Anandamide, an endocannabinoid, protects neurons from inflammation after brain damage

Some clinical studies have indicated that marijuana or its active cannabinoid ingredient alleviates symptoms of the inflammatory disease, multiple sclerosis.

Also, researchers have found that the brain's natural " endocannabinoids " are released after brain injury and are believed to alleviate neuronal damage.
However, scientists have not understood how such substances act within the brain's own immune system.

Now, experiments by Oliver Ullrich and colleagues have pinpointed how one of the brain's endocannabinoids protects neurons from inflammation after such damage.
They say their studies could lead to new drugs to treat the inflammation and brain degeneration from multiple sclerosis or other such disorders.

In an article published in the journal Neuron, the researchers reported experiments showing how the endocannabinoid anandamide ( AEA ) protects brain cells from inflammation. Such a role in the brain's immune system is distinct from cannabinoids' effects on neuronal signaling that produce the behavioral effects of marijuana.

When Ullrich and colleagues analyzed brain tissue from people with multiple sclerosi, they found elevated levels of anandamide, compared to healthy tissue. And in studies with mouse brain slices, they found that inducing damage with a brain-cell-exciting chemical, called NMDA, caused an invasion of the brain's immune cells, called microglia, and an increase in anandamide levels.
Importantly, they found that adding anandamide to such damaged brain tissue abolished inflammatory damage to the brain cells, but did not reduce the primary "excitotoxic" damage from the chemical. They found similar effects of anandamide when they damaged the brain tissue by depriving it of oxygen and glucose.

The researchers also found that when they used a drug to block the receptors on microglial cells by which anandamide effects the cells, inflammatory damage was increased.

The researchers also explored the mechanism by which anandamide prevents inflammatory damage. They found that, when anandamide plugs into its receptors on activated microglial cells, it basically activates a specific molecular signaling pathway that suppresses the production of inflammation-causing nitric oxide, which would otherwise cause brain injury.

The researchers concluded that the release of anandamide in injured brain tissue might act as a "gatekeeper" and an important "negative-feedback loop” within the CNS immune system needed to reduce the extent of the inflammatory response and to limit neurodegenerative immune reactions after primary brain damage.

" Moreover, endocannabinoid signaling strongly suppresses attack of microglial cells on nondamaged neurons," they wrote, "suggesting also a physiological function of the endocannabinoid system in maintaining a protective and healthy CNS microenvironment."

They also concluded that " the endocannabinoid system represents a local messenger system between the nervous and immune system and is obviously involved in the control of immune activation and neuroprotection.”

Source: Neuron, 2006