The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 16 No. 7 • August 2013


Chronic Inflammation Impairs Adult Hippocampal Neurogenesis

Protection Against Radiation Damage By Hydrogen

Using a cranial radiation injury model in adult rats, researchers found that using a dose of 10 Gray cranial irradiation with x-rays, the radiation spared roughly 30% of the neuron progenitor cells proliferative capacity but completely eliminated the production of neurons (neurogenesis).1 As the scientists reported, “irradiation caused a striking inflammatory response characterized by the persistence of activated microglia relative to the minimal levels in normal control animals.” “If inflammation were the primary cause of the lack of neurogenic signaling within the dentate subgranule zone (SGZ), then inflammatory blockade would be expected to restore neurogenesis. Treating the irradiated animals with indomethacin (a non-steroidal antiinflammatory drug) during and after radiation exposure “partially restored the relative proportion of proliferative cells adopting a neuronal fate relative to untreated, irradiated animals (37% versus 15%, respectively).”1

The researchers also studied the effect of LPS (a bacterial cell wall component that induces a strong immune response) injected into adult female rats to produce an inflammatory cascade. They measured a 240% increase in the density of activated microglia in the dentate gyrus that was accompanied by a 35% decrease in hippocampal neurogenesis. This effect was completely blocked by systemic treatment with indomethacin. (Indomethacin under normal conditions had no effect on neurogenesis.)

The scientists found that activated microglia produced potent inflammatory cytokines including IL-1beta, TNF-alpha (tumor necrosis factor alpha), interferon gamma, and IL-6.1 Progenitor cells were allowed to differentiate in the presence of each of these cytokines with the result that IL-6 or TNF-alpha decreased in vitro neurogenesis by about 50%, whereas under these test conditions IL-1beta and interferon gamma had no significant effect.

This may be a mechanism by which NSAIDs such as indomethacin protect against Alzheimer’s disease, which does involve inflammation. It has been known for many years that there is a negative correlation between the use of NSAIDs and the incidence of Alzheimer’s.

Another paper2 also reports increased inflammation and impaired neurogenesis as a result of exposure to radiation.

Radiation Protection By Hydrogen

Hydrogen is an effective radioprotective antioxidant,2A as it potently scavenges hydroxyl radicals, which are the source of most tissue damage caused by radiation. Of particular importance, too, is the fact that hydrogen reaches mitochondria, thus providing protection against hydroxyl radicals there as well as other areas of irradiated tissue. As reported in a paper on targeted delivery of radioprotective agents to mitochondria,3 mitochondria are the principle sources of the reactive oxygen and nitrogen species, especially hydroxyl radicals and peroxynitrite, that are importantly involved in irradiation-induced apoptosis (programmed cell death); hydrogen is a potent scavenger of both hydroxyl radicals and peroxy­nitrite.

Another natural product providing protection against the oxidative stress resulting from radiation is epicatechin4 (found in cocoa, grapes, tea, and apples).

References

1. Monje et al. Inflammatory blockade restores adult hippocampal neurogenesis. Science. 302:1760-5 (2003).
2. Rola et al. High-LET radiation induces inflammation and persistent changes in markers of hippocampal neurogenesis. Radiat Res. 164:556-560 (2005).
2A. Qian et al. Radioprotective effects of hydrogen in cultured cells and mice. Free Rad Res. 44(3):275-82 (2010).
3. Zabbarova and Kanai. Targeted delivery of radioproective agents to mitochondria. Mol Interv. 8(6):294-302 (2008).
4. Sinha et al. Epicatechin ameliorates ionising radiation-induced oxidative stress in mouse liver. Free Rad Res. 46(7):842-9 (2012).

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