Luteolin downregulates TLR4, TLR5, NF-κB and p-p38MAPK expression, upregulates the p-ERK expression, and protects rat brains against focal ischemia.

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.

Qiao H ，Zhang X ，Zhu C ，Dong L ，Wang L ，Zhang X ，Xing Y ，Wang C ，Ji Y ，Cao X ... -  《-》

Tanshinone II A down-regulates HMGB1, RAGE, TLR4, NF-kappaB expression, ameliorates BBB permeability and endothelial cell function, and protects rat brains against focal ischemia.

Inflammatory damage plays an important role in cerebral ischemic pathogenesis. HMGB1-induced NF-kappaB activation pathway has been gaining recognition as a key contributor to the proinflammatory response. Tanshinone II A (Tan II A) has been proved to elicit a series of biologic effects through its antiinflammatory property. But the mechanism underlying is poorly understood. This study evaluated the Tan II A's protective role in cerebral ischemia and its potential mechanism. Male Sprague-Dawley rats were subjected to pMCAO. Experiment 1 was used to evaluate the longitudinal expression of HMGB1, RAGE and TLR4 and NF-kappaB in the cerebral ischemia. Experiment 2 was used to detect Tan II A's neuroprotection. At 24 h after pMCAO, neurologic deficit, brain water content and infarct size were measured. Immunohistochemistry, RT-PCR, Western blot and confocal microscope were used to analyze the expression of HMGB1, RAGE, TLR4 and NF-kappaB. Experiment 3 was used to detect Tan II A's influence on BBB. The expressions of HMGB1, TLR4, RAGE and NF-kappaB were up-regulated in ischemic brain. Compared with pMCAO group, the expressions of these factors significantly decreased in Tan II A-H group, the neurologic deficit, infarct volume and brain water content were alleviated (P<0.05) and claudin-5 was predominantly expressed in brain capillaries. Tan II A protected the brain from damage caused by pMCAO; this effect may be through down-regulation of HMGB1, RAGE and TLR4, NF-kappaB and up-regulation claudin-5 expression.

Wang L ，Zhang X ，Liu L ，Cui L ，Yang R ，Li M ，Du W ... -  《-》

Neuroprotective effect of bicyclol in rat ischemic stroke: down-regulates TLR4, TLR9, TRAF6, NF-κB, MMP-9 and up-regulates claudin-5 expression.

Inflammatory damage aggravates the cerebral ischemic pathological process and may pave a new way for treatment. Bicyclol has been proved to elicit a series of biologic effects through its anti-inflammatory property in treating hepatitis and hepatic ischemic/reperfusion injury. Whether this protective effect applies to cerebral ischemic injury, we therefore investigated the potential neuroprotective role of bicyclol and the underlying mechanisms. Male Sprague-Dawley rats were randomly assigned to five groups: permanent middle cerebral artery occlusion (pMCAO), Vehicle (pMCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50 mg/kg), By-H (Vehicle+bicyclol 100 mg/kg) and Sham operated group. Bicyclol was administered intragastrically once a day for 3 days, after 1h of bicyclol pretreatment on the third day; rat brain ischemia was induced by pMCAO. Neurological deficit, infarct volume, and brain edema were measured at 24 h after stroke. Immunohistochemistry, Western blot and real-time quantitative PCR were used to detect the expression of TLR4, TLR9, TRAF6, NF-κB and MMP-9, claudin-5. Compared with pMCAO group, bicyclol significantly ameliorated neurological deficit, decreased infarct volume and edema, and down-regulated the expression of TLR4, TLR9, TRAF6, NF-κB and MMP-9 (P<0.05). Meanwhile, the expression of claudin-5 was increased (P<0.05). Bicyclol has neuroprotective effect on cerebral ischemia, and this protection may be through down-regulating TLR4, TLR9, TRAF6, NF-κB, MMP-9 and up-regulating claudin-5 expression.

Zhang J ，Fu B ，Zhang X ，Chen L ，Zhang L ，Zhao X ，Bai X ，Zhu C ，Cui L ，Wang L ... -  《-》

Neuroprotection of early and short-time applying atorvastatin in the acute phase of cerebral ischemia: down-regulated 12/15-LOX, p38MAPK and cPLA2 expression, ameliorated BBB permeability.

It has been proved that chronic administration and pre-treatment with atorvastatin could protect brain tissue against ischemic injury. However, little is known regarding the effect of atorvastatin in the acute phase of ischemic stroke. This study investigated the potential neuroprotective effects of atorvastatin and underlying mechanisms in vivo. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). Experiment 1 was used to evaluate time course expressions of 12/15-LOX, mitogen-activated protein kinase (MAPK), phosphorylated-p38MAPK (phospho-p38MAPK) and cytosolic phospholipase A2 (cPLA2) after cerebral ischemia, seven time points were included. Experiment 2 was used to detect atorvastatin's neuroprotection in the acute phase of ischemic stroke; atorvastatin was administered immediately after MCAO. Neurological deficit, brain water content and infarct size were measured at 24h after stoke. Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to analyze the expression of 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2. Experiment 3 was used to detect atorvastatin's influence on blood-brain barrier (BBB). 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2 were up-regulated after cerebral ischemia. Compared with MCAO group, atorvastatin dramatically reduced brain water content and infarct sizes, and the over-expressions of 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2 were significantly decreased in high dose group (20mg/kg, P<0.05). Meanwhile, extra-vascular IgG was not only reduced, but BBB permeability was also ameliorated. Atorvastatin protected brain from damage caused by MCAO at the early stage; this effect may be through down-regulation of 12/15-LOX, p38MAPK and cPLA2 expressions, and ameliorating BBB permeability.

Cui L ，Zhang X ，Yang R ，Wang L ，Liu L ，Li M ，Du W ... -  《-》

Atorvastatin protects rat brains against permanent focal ischemia and downregulates HMGB1, HMGB1 receptors (RAGE and TLR4), NF-kappaB expression.

Wang L ，Zhang X ，Liu L ，Yang R ，Cui L ，Li M ... -  《-》