Traumatic Brain Injury-Mediated Neuroinflammation and Neurological Deficits are Improved by 8-Methoxypsoralen Through Modulating PPARγ/NF-κB Pathway.

8-Methoxypsoralen (8-MOP) has anti-inflammatory, antioxidant and tissue-repairing abilities. Here, we probed the function and mechanism of 8-MOP in traumatic brain injury (TBI). The in-vivo TBI model was constructed in Sprague-Dawley (SD) rats using controlled cortical impact (CCI) surgery. In parallel, BV2 microglia and HT22 neurons were activated by lipopolysaccharide (LPS) to establish an in-vitro model. The modified neurological score (mNSS) and the Morris water maze experiment were employed to evaluate the rats' neurological functions. The rats' brain edema was assessed by the dry and wet method, and neuronal apoptosis in damaged brain tissues was monitored by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Nissl's staining. Immunohistochemistry (IHC) was applied to verify Iba1-microglial activation in brain lesions of rats. The expression of inflammatory cytokines in BV2 microglia and HT22 neurons in the injured lesion of TBI rats was examined by the enzyme-linked immunosorbent assay (ELISA). The levels of iNOS, COX2, TLR4, PPARγ, STAT3, and NF-κB in brain lesions, BV2 microglia and HT22 neurons were compared by Western blot. As a result, 8-MOP administration reduced inflammation and LPS-induced neuronal damage in BV2 microglia. In vivo, 8-MOP treatment relieved neurological deficits in TBI rats, improved cognitive, learning and motor functions and mitigated brain edema and neuroinflammation induced by TBI. Furthermore, LPS or TBI activated the NF-κB and STAT3 pathways and repressed the PPARγ expression. However, 8-MOP treatment attenuated NF-κB and STAT3 phosphorylation and elevated PPARγ levels. Hence, 8-MOP exerts neuroprotective and anti-inflammatory effects in TBI rats by modulating the PPARγ/NF-κB pathway.

Hui Y ，Zhao H ，Shi L ，Zhang H ... -  《-》

Parthenolide ameliorates neurological deficits and neuroinflammation in mice with traumatic brain injury by suppressing STAT3/NF-κB and inflammasome activation.

Traumatic brain injury (TBI) triggers a set of complex inflammation that results in secondary injury. Parthenolide (PTN) is a sesquiterpene lactone extracted from the herb Tanacetum parthenium (Feverfew) and has potent anti-inflammatory, anti-apoptosis and anti-oxidative stress effects in the central nervous system (CNS)-related diseases. This study focuses on investigating the potential neuroprotective effect of PTN on TBI and the related mechanism. Bv2 microglia, primary microglia were stimulated by LPS, and HT22 neuron cells were stimulated by OGD/R, and they were treated with different doses of PTN. The expression profiles of pro-inflammatory cytokines, proteins, oxidative stress mediators, STAT3/NF-κB pathway, inflammasomes were detected. Forty male/female C57BL/6 mice were randomly divided into the sham, PTN, TBI, and TBI + PTN groups (10 mice per group). A mouse TBI model was set up with a controlled cortical impact (CCI) device. The modified nerve severity score (mNSS) was implemented to check short-term neurological impairment in mice, and the mice's memory and learning were assessed by the Morris water maze test. The water content in the mice's brains was measured by the dry-wet method. Hematoxylin-eosin (H&E) staining, Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay were applied for neuronal apoptosis. PTN dramatically alleviated LPS-induced inflammation in microglia, and OGD-mediated neuronal apoptosis and oxidative stress. In addition, PTN repressed LPS- or OGD-modulated STAT3/NF-κB and NLR family pyrin domain containing 1 (NLRP1), NLRP3, NLR family CARD domain containing 4 (NLRC4) inflammasomes activation. Administering the STAT3 inhibitor Stattic or NF-κB inhibitor Bay 11-7082 attenuated PTN-mediated effects. In vivo, PTN treatment relieved neural function deficits, brain edema and neuron apoptosis and improved the memory and learning function of TBI mice. Additionally, PTN impeded microglial activation and reduced the production of pro-inflammatory cytokines in brain lesions of TBI mice. Furthermore, PTN hindered STAT3/NF-κB and inflammasome activation. PTN can curb microglial activation and neuron apoptosis by dampening the STAT3/NF-κB pathway, thus exerting neuroprotective effects in TBI mice.

Ding W ，Cai C ，Zhu X ，Wang J ，Jiang Q ... -  《-》

Electroacupuncture regulates microglial polarization via inhibiting NF-κB/COX2 pathway following traumatic brain injury.

Zhang XH ，Cui H ，Zheng SM ，Lu Y ，Yuan HW ，Zhang L ，Wang HH ，Du RS ... -  《-》

The AMPK-SIRT1-FoxO1-NF-κB signaling pathway participates in hesperetin-mediated neuroprotective effects against traumatic brain injury via the NLRP3 inflammasome.

Song H ，Ding Z ，Chen J ，Chen T ，Wang T ，Huang J ... -  《-》

Ovatodiolide protects ischemia-reperfusion-induced neuronal injury via microglial neuroinflammation via mediating SIRT1/NF-κB pathway.

Ovatodiolide (OVA), a bioactive substance extracted from the bioactive component of Anisomeles indica, is reported to be endowed with anti-inflammatory properties. Nonetheless, its function in ischemia-reperfusion (I/R)-induced neurological deficits and microglial inflammation remains unclear. A middle cerebral artery occlusion (MCAO) model was set up in SD rats, which were then dealt with varying doses of OVA. The rats' neurological functions were estimated at diverse periods postoperatively. The dry and wet method, triphenyl tetrazolium chloride (TTC) staining, and Nissl's staining were conducted to measure brain edema, cerebral infarction area and neuronal damage, respectively. Immunohistochemistry (IHC) was performed to detect neuronal apoptosis and microglial activation, and the profiles of inflammatory factors in the cerebral tissues were estimated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In-vitro assays were implemented on HT22 neuronal cells and BV2 microglia to elaborate the effect of OVA against oxygen-glucose deprivation (OGD)-mediated effects. OVA relieved HT22 cell apoptosis and eased inflammation in BV2 microglia, which were induced by OGD. OVA mitigated NF-κB phosphorylation in BV2 cells, whereas boosted SIRT1 expression. However, inhibiting SIRT1 abolished the anti-inflammatory effects of OVA in BV2 microglia under OGD stimulation. The condition medium (CM) of OGD-treated BV2 cells enhanced HT22 cell apoptosis and damage. OVA treatment in BV2 cells relieved BV2-mediated injury on HT22 cells, which was reversed by SIRT1 inhibitor. In-vivo results revealed that OVA dose-dependently attenuated I/R rats' neurological deficits, reduced brain edema, cerebral infarction area, neuronal apoptosis and microglial overactivation. Additionally, OVA inactivated the NF-κB pathway and up-regulated SIRT1 in the I/R rat model. OVA prevented rats from brain I/R damage by hampering neuronal apoptosis and microglial inflammation via the SIRT1-NF-κB pathway. The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

Hu C ，Zhang S ，Chen Q ，Wang R ... -  《-》