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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Ethyl pyruvate protects against lipopolysaccharide-induced white matter injury in the developing rat brain
Yingyan Wang1, Ping Yin, Shanying Huang
1Pediatric Department of Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Insights
Ethyl pyruvate (EP) protects neonatal rat brains from white matter injury caused by inflammation. EP reduces cell death and inflammation, preserving white matter integrity after lipopolysaccharide exposure.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Neonatal white matter injury (NWMI) is a significant cause of long-term disability.
- Ethyl pyruvate (EP) demonstrates neuroprotective effects in various brain injury models.
- The efficacy of EP in NWMI remains largely unexplored.
Purpose of the Study:
- To investigate the protective effects of ethyl pyruvate (EP) against lipopolysaccharide (LPS)-induced white matter damage in neonatal rats.
- To elucidate the underlying mechanisms of EP's action, focusing on inflammation and apoptosis.
Main Methods:
- Neonatal Sprague-Dawley rat pups (postnatal day 5) received intracerebral LPS injection to induce white matter injury.
- Ethyl pyruvate (EP) was administered intraperitoneally at 40mg/kg at immediate, 1h, and 12h post-LPS exposure.
- Assessment of white matter damage included ventricle dilation, oligodendrocyte counts (O4+, O1+), apoptosis, myelination, microglial and astrocyte activation, and inflammatory markers (TNF-α, IL-1β).
Main Results:
- EP treatment significantly reduced LPS-induced ventricle dilation and loss of oligodendrocytes.
- EP administration mitigated oligodendrocyte apoptosis and hypomyelination.
- EP suppressed inflammatory responses by inhibiting microglial and astrocyte activation and decreasing TNF-α and IL-1β expression.
- EP prevented the elevation of cleaved caspase-3, an apoptosis marker, in the periventricular white matter.
Conclusions:
- Ethyl pyruvate (EP) confers potent protection against LPS-induced neonatal white matter injury.
- EP's protective effects are mediated through its anti-inflammatory and anti-apoptotic properties.
- EP represents a potential therapeutic agent for neonatal white matter injury.
Abstract:
The neuroprotective effects of ethyl pyruvate (EP) have been proved in several brain injury models, yet very little is known about its action on neonatal white matter injury. To investigate the effect of EP on white matte damage, a stereotactic intracerebral injection of lipopolysaccharide (LPS, 1mg/kg) was performed on postnatal day 5 Sprague-Dawley rat pups, and EP was administrated intraperitoneally at a dose of 40mg/kg immediately, 1h and 12h after LPS exposure. Significantly, treatment with EP reduced LPS-induced ventricle dilation, loss of O4+ and O1+ oligodendrocytes, apoptosis of oligodendrocytes, and hypomyelination. The protective effect of EP was associated with suppressed inflammatory responses, indicated by the inhibition of activation of microglia and astrocytes, as well as the decreased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in rat brains. Also, EP prevented the elevation of cleaved caspase-3 in periventricular white matter tissue after LPS insult. Taken together, these results suggest that EP confers potent protection against LPS-induced white matter injury via its anti-inflammatory and anti-apoptotic properties.
