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Lipid molecules help to get stroke therapies into the brain

April 17, 2023
Tokyo Medical and Dental University
Researchers have found that a promising stroke therapy, known as antisense oligonucleotides, is preferentially taken up from the blood into areas of stroke damage in the brain when the molecules are linked to a specific kind of lipid. This therapy can be given relatively late after a stroke occurs, and is hoped to lead to reduced stroke-related disabilities.

To get therapies into the brain after a stroke, researchers are increasingly making use of the blood-brain barrier, which allows only certain molecules to pass from the blood into the brain. In a study published earlier this year in Molecular Therapy, Japanese researchers have found that antisense oligonucleotides -- specialized molecules that can modulate RNA and alter protein production -- are preferentially taken up from the blood into areas of stroke damage when they're linked to a specific kind of lipid known as ?-tocopherol (TOC).

Current stroke therapies are only effective if they are delivered within a short window of time, which limits their effectiveness in many patients. Many new therapies are being investigated that can be applied outside this short window of opportunity. One such therapy involves the use of antisense oligonucleotides, which can be targeted to increase the production of beneficial proteins after a stroke, for example, or to decrease the production of harmful proteins. However, getting these molecules into the right area at the right time can be difficult, something that the researchers at Tokyo Medical and Dental University wanted to address.

"We've recently developed an antisense oligonucleotide known as a DNA/RNA heteroduplex oligonucleotide, or HDO," says senior author of the study Takanori Yokota. "To see how different lipids affect the uptake of HDO in the brain, we linked it to either cholesterol or TOC and then injected it into the blood of mice who had been given an experimentally induced stroke in just one side of the brain."

Unexpectedly, the TOC-linked molecules were observed at very high levels in the stroke-lesioned side of the brain only, whereas the cholesterol-linked molecules were high in both sides of the brain. This suggests that TOC specifically increases HDO uptake after stroke, while cholesterol does not. Furthermore, because HDO can be tailored to target different genes, it was used to silence a gene known to be beneficial in stroke. As expected, the researchers observed greater areas of stroke-related damage in the mice treated with this TOC-linked HDO.

"Together, our findings suggest that TOC-linked HDO is safe to use and is preferentially taken up and incorporated into cells in areas of stroke damage," says Yokota. "This delivery method is potentially very useful for the targeted up- or down-regulation of protein expression after stroke."

Given the relative lack of stroke therapies targeting the pathological processes that happen after a stroke, the current findings are very important. Increasing anti-inflammatory proteins and/or lowering inflammatory proteins in the stroke-lesioned brain is a promising way to avoid secondary damage to the brain after a stroke has occurred, and will lead to reductions in stroke-related disabilities.

Story Source:

Materials provided by Tokyo Medical and Dental University. Note: Content may be edited for style and length.

Journal Reference:

  1. Fuying Li, Keiko Ichinose, Satoru Ishibashi, Syunsuke Yamamoto, Eri Iwasawa, Motohiro Suzuki, Kie Yoshida-Tanaka, Kotaro Yoshioka, Tetsuya Nagata, Hideki Hirabayashi, Kaoru Mogushi, Takanori Yokota. Preferential delivery of lipid-ligand conjugated DNA/RNA heteroduplex oligonucleotide to ischemic brain in hyperacute stage. Molecular Therapy, 2023; 31 (4): 1106 DOI: 10.1016/j.ymthe.2023.01.016

Cite This Page:

Tokyo Medical and Dental University. "Lipid molecules help to get stroke therapies into the brain." ScienceDaily. ScienceDaily, 17 April 2023. <>.
Tokyo Medical and Dental University. (2023, April 17). Lipid molecules help to get stroke therapies into the brain. ScienceDaily. Retrieved May 19, 2024 from
Tokyo Medical and Dental University. "Lipid molecules help to get stroke therapies into the brain." ScienceDaily. (accessed May 19, 2024).

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