Baincalein alleviates early brain injury after experimental subarachnoid hemorrhage in rats: possible involvement of TLR4/NF-κB-mediated inflammatory pathway.

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes. Hence, effective therapeutic strategies targeting on EBI have recently become a major goal in the treatment of SAH patients. Baicalein is a flavonoid that has been shown to offer neuroprotection in kinds of brain injury models. This study investigated the effects of baicalein on EBI in rats following SAH. SAH was inducted in male Sprauge-Dawley rats by injection of fresh non-heparinized arterial blood into the prechiasmatic cistern. Baicalein (30 or 100 mg/kg) or vehicle were administrated 30 min after injury. Neurological deficit, brain edema, blood-brain barrier (BBB) permeability and neural cell apoptosis were assessed. To explore the further mechanisms, the change of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) signaling pathway and the levels of apoptosis associated proteins were also examined. Our study showed that treatment with baicalein (30 mg/kg) significantly improved neurological function at 24h after SAH and reduced brain edema at both 24h and 72 h after SAH. Baicalein also significantly reduced neural cell death, BBB permeability. These changes were associated with the remarkable reductions of TLR4 expression, IκB-α degradation, NF-κB translocation to nucleus, as well as the expressions of matrix metalloproteinase-9, tight junctions protein, interleukin-1β and tumor necrosis factor- ɑ. These findings suggest that baicalein may ameliorate EBI after SAH potentially via inhibition of inflammation-related pathway.

Wang CX ，Xie GB ，Zhou CH ，Zhang XS ，Li T ，Xu JG ，Li N ，Ding K ，Hang CH ，Shi JX ，Zhou ML ... -  《-》

Fisetin alleviates early brain injury following experimental subarachnoid hemorrhage in rats possibly by suppressing TLR 4/NF-κB signaling pathway.

Early brain injury (EBI) determines the unfavorable outcomes after subarachnoid hemorrhage (SAH). Fisetin, a natural flavonoid, has anti-inflammatory and neuroprotection properties in several brain injury models, but the role of fisetin on EBI following SAH remains unknown. Our study aimed to explore the effects of fisetin on EBI after SAH in rats. Adult male Sprague-Dawley rats were randomly divided into the sham and SAH groups, fisetin (25mg/kg or 50mg/kg) or equal volume of vehicle was given at 30min after SAH. Neurological scores and brain edema were assayed. The protein expression of toll-like receptor 4 (TLR 4), p65, ZO-1 and bcl-2 was examined by Western blot. TLR 4 and p65 were also assessed by immunohistochemistry (IHC). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the production of pro-inflammatory cytokines. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) was perform to assess neural cell apoptosis. High-dose (50mg/kg) fisetin significantly improved neurological function and reduced brain edema at both 24h and 72h after SAH. Remarkable reductions of TLR 4 expression and nuclear factor κB (NF-κB) translocation to nucleus were detected after fisetin treatment. In addition, fisetin significantly reduced the productions of pro-inflammatory cytokines, decreased neural cell apoptosis and increased the protein expression of ZO-1 and bcl-2. Our data provides the evidence for the first time that fisetin plays a protective role in EBI following SAH possibly by suppressing TLR 4/NF-κB mediated inflammatory pathway.

Zhou CH ，Wang CX ，Xie GB ，Wu LY ，Wei YX ，Wang Q ，Zhang HS ，Hang CH ，Zhou ML ，Shi JX ... -  《-》

Pentoxifylline Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats: Possibly via Inhibiting TLR 4/NF-κB Signaling Pathway.

Xia DY ，Zhang HS ，Wu LY ，Zhang XS ，Zhou ML ，Hang CH ... -  《-》

Neuroprotective effect of Cyclosporin A on the development of early brain injury in a subarachnoid hemorrhage model: a pilot study.

Cyclosporin A (CsA) has been demonstrated to be neuroprotective in ischemic and traumatic brain injuries by inhibiting mitochondrial permeability transition pore (mPTP) opening, thereby maintaining mitochondrial homeostasis and inhibiting pro-apoptotic protein release. The effects of CsA on early brain injury (EBI) after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of CsA on apoptotic signaling pathways and EBI after experimental SAH using four equal groups (n=36) of adult male SD rats, including the sham group, SAH+vehicle group, SAH+CsA2 group, and SAH+CsA10 group. The rat SAH model was induced by injection of 0.3ml non-heparinized arterial blood into the prechiasmatic cistern. In the SAH+CsA2 and SAH+CsA10 groups, a dose of 2mg/kg and 10mg/kg CsA was directly administered by intercarotid injection at 15min and again 24h after SAH induction. Cerebral tissue samples were extracted 48h after SAH. Increased expressions of Cytochrome C, apoptosis-inducing factor (AIF), and cleaved caspase-3 were observed in the cerebral cortex after SAH. Treatment with high dose (10mg/kg) CsA markedly decreased expressions of Cytochrome C, AIF, and cleaved caspase-3, and inhibited apoptosis pathways. Administration of CsA following SAH significantly ameliorated EBI, including cortical apoptosis, brain edema, blood-brain barrier (BBB) impairment, and neurobehavioral deficits. These findings suggest that early administration of CsA may ameliorate EBI and provide neuroprotection in the SAH model through potential mechanisms that include blockage of mPTP opening and inhibition of apoptotic cell death pathways.

Xie Z ，Lei B ，Huang Q ，Deng J ，Wu M ，Shen W ，Cheng Y ... -  《-》

Hydrogen-Rich Saline Attenuated Subarachnoid Hemorrhage-Induced Early Brain Injury in Rats by Suppressing Inflammatory Response: Possible Involvement of NF-κB Pathway and NLRP3 Inflammasome.

Shao A ，Wu H ，Hong Y ，Tu S ，Sun X ，Wu Q ，Zhao Q ，Zhang J ，Sheng J ... -  《-》