2-Carba cyclic phosphatidic acid regulates blood coagulation and fibrinolysis system for repair after brain injury

Misaki Endo; Mari Gotoh; Mari Nakashima; Yuka Kawamoto; Shiho Sakai; Kimiko Murakami-Murofushi; Kei Hashimoto; Yasunori Miyamoto

doi:10.1016/j.brainres.2023.148511

2-Carba cyclic phosphatidic acid regulates blood coagulation and fibrinolysis system for repair after brain injury

Brain Res. 2023 Nov 1:1818:148511. doi: 10.1016/j.brainres.2023.148511. Epub 2023 Jul 26.

Authors

Misaki Endo¹, Mari Gotoh², Mari Nakashima¹, Yuka Kawamoto¹, Shiho Sakai¹, Kimiko Murakami-Murofushi³, Kei Hashimoto⁴, Yasunori Miyamoto⁵

Affiliations

¹ Graduate School of Humanities and Sciences, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan; Institute for Human Life Science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan.
² Institute for Human Life Science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan.
³ Research Division of Human Welfare Science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan.
⁴ Institute for Human Life Science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan; Academic Production, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan. Electronic address: hashimoto.kei@ocha.ac.jp.
⁵ Graduate School of Humanities and Sciences, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan; Institute for Human Life Science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan. Electronic address: miyamoto.yasunori@ocha.ac.jp.

PMID: 37506965
DOI: 10.1016/j.brainres.2023.148511

Abstract

Effective blood coagulation prevents inflammation and neuronal loss after brain injury. 2-Carba-cyclic phosphatidic acid (2ccPA), a biotherapeutic for brain injury, inhibits blood extravasation resulting from blood-brain barrier breakdown. However, the hemostasis mechanism of 2ccPA remains unclear. We determined the effects of 2ccPA-injection on blood coagulation and fibrinolysis using a needle-induced brain injury model. 2ccPA suppressed the expression of platelet degranulation-related genes. Immediately after brain injury, 2ccPA increased CD41⁺ platelet aggregation around the lesions and promoted fibrin aggregation. Additionally, 2ccPA supported fibrinolysis by upregulating plasminogen activator expression. These results suggest the acute effects of 2ccPA on brain hemostasis.

Keywords: Blood coagulation; Cyclic phosphatidic acid; Fibrinolysis; Traumatic brain injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood Coagulation
Brain Injuries* / drug therapy
Fibrinolysis* / physiology
Humans
Phosphatidic Acids / pharmacology

Substances

2-carba-cyclic phosphatidic acid
Phosphatidic Acids