summary: Researchers have found a genetic trigger that may improve the brain’s ability to heal from a range of debilitating conditions, from strokes to concussions and spinal cord injuries.


Astrocytes are the star-shaped glial cell of the central nervous system (CNS) which provide structural and metabolic support, regulate neurotransmitter uptake and synaptic transmission, and help maintain the blood-brain barrier. Under pathological conditions such as stroke, epilepsy, traumatic injury and neurodegenerative disorders, the astrocytes become reactive, undergoing a spectrum of phenotypic changes. Researchers from the UT Southwestern Medical Center have found a genetic trigger that may improve the brain’s ability to heal from a range of debilitating conditions, from strokes to concussions and spinal cord injuries. They found that the LZK gene of astrocytes can be turned on to prompt a recovery response called astrogliosis, in which these star-shaped cells proliferate around injured neurons and form a scar. The study findings were published in the journal Cell Reports.

Gene transfer

Genetically modified astrocytes (red) line the lesion border in the injured spinal cord. A new mouse study shows that triggering a gene inside astrocytes activates the star-shaped cells and may improve the brain’s ability to heal from a range of debilitating conditions, from stroke to concussions and spine injuries. Credit: Meifan Amy Chen, Ph.D. UT Southwestern

The research team deleted the LZK gene in astrocytes of one group of injured mice, which decreased the cells’ injury response and resulted in a larger wound on the spinal cord. They overexpressed the gene in other injured mice, which stimulated the cells’ injury response and resulted in a smaller scar. Overexpressing the gene in uninjured mice also activated the astrocytes, confirming LZK as a trigger for astrogliosis. A smaller scar likely aids the healing process by isolating the injured neurons, similar to how isolating a spreading infection can improve recovery. Further study is needed to analyze whether a compact scar tissue indeed improves recovery and how this process affects the neurons’ ability to reform connections with each other.

Lead author, Dr. Meifan Amy Chen said, “It has been a big mystery whether increasing astrocyte reactivity would be beneficial”, “The discovery of LZK as an on switch now offers a molecular tool to answer this question.”


More Information: Meifan Chen et al, “Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS”, Cell Reports (2018). DOI: 10.1016/j.celrep.2018.02.102 


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