Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Natural glucose byproduct may prevent brain damage and cognitive impairment after diabetic coma

26.04.2005


A natural, non-toxic byproduct of glucose may prevent brain cell death and cognitive impairment in diabetics following an episode of severely low blood sugar, according to researchers at the San Francisco VA Medical Center (SFVAMC).



In research studies with rats, senior investigator Raymond A. Swanson, MD, and lead author Sang Won Suh, PhD, demonstrated the effectiveness of pyruvate, a naturally-occurring byproduct of glucose, when administered along with glucose after 30 minutes of diabetic coma. The therapy prevented brain damage and subsequent memory and learning impairment far better than treatment with glucose alone.

The study findings, appearing in the May 1, 2005 issue of Diabetes, have direct implications for the treatment of diabetic patients in hypoglycemic coma, according to the researchers.


Glucose is a form of sugar that serves as the body’s primary fuel. People with diabetes lack the ability to make insulin, the primary enzyme that metabolizes glucose and regulates its levels in the blood, and must inject insulin to make up for this lack. Abnormally low blood glucose is called hypoglycemia; severe hypoglycemia can cause coma.

"It’s estimated that between 2 and 15 percent of people with diabetes will have at least one episode of diabetic coma resulting from severe hypoglycemia," says Swanson, chief of the Neurology and Rehabilitation Service at SFVAMC and professor of neurology at UCSF.

"Anybody who’s worked at a busy emergency room has seen a patient like this," he adds. A patient admitted with severe hypoglycemia is immediately given glucose as a standard treatment. This restores consciousness right away, but may not always prevent the subsequent death of neurons and possible cognitive impairment, he says.

In an earlier paper, Swanson and Suh, an assistant adjunct professor of neurology at UCSF, demonstrated the cause of this brain cell death: hypoglycemia triggers the activation of an enzyme called PARP-1, which in turn prevents neurons from metabolizing glucose into pyruvate, which is used to power cells. Deprived of pyruvate, the neurons starve and die.

In the current study, Swanson and Suh discovered they could circumvent the action of PARP-1 and keep neurons alive by administering pyruvate directly.

The key to neuron survival is the amount of the dose: 100 times the normal blood level. Pyruvate usually circulates throughout the brain and body at low concentrations, but ordinarily cannot penetrate the blood-brain barrier. However, "when we increase the levels to 100-fold normal, it gets into the brain well enough to preserve the neurons," says Swanson. The paper concludes that "pyruvate may be an effective intervention for patients with severe hypoglycemia."

In the research study, male rats experienced hypoglycemia and subsequent coma after insulin administration. After 30 minutes of diabetic coma?determined by monitoring the animals’ brainwaves using EEG (electro-encephalogram) — one group of rats was restored to consciousness with the administration of glucose plus pyruvate. Another group received glucose only, which is the current standard treatment for hypoglycemic coma. A control "sham hypoglycemia" group was administered insulin and then immediately given glucose to prevent coma.

Six weeks later, the rats were tested for memory and learning using a standard test involving a maze. Rats that had received only glucose showed significant impairment of learning and memory compared to the control group. By contrast, rats that had received pyruvate along with glucose did not show any significant cognitive deficit compared to the control group.

Followup necropsy of brain tissue evaluated four areas of the hippocampus most vulnerable to damage from hypoglycemia: CA1, dentate granule cell, subiculum, and perirhinal cortex. The rats receiving glucose plus pyruvate had 70 to 90 percent less neuronal death than the rats given glucose only, indicating that pyruvate prevented neuronal death.

In a separate group of rats, the investigators also studied the protective effects of delayed administration of pyruvate. Hypoglycemic coma was induced using insulin and ended 30 minutes later with glucose only. The rats were then given pyruvate 1, 3, or 6 hours later. In the rats given pyruvate 1 hour after hypoglycemia was induced, all four regions of the brain were protected. A 3-hour delay achieved significant protection only in the dentate granule cell and the cortical areas. Pyruvate had no protective effect after 6 hours.

The current study findings have set the stage for two lines of future research, according to Swanson. One will involve the study of animals under circumstances less severe, and more realistic, than a 30-minute coma: "At this point, we need to also examine the effect of pyruvate after more moderate hypoglycemia, as more commonly experienced by diabetic patients." At the same time, Swanson believes that research on pyruvate therapy is ready to advance to the clinical level. "Pyruvate is a natural metabolite, present in our blood. There’s no reason to think that it would have any long-term adverse effects."

Additional authors of the study are Koji Aoyama, PhD, of SFVAMC and the UCSF Department of Neurology, and Yasuhiko Matsumori, PhD, and Jialing Liu, PhD, of SFVAMC and the UCSF Department of Neurosurgery.

Steve Tokar | EurekAlert!
Further information:
http://www.ncire.org

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>