Light-Up Method for Stroke Recovery

One promising method that is being explored to help with stroke recovery is to transplant neural progenitor cells to restore lost functions. However, such a treatment would require the cells to “know” how to integrate into a mature brain. Now, researchers at Emory University School of Medicine have developed a way to nudge the cells onto the right path using light stimulation. This method, which the researchers have named “optochemogenetics” modifies a widely used neuroscience tool to aid in stroke recovery. Results of a study in mice were reported today in the Journal of Neuroscience.

Optogenetics have emerged recently as a useful tool for studying the brain, allowing neuroscientists to activate or inhibit groups of neurons at the flip of a switch. Generally, the technique involves hooking fiber optic cables to the heads of mice, but the Emory team sought to remove the cables so they could modify the technique for stroke recovery.

The key to this modification were engineered proteins called “luminopsins” designed to be stimulated by light as well as generate their own light when in the presence of a chemical called coelentrerazine (CTZ).

The scientists introduced genes encoding luminopsins into induced pluripotent stem cells, which were then cultured to form neural progenitor cells. The neural progenitor cells were delivered into the brains of mice who had suffered stroke a week prior. CTZ was then provided intranasally twice a day for two weeks. 

Administration of CTZ provided positive benefits including more survival and intact axons, more connections within the brain, better response to electrical stimulation, and recovery of function in affected limbs. When tested on various tasks, CTZ and progenitor cells could restore use of a stroke-affected limb to normal levels in young mice, and provide partial recovery in older animals.

Use of luminopsins offers flexibility in the way neural progenitor cells can be turned on and off—the ability to stimulate with CTZ rather than light could expand the clinical significance of optogenetics. The researchers are also testing their approach for treatment of traumatic brain injury.

Image: Gaussia luciferase (Gluc) is fused to the ChR protein. ChR can be activated by blue light or by light emitted by Gluc when binding to its substrate coelenterazine (CTZ). YFP = yellow fluorescent protein. Image courtesy of Shan Ping Yu.