Chemical reaction keeps Stroke-damaged brain from repairing itself

Stuart A. Lipton, M.D., Ph.D., is director of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at Sanford-Burnham Medical Research Institute and a clinical neurologist. 

Credit: Sanford-Burnham Medical Research Institute.

Nitric oxide, a gaseous molecule produced in the brain, can damage neurons.

When the brain produces too much nitric oxide, it contributes to the severity and progression of stroke and neurodegenerative diseases such as Alzheimer's.

Researchers at Sanford-Burnham Medical Research Institute recently discovered that nitric oxide not only damages neurons, it also shuts down the brain's repair mechanisms.

Their study was published by the Proceedings of the National Academy of Sciences (PNAS) the week of February 4.

"In this study, we've uncovered new clues as to how natural chemical reactions in the brain can contribute to brain damage—loss of memory and cognitive function—in a number of diseases," said Stuart A. Lipton, M.D., Ph.D., director of Sanford-Burnham's Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and a clinical neurologist.

Lipton led the study, along with Sanford-Burnham's Tomohiro Nakamura, Ph.D., who added that these new molecular clues are important because "we might be able to develop a new strategy for treating stroke and other disorders if we can find a way to reverse nitric oxide's effect on a particular enzyme in nerve cells."

Nitric oxide inhibits the neuroprotective ERK1/2 signaling pathway Learning and memory are in part controlled by NMDA-type glutamate receptors in the brain.

These receptors are linked to pores in the nerve cell membrane that regulate the flow of calcium and sodium in and out of the nerve cells. When these NMDA receptors get over-activated, they trigger the production of nitric oxide.

In turn, nitric oxide attaches to other proteins via a reaction called S-nitrosylation, which was first discovered by Lipton and colleagues. When those S-nitrosylated proteins are involved in cell survival and lifespan, nitric oxide can cause brain cells to die prematurely—a hallmark of neurodegenerative disease.

In their latest study, Lipton, Nakamura and colleagues used cultured neurons as well as a living mouse model of stroke to explore nitric oxide's relationship with proteins that help repair neuronal damage.

They found that nitric oxide reacts with the enzyme SHP-2 to inhibit a protective cascade of molecular events known as the ERK1/2 signaling pathway. Thus, nitric oxide not only damages neurons, it also blocks the brain's ability to self-repair.

Scottish Mullite: Silicate Material That Can Cut Diesel Pollution

Platinum, a rare and expensive metal, is currently used in diesel engines to try to control the amount of pollution released into the air.

Scientists have now developed a new material that is much more effective than platinum in reducing pollution. University of Texas at Dallas scientists have found that oxide mullite could reduce pollution up to 45 percent compared to platinum crystals.

Mullite or porcelainite is a rare silicate mineral of post-clay genesis, They claim that mullite is less expensive to produce compared to platinum crystals.

Mullite was first described in 1924 for an occurrence on the Isle of Mull, Scotland. It occurs as argillaceous inclusions in volcanic rocks in the Isle of Mull and also with emerylike rocks in Sithean Sluaigh, Scotland.

"Many pollution control and renewable-energy applications require precious metals that are limited - there isn't enough platinum to supply the millions and millions of automobiles driven in the world," said Dr Kyeongjae "K J" Cho, professor at the University of Texas.

"Mullite is not only easier to produce than platinum, but also better at reducing pollution in diesel engines."

Diesel engines give higher fuel efficiency compared to gasoline but produce more nitric oxide (NO) and nitrogen dioxide (NO2), which are quite harmful to human health.

Recently, the World Health Organisation (WHO) upgraded the classification of diesel engine exhaust as carcinogenic in humans, putting it in the same category as cigarette smoke and asbestos.

Countries throughout the world have drafted guidelines to reduce diesel air pollution in the next decade.

The new material developed by scientists could be a new cheap and effective way to reduce pollution.

The discovery was made while analysing the chemical components of mullite.

The team used advanced computer modelling techniques to analyse how different forms of the mineral interacted with Oxygen (O) and Nitrous Oxide (NOx).

The study revealed that the oxide mullite reduces pollution up to 45 percent compared to platinum crystals.

"Our goal to move completely away from precious metals and replace them with oxides that can be seen commonly in the environment has been achieved," Dr Cho said.

"We've found new possibilities to create renewable, clean energy technology by designing new functional materials without being limited by the supply of precious metals."