Stroke: DHA reduces neuronal damage!

A lipid molecule derived from DHA, called NDP1, is able to keep brain and retina cells alive after stroke or other neurodegenerative and ocular disorders, as well as reduce the effect of oxygen free radicals. The role of NPD1 is to stimulate the production of a protein that promotes cell survival. Understanding this mechanism could aid the development of possible therapies for ischemic stroke and retinal degenerations.

This is reported by a study conducted by researchers from the LSU Health School of Medicine in New Orleans (USA) and published in the journal Cell Death and Differentiation.

Stroke is one of the leading causes of death and disability in Italy

Stroke is a cerebrovascular injury caused by interruption of blood flow to the brain due to obstruction or rupture of an artery. When blood flow is interrupted, neurons deprived of oxygen and necessary nutrients—even for just a few minutes—begin to die. Cerebral stroke is one of the most frequent causes of death after age 65, but young people can also be affected. In Italy, it is the third leading cause of death, after cardiovascular diseases and cancer, and the primary cause of disability. Stroke is also the second most common form of dementia. Symptoms vary depending on the brain area damaged. Two types of stroke are distinguished: ischemic stroke, the most common, caused by vessel occlusion, and hemorrhagic stroke caused by vessel rupture. Risk factors for stroke include:

• age
• family history
• sex
• hypertension
• diabetes mellitus
• hypercholesterolemia
• smoking
• heart diseases
• excess alcohol consumption

Many of these risk factors can be eliminated by following a healthy lifestyle: a proper diet and regular physical activity also help maintain an adequate body weight. Obesity is also an important risk factor for stroke. Numerous studies have shown that a diet rich in omega 3, in adults and the elderly, supports memory and cognitive function maintenance and is associated with a lower risk of stroke. In particular, EPA appears to prevent ischemic stroke, as some studies attribute the preventive effect to the antithrombotic action induced by this omega-3. DHA is also essential for proper brain function and necessary for nervous system and vision development. It is the main lipid composing neuron and retina membranes and is essential for their development and function (link).

A lipid derived from DHA activates the neuronal survival mechanism

The main results of the research demonstrated that DHA gives rise to a signaling molecule called NPD1, which in turn enhances the production and availability of a protein that facilitates neuron preservation. This protein, called Iduna, is known as a "survival" protein for its ability to protect the brain from stroke effects. Iduna is produced when, following brain injury, the body triggers mechanisms needed to protect against further damage. The important role of DHA in the proper functioning and development of the nervous system has long been known, as well as its role in vision mechanisms and retina function. Previous studies have shown that NPD1 can protect retinal cells in visual degeneration. As explained by Nicolas Bazan, professor and director of the Neuroscience Center at LSU Health School of Medicine, these results are significant as they show the action of NPD1, a lipid mediator that "on demand" modulates the amount of Iduna protein, which is crucial in limiting brain damage.

A study conducted on human cells

During the study, researchers chose two different types of human retinal cells for a series of experiments. In particular, they added NPD1 to the cells one hour after an experimental stroke and observed increased production and availability of the Iduna protein. Iduna facilitates repair of damaged DNA and protects against a form of programmed cell death by suppressing production of a destructive protein. Results also showed that NDP1 reached peak activity six hours after oxidative stress occurring post neuronal cell death. These results thus suggest a circuit where NPD1 promotes Iduna activity when oxidative stress activates NPD1 formation, which in turn activates Iduna. The protective function of Iduna protein in cells is important not only in stroke but also for eye health and plays a key role in maintaining photoreceptors, the light-sensitive cells in the retina. In degenerative retinal diseases, photoreceptors are damaged, and resulting oxidative stress prevents DHA uptake, reduces NPD1 synthesis, and causes degeneration of the photoreceptors themselves.

The DHA-NPD1-Iduna mechanism as the basis for future therapies?

According to the researchers, the NPD1 mediator derived from DHA increases Iduna expression, a key regulator of cell survival, blocking cell death. As Professor Bazan stated, "Further clarification of the molecular details of the DHA-NPD1-Iduna relationship could contribute to possible therapeutic interventions for retinal degenerations and ischemic stroke."

Source: Ludmila Belayev, Pranab K Mukherjee, Veronica Balaszczuk, Jorgelina M Calandria, Andre Obenaus, Larissa Khoutorova, Sung-Ha Hong and Nicolas G Bazan. “Neuroprotectin D1 upregulates Iduna expression and provides protection in cellular uncompensated oxidative stress and in experimental ischemic stroke.” Cell death and differentiation