January 7, 2019
Keio University School of Medicine
Japan Agency for Medical Research and Development (AMED)
A research group led by Professor Akihiko Yoshimura and Project Assistant Professor Minako Ito of the Department of Microbiology and Immunology, Keio University School of Medicine, has discovered through experiments using a mouse model that newly discovered immune cells function in the chronic phase after a stroke, contributing to the recovery of neurological symptoms. Furthermore, they revealed that a drug already used as an antidepressant promotes the proliferation of these immune cells, thereby restoring neurological function and showing potential as a new therapeutic agent.
Stroke is a leading cause of death and of patients becoming bedridden. However, existing treatments for stroke are limited to the very early phase of onset, and the development of new, effective therapeutic agents for the chronic phase, long after onset, is highly anticipated. This research group has previously clarified the inflammatory process centered on macrophages in the acute phase, which occurs in the first few days after a stroke. However, it was believed that from one week after onset, the inflammation subsides and the immune system is no longer involved in the pathology.
Using a mouse model of stroke, this research group discovered that in the chronic phase after stroke onset, T cells, a type of lymphocyte responsible for adaptive immunity, accumulate in large numbers at the infarct site. Among these, regulatory T cells (Tregs) increase and control the neural repair process in the brain after a stroke. It was found that brain Tregs suppress activated astrocytes that damage nerve cells, thereby alleviating neurological symptoms. Furthermore, unlike Tregs in other tissues, these brain Tregs were found to possess serotonin receptors characteristic of the nervous system, and it was revealed that they are proliferated and activated by serotonin. When the stroke model mice were administered serotonin or a drug that increases serotonin in the brain (a type of antidepressant), brain Tregs increased and neurological symptoms improved. It is expected that antidepressants acting on brain serotonin will also be useful for treating stroke patients in the chronic phase (rehabilitation phase).
The results of this research were published in the online advance edition of the British scientific journal "Nature" on January 2, 2019 (GMT). They will also be published in the print edition of the journal on January 10.
For the full press release, please see below.