Ait-Aissa to examine pathway for prevention of radiation-induced cognitive dysfunction

Karima Ait-Aissa, PhD, assistant research professor in Cardiovascular Medicine, received a three-year, $231,000 Career Development Award from the American Heart Association (AHA). A member of the lab of Isabella Grumbach, MD, PhD, Ait-Aissa plans to examine the mechanisms that lead to radiation-induced blood-brain barrier damage, a major contributor of cognitive dysfunction.

“As a young investigator, this award is a testament to the exceptional mentorship and institutional support that I have been fortunate to receive at Grumbach Lab and the Department of Internal Medicine,” Ait-Aissa said. “It will provide me with a solid foundation on which to build my emerging, independent research program.”

Delayed cognitive decline occurs in up to 90% of survivors as late as 30 years after cranial radiation therapy. This cognitive decline is attributed to blood-brain barrier leakage, which is the result of long-term injury and defective repair of vascular endothelial cells. Ait-Aissa’s forthcoming research predicts radiation therapy-induced late blood-brain barrier disruption is stimulated by neurovascular cell-free mitochondrial DNA-induced reactive oxygen species production in a feed-forward pathogenic mechanism.

Ait-Aissa’s proposed pathway will provide an explanation for long-standing observations that progressive vascular effects develop even decades after radiation therapy.

“As an extension of this proposed concept, we speculate that suppression of mitochondrial DNA damage, oxidative stress or the blockade of mitochondrial DNA signaling through TLR9 inhibitors targeted to endothelial cells in human subjects after radiation therapy, could emerge as novel treatment approaches in the prevention of cognitive decline in cancer survivors,” Ait-Aissa said.

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