Cerebral ischemia is a neurological disorder with high mortality. Quercetin is a
flavonoid compound that is abundant in vegetables and fruits. It exerts anti-inflammatory
and anti-apoptotic effects. This study investigated the neuroprotective effects of
quercetin in focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle
cerebral artery occlusion (MCAO) to induce focal cerebral ischemia. Quercetin or vehicle
was injected 30 min before the onset of ischemia. A neurological function test, brain
edema measurement, and 2,3,5-triphenyltetrazolium chloride staining were performed to
elucidate the neuroprotective effects of quercetin. Western blot analysis was performed to
observe caspase-3 and poly ADP-ribose polymerase (PARP) protein expression. MCAO leads to
severe neuronal deficits and increases brain edema and infarct volume. However, quercetin
administration attenuated the MCAO-induced neuronal deficits and neuronal degeneration. We
observed increases in caspase-3 and PARP protein levels in MCAO-operated animals injected
with vehicle, whereas quercetin administration attenuated these increases in MCAO injury.
This study reveals the neuroprotective effect of quercetin in an MCAO-induced animal model
and demonstrates the regulation of caspase-3 and PARP expression by quercetin treatment.
These results suggest that quercetin exerts a neuroprotective effect through preventing
the MCAO-induced activation of apoptotic pathways affecting caspase-3 and PARP
expression.
Cerebral ischemia is a major cause of death and neurological disability. It also leads to severe brain tissue damage by excessive generation of oxidative stress. Quercetin is a bioflavonoid substance that acts an antioxidant agent and exerts a neuroprotective effect against cerebral ischemia. The aim of this study was to detect specific proteins that are differentially expressed in response to quercetin treatment in focal cerebral ischemia. Adult male rats were intraperitoneally injected with vehicle or quercetin (10 mg/kg) 30 min prior to right middle cerebral artery occlusion (MCAO). Brain tissues were collected 24 h after MCAO surgery and right cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry. MCAO leads to neurological behavior disorders, infarction, and histopathological change. However, quercetin treatment alleviated MCAO-induced neuronal deficits and damages. We identified specific proteins differentially expressed between vehicle- and quercetin-treated animals. Among these detected proteins, isocitrate dehydrogenase [NAD], adenosylhomocysteinase, pyruvate kinase, and ubiquitin carboxy terminal hydrolase L1 were decreased in vehicle-treated animals, while quercetin administration alleviated the MCAO-induced decreases in these proteins. However, 60 kDa heat shock protein and collapsin response mediator protein 2 were increased in the vehicle-treated animals, and quercetin treatment attenuated increases in these proteins. The expression changes in these proteins were confirmed by Western blot and reverse transcription-PCR analyses. These proteins are associated with cellular differentiation, metabolism, and oxidative stress related proteins. These results suggest that quercetin reduces ischemic injury by modulating the expression of various proteins in focal cerebral ischemia.
Quercetin is a plant flavonoid that has anti-oxidant, anti-inflammatory, anti-cancer, and anti-ischemic properties. Moreover, quercetin exerts neuroprotective effects against focal cerebral
ischemia. Protein phosphatase 2A (PP2A) is a form of serine/threonine phosphatase that modulates various biological functions. Among PP2A subunit types, subunit B exists abundantly in brain
tissue and plays an essential function in nervous system. We previously reported the decrease of PP2A subunit B in focal cerebral animal model. This study explored the change of PP2A subunit
B expression by quercetin treatment in cerebral ischemic animal model and glutamate-treated hippocampal-derived (HT22) cell culture. Quercetin (10 mg/kg) or vehicle was injected
intraperitoneally into male rats before 30 min of middle cerebral artery occlusion (MCAO), and cerebral cortices were isolated 24 hr after MCAO. MCAO induced the neurological behavioral
deficit and increased infarct volume. However, quercetin treatment attenuated the increase of neurological deficit and infarction. We detected the alleviation of MCAO-induced the decrease in
PP2A subunit B by quercetin treatment using a proteomic approach. Reverse-transcription PCR and Western blot analyses confirmed lower PP2A subunit B expression levels in MCAO group with
vehicle. However, quercetin treatment attenuated MCAO-induced this reduction. We also observed the neuroprotective effect of quercetin and the change of PP2A subunit B expression in
glutamate-exposed HT22 cells. Glutamate exposure dramatically reduced cell viability and PP2A subunit B expression, and quercetin treatment significantly improved these decreases. We clearly
showed that quercetin performs a neuroprotective function and modulates down-regulation of PP2A subunit B against MCAO injury and glutamate toxicity. Thus, our finding suggests that the
regulation of PP2A subunit B by quercetin contributes to neuroprotective function in ischemic brain injury.
Lipopolysaccharide (LPS) acts as an endotoxin, releases inflammatory cytokines, and promotes an inflammatory response in various tissues. This study investigated whether LPS modulates neuroglia activation and nuclear factor kappa B (NF-κB)-mediated inflammatory factors in the cerebral cortex. Adult male mice were divided into control animals and LPS-treated animals. The mice received LPS (250 μg/kg) or vehicle via an intraperitoneal injection for 5 days. We confirmed a reduction of body weight in LPS-treated animals and observed severe histopathological changes in the cerebral cortex. Moreover, we elucidated increases of reactive oxygen species and oxidative stress levels in LPS-treated animals. LPS administration led to increases of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Iba-1 and GFAP are well accepted as markers of activated microglia and astrocytes, respectively. Moreover, LPS exposure induced increases of NF-κB and pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Increases of these inflammatory mediators by LPS exposure indicate that LPS leads to inflammatory responses and tissue damage. These results demonstrated that LPS activates neuroglial cells and increases NF-κB-mediated inflammatory factors in the cerebral cortex. Thus, these findings suggest that LPS induces neurotoxicity by increasing oxidative stress and activating neuroglia and inflammatory factors in the cerebral cortex.
Cerebral ischemia is a neurological disorder that causes permanent disability and is sometimes fatal. Epigallocatechin gallate (EGCG) is a natural polyphenol that exerts beneficial antioxidant and anti-inflammatory effects. The aim of this study was to investigate the neuroprotective effects of EGCG against cerebral ischemia. Middle cerebral artery occlusion was surgically initiated to induce focal cerebral ischemia in adult male rats. EGCG (50 mg/kg) or vehicle was intraperitoneally injected just prior to middle cerebral artery occlusion (MCAO) induction. Neuronal behavior tests were performed 24 hr after MCAO. Brain tissues were isolated to evaluate infarct volume, histological changes, apoptotic cell death, and caspase-3 and poly ADP-ribose polymerase (PARP) levels. MCAO injury led to serious functional neurological deficits and increased infarct volume. Moreover, it induced histopathological lesions and increased the numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the cerebral cortex. However, EGCG improved MCAO-induced neurological deficits and reduced infarct volume, alleviated histopathological changes, and decreased TUNEL-positive cells in the cerebral cortex of MCAO rats. Western blot analysis showed increases of caspase-3 and PARP expression levels in MCAO rats with vehicle, whereas EGCG administration alleviated these increases after MCAO injury. These results demonstrate that EGCG exerts a neuroprotective effect by regulating caspase-3 and PARP proteins during cerebral ischemia. In conclusion, we suggest that EGCG acts as a potent neuroprotective agent by modulating the apoptotic signaling pathway.
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