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 Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>