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 MS or other such disorders.
In an article in the January 5, 2006, issue of 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 MS, they found elevated levels of AEA, 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 AEA levels.
Importantly, they found that adding AEA 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 AEA 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 AEA effects the cells, inflammatory damage was increased.
The researchers also explored the mechanism by which AEA prevents inflammatory damage. They found th at, when AEA 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 AEA in injured brain tissue might act as a "gatekeeper" and an important "negative-feedback loop within the CNS [central nervous system] 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. Therefore, elucidating the pathology of the endocannabinoid system during neuroinflammation and neurodegeneration might open new avenues of therapeutic interventions in the future."