[Show abstract][Hide abstract] ABSTRACT: Accumulated evidences have established that inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Sulindac is well known as a nonsteroidal anti-inflammatory drug. However, little is known regarding the effect of sulindac in acute cerebral ischemia. Here, we designed this study to investigate the potential protective effects of sulindac in focal cerebral ischemia and the mechanisms underlying in vivo.
Focal cerebral ischemia was induced in male Sprague-Dawley rats by permanent middle cerebral artery occlusion (pMCAO). Sulindac was administrated at dose of 4, 10, or 20mg/kg at 30min before the operation. Neurological deficit scores, brain water content and infarct volumes were measured at 24h after pMCAO. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction were used for examining the mediators involved in Wnt/β-catenin signaling pathway, including the positive regulators dishevelled (Dvl) and β-catenin, the negative regulators adenomatous polyposis coli (APC), and P-β-catenin, as well as the downstream targets Bcl-2, Bax and claudin-5.
Compared with Vehicle group, 20mg/kg sulindac reduced neurological deficits, brain water content and infarct volumes. The same dose of sulindac upregulated the expression of Dvl, β-catenin, Bcl2 and claudin-5, and downregulated APC, P-β-catenin and Bax compared with Vehicle group.
These results showed that sulindac had a significant beneficial effect in cerebral ischemia; this effect may be correlated with the activation of the Wnt/β-catenin signaling.
[Show abstract][Hide abstract] ABSTRACT: Background:
It has been proved that pre-treatment with leonurine could protect brain tissue against ischemic injury by exerting antioxidant effects and regulating mitochondrial function. Whether this protective effect applies to acute phase after cerebral ischemia, we therefore investigate the potential neuroprotective role of leonurine and the underlying mechanisms in cerebral ischemia.
Focal cerebral ischemia was induced in adult male Sprague-Dawley rats by permanent middle cerebral artery occlusion (MCAO). Leonurine was administered intraperitoneally at 7.5 or 15 mg/kg/d at 2h after surgery, then once daily thereafter. Neurological deficit, brain water content, and infarct volume were measured at 24h, 72 h, and 7d after stroke. Superoxide dismutase (SOD), catalase (CAT) activities, and malondialdehyde (MDA) content were also measured by spectrophotometer to evaluate oxidative reactions, and the expression of uncoupling protein 4 (UCP4), Bcl-2, and Bax were detected by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical staining (IHC), and western blot, while the ultrastructure of the mitochondria were observed under transmission electron microscope.
Leonurine significantly alleviated neurological deficit, decreased brain water content and infarct volume after ischemic stroke, which was accompanied by decreased levels of MDA and Bax, increased activities of SOD, CAT, UCP4, and Bcl-2, and restored ultrastructure of mitochondria.
The results showed that leonurine protected brain injury by increased activities of UCP4, SOD, CAT and Bcl-2, decreased levels of MDA and Bax, and ameliorated ultrastructure of mitochondria in experimental stroke.
[Show abstract][Hide abstract] ABSTRACT: Inflammatory damage plays a pivotal role in cerebral ischemia and may represent a target for treatment. Pigment epithelium-derived factor (PEDF) is proven to possess neuroprotective property. But there is little known about the intrinsic PEDF after cerebral ischemia. This study evaluated the time course expression of the intrinsic PEDF and its underlying regulation mechanisms after cerebral ischemia. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion. Telmisartan (PPARγ agonist) and GW9662 (PPARγ antagonist) were systemically administered to explore the effect on PPARγ, PEDF, NF-κB and MMP-9 expression at 24 h after cerebral ischemia by western blot and qRT-PCR. The neurological deficits, brain water content and infarct volume were measured. Compared with normal group, the expressions of PEDF and PPARγ decreased, and the expression of NF-κB and MMP-9 increased at early stage after ischemia (P < 0.05). Compared with the vehicle group, the decrease of PEDF and PPARγ was significantly up-regulated and the increase of NF-κB and MMP-9 was down-regulated by telmisartan at 24 h (P < 0.05). The neurological deficits, brain water content and infarct volume were dramatically alleviated by telmisartan (P < 0.05). Telmisartan's effects were reversed by GW9662 co-administration (P < 0.05). The expression of intrinsic PEDF was down-regulated at the early stage of cerebral ischemia. The protective effects of intrinsic PEDF by activating PPARγ pathway may be one of the strategic targets for cerebral ischemic therapies.
No preview · Article · Jun 2012 · Neurochemical Research
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Berberine (BBR) has gained attention for its vast beneficial biological effects through immunomodulation, anti-inflammatory and anti-apoptosis properties. Inflammatory and apoptosis damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The aim of this study was to explore BBR's effect in ischemic injury and the role of the Akt/GSK (glycogen synthase kinase) signaling cascade in mediating the anti-apoptosis and anti-inflammatory effects in the rat brain of permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley rats were subjected to pMCAO and randomly assigned into four groups: Sham (sham-operated) group, pMCAO (pMCAO+0.9% saline) group, BBR-L (pMCAO+BBR 10 mg/kg) and BBR-H (pMCAO+BBR 40 mg/kg) group. BBR was administered immediately after pMCAO and the neuroprotection was detected. Phospho-Akt (pAkt), phospho-glycogen synthase kinase 3-β (pGSK3β), phospho-cAMP response element binding protein (pCREB), nuclear factor-kappa B (NF-κB) and claudin-5 in ischemic cerebral cortex were detected by immunohistochemistry, reverse transcription-polymerase chain reaction and western blotting. Compared with pMCAO group, BBR dramatically lessened neurological deficits scores, brain water contents and infarct sizes, upregulated the expression of pAkt, pGSK3β, pCREB and claudin-5, and decreased the nuclear accumulation of NF-κB (P<0.05) in ischemic brain. The results showed that BBR reduced ischemic brain injury after pMACO, and this effect may be via the increasing the activation of Akt/GSK signaling and claudin-5, and decreasing NF-κB expression.
[Show abstract][Hide abstract] ABSTRACT: Inflammatory damage is known to be involved in ischemic stroke. Luteolin has been proved to elicit a series of biologic effects through its anti-inflammatory property in multiple sclerosis and rheumatoid arthritis. Whether this protective effect applies to ischemic injury in brain is still unknown, we therefore investigate the potential neuroprotective role of luteolin in ischemic stroke and the underlying mechanisms.
Male Sprague-Dawley rats were subjected to pMCAO and luteolin was administered intraperitoneally immediately after surgery, then once daily thereafter. Neurological deficit, infarct volume, and brain water content were measured at 24 h and 72 h after stroke. The expression of TLR4, TLR5, and NF-κB were measured by real-time PCR, immunohistochemical staining (IHC), and Western blot. P38MAPK and extracellular signal-regulated kinase (ERK) were detected by IHC, and Western blot.
Compared with pMCAO group, luteolin significantly alleviated neurological deficit, decreased infarct volume and suppressed edema after ischemic stroke, which were accompanied with decreased expression of TLR4, TLR5, NF-κB and p-p38MAPK. Meanwhile, luteolin activated the expression of p-ERK1/2 (P<0.05).
Luteolin protected the brain from the damage caused by pMCAO, and this effect may be through downregulation of TLR4, TLR5, NF-κB, p38MAPK and upregulation of ERK expression.