Sugar Compound Protects Brain from Stroke by Producing Hydrogen Gas

Authors
Journal
Free Radical Biology and Medicine
Year
DOI
10.1016/j.freeradbiomed.2013.08.004
Study Type
Rat
Outcome
Positive
Peer Reviewed
Yes
Country
China
Health Condition
Stroke
Body System
Nervous System

TL;DR

Lactulose, a type of sugar, can protect rat brains from damage caused by a stroke by producing healing hydrogen in the gut.

Key Finding

Oral lactulose reduced brain damage and improved neurological recovery in rats with stroke-like injuries by triggering hydrogen production in the gut and activating protective cellular pathways.

Summary

Researchers gave rats with stroke-like brain injuries a sugar compound called lactulose by mouth. The lactulose was broken down by bacteria in the gut to produce hydrogen gas, which the rats absorbed. Compared to untreated rats, those receiving lactulose showed better recovery, smaller brain damage areas, and less cell death. The protective effect appeared to work by activating a cellular defense system called Nrf2 that reduces harmful molecules produced during stroke.

Practical Takeaway

This rat study suggests lactulose might help protect the brain during stroke by generating hydrogen internally, and the effect was stronger than a standard stroke medication tested. However, this is early animal research only—human studies would be needed to determine if lactulose offers any benefit for stroke prevention or recovery in people. The study does not establish safe doses or whether this approach would work in humans.

Abstract

Molecular hydrogen has been proved effective in ameliorating cerebral ischemia/reperfusion (I/R) injury by selectively neutralizing reactive oxygen species. Lactulose can produce considerable amount of hydrogen through fermentation by the bacteria in the gastrointestinal tract. To determine the neuroprotective effects of lactulose against cerebral I/R injury in rats and explore the probable mechanisms, we carried out this study. The stroke model was produced on Sprague-Dawley(SD) rats through middle cerebral artery occlusion(MCAO). Intragastric administration of lactulose substantially increased hydrogen breath concentration. Behavioral and histopathological verifications matched biochemical findings. Behaviorally, rats in lactulose administration group won higher neurological scores and showed shorter escape latency time in Morris test. Morphologically, 2,3,5-triphenyltetrazolium chloride (TTC) showed smaller infarction volume; Nissl staining manifested relatively clear and intact neurons and TUNEL staining showed less apoptotic neurons. Biochemically, lactulose decreased brain malondialdehyde(MDA) content, caspase-3 activity, 3-nitrotyrosine(3-NT) and 8-hydroxy-2-deoxyguanosine(8-OHdG) concentration and increased superoxide dismutase(SOD) activity. And the effects of lactulose were superior to edaravone. Lactulose orally administered activated the expression of NF-E2-related factor 2(Nrf2) in the brain verified by RT-PCR and Western blot. The antibiotics suppressed the neuroprotective effects of lactulose via reducing hydrogen production. Our study for the first time demonstrated a novel therapeutic effect of lactulose on cerebral ischemia/reperfusion injury and the probable underlying mechanisms. Lactulose intragastrically administered possessed neuroprotective effects on cerebral I/R injury in rats, which could be attributed to hydrogen production by the fermentation of lactulose through intestinal bacteria and Nrf2 activation.