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Savita Khanna, PhD

Award Name Pilot Grant


Glutamate in Brain Injury; Neurotoxin to Neuroprotectant

The Ohio State University Center for Clinical and Translational Science has awarded Savita Khanna, PhD, a pilot grant for her research involving the role of glutamate in brain injury.

Khanna’s research focuses on examining how supplemental oxygen therapy can protect neurons during stroke and other brain trauma.

“We want to know how important oxygen starvation, or hypoxia, is as an insult that contributes to stroke-induced neuronal death,” Khanna said.

During stroke, blood vessels in the brain are blocked and blood-borne products, such as oxygen and glucose, are not able to get to the brain. The brain releases excessive amounts of the neurotransmitter glutamate, which damages brain tissue.

Khanna’s past research has shown that oxygen therapy provided during stroke can correct stroke-induced oxygen deficiency and protect brain tissue. Animals receiving oxygen therapy demonstrated signs of increased glutamate metabolism during stroke.

Her new research addresses whether the glutamate released during stroke can be used as a source of energy when supplemental oxygen is applied.

For the brain to function normally, it needs oxygen and glucose to make energy. Khanna theorizes that if the brain has sufficient oxygen during brain trauma, it might use glutamate in place of glucose.

In the Journal of Cerebral Blood Flow and Metabolism, Khanna reported a reduction in brain damage when oxygen therapy was given during stroke-induced hypoxia. However, when oxygen therapy was applied after removing the blockage and blood flow was restored, damage was more severe. Khanna said this pointed to a limited therapeutic window of opportunity for oxygen therapy.

Since current treatment for stroke includes the administration of medication that dissolves clots, this will be important in clinical translation.

Khanna is now working to determine the mechanism behind her findings. She wants to identify whether glutamate, a known neurotoxin, can transform into an energy source for the brain when oxygen therapy is applied during stroke.

In rodent models, strokes are induced and oxygen therapy is given. MRIs of the brain following stroke are used to evaluate damage. Khanna is also working with cells in culture, to establish the conditions needed for glutamate to be used as an energy source.

Khanna said the treatment is easily translatable, because giving 100 percent oxygen to stroke patients is simple and quick.

“If proven beneficial, oxygen therapy can easily transition to a clinical setting without excessive cost to heath care,” Khanna said.

With resources provided by the OSU CCTS award, Khanna is working to strengthen her preliminary findings to move toward a National Institutes of Health proposal in hope of developing therapeutic oxygen strategies targeted to address metabolic damage in stroke.

By Emily Tramte, Friday, May 28, 2010

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