Mechanism that stimulates brain self-healing after stroke discovered
Researchers have identified a molecular pathway that stimulates damaged cells to self-repair after ischemic stroke.Researchers from Tokyo Medical and Dental University have discovered a mechanism that allows people who have suffered an ischemic stroke to restore brain function. The self-repairing properties of cells could be used to develop therapies.
Scientists examined changes in the production of lipid metabolites produced by brain tissue damage in mice after ischemic stroke. The analysis showed that levels of the fatty acid dihomo-gamma-linolenic acid (DGLK) and its derivatives increased after the stroke.
DGLC is part of a family of omega-6 fatty acids with anti-inflammatory properties. Researchers found that the release of DGLA is regulated by the enzyme PLA2GE2. By controlling the expression of this enzyme in mice, the researchers found that it influenced the repair of brain cells. Deficiency of the enzyme led to more inflammation, reduced expression of factors that stimulate neuronal repair, and greater tissue loss.
The researchers showed that PLA2GE2 increases the production of the protein peptidylarginine deaminase 4 (PADI4). It regulates the transcription of genes involved in brain repair and inflammation. Expression of this protein in mice limited the extent of tissue damage and inflammation after stroke.
The researchers mapped the entire signaling pathway involved in brain repair. Although the analysis is based on mouse models, the scientists found that neurons surrounding the damaged stroke site express PLA2GE2 and PADI4 in humans as well. This means that a similar repair pathway may work in humans as well.
The discovery of a new mechanism that triggers brain repair could lead to the development of therapeutics that enhance the effects of PADI4 and speed recovery from ischemic stroke. Researchers are planning clinical trials of this method.