ABSTRACT
Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Male mice were administered berberine (25, 50 mg/kg/d, intragastric; i.g.), glycyrrhizin (50 mg/kg/d, intraperitoneal), or berberine (50 mg/kg/d, i.g.) plus glycyrrhizin (50 mg/kg/d, intraperitoneal) for 14 consecutive days before tMCAO. The neurological deficit scores were evaluated at 24 h after tMCAO, and then the mice were killed to obtain the brain samples. We showed that pretreatment with berberine dose-dependently decreased the infarct size, neurological deficits, hispathological changes, brain edema, and inflammatory mediators in serum and ischemic cortical tissue. We revealed that pretreatment with berberine significantly enhanced uptake of 18F-fluorodeoxyglucose of ischemic hemisphere comparing with the vehicle group at 24 h after stroke. Furthermore, pretreatment with berberine dose-dependently suppressed the nuclear-to cytosolic translocation of high-mobility group box1 (HMGB1) protein, the cytosolic-to nuclear translocation of nuclear factor kappa B (NF-κB) and decreased the expression of TLR4 in ischemic cortical tissue. Moreover, co-administration of glycyrrhizin and berberine exerted more potent suppression on the HMGB1/TLR4/NF-κB pathway than berberine or glycyrrhizin administered alone. These results demonstrate that berberine protects the brain from ischemia-reperfusion injury and the mechanism may rely on its anti-inflammatory effects mediated by suppressing the activation of HMGB1/TLR4/NF-κB signaling.
Subject(s)
Berberine/therapeutic use , HMGB1 Protein/antagonists & inhibitors , Infarction, Middle Cerebral Artery/drug therapy , NF-kappa B p50 Subunit/antagonists & inhibitors , Neuroprotective Agents/therapeutic use , Reperfusion Injury/drug therapy , Animals , Brain/pathology , Brain Edema/drug therapy , Down-Regulation , Glycyrrhizic Acid/therapeutic use , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Infarction, Middle Cerebral Artery/etiology , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Male , Mice, Inbred C57BL , NF-kappa B p50 Subunit/genetics , NF-kappa B p50 Subunit/metabolism , Reperfusion Injury/complications , Signal Transduction/drug effects , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
To observe the morphology character of the anterior epidural space at the L4-5 disc level and to provide an anatomical basis for safely and accurately performing a percutaneous endoscopic lumbar discectomy (PELD). Fifty-five cases with L5 S1 lumbar disc herniation were included in this study, and cases with L4-5 disease were excluded. When the puncture needle reached the epidural space at the L5 S1 level, iohexol was injected at the pressure of 50 cm H2 O during the PELD, then C-Arm fluoroscopy was used to obtain standard lumbar frontal and lateral images. The widths of epidural space at the level of the L4 lower endplate, the L5 upper endplate, as well as the middle point of the L4-5 disc were measured from the lumbar lateral X-ray film. Epidural space at the L4-5 disc plane performs like a trapezium chart with a short side at the head end and a long side at the tail end in the lumbar lateral X-ray radiograph, while the average widths of epidural space were 10.2 ± 2.5, 12.3 ± 2.3, and 13.8 ± 2.6 mm at the upper, middle, and lower level of the L4-5 disc. Understanding the morphological characteristics of epidural space will contribute to improving the safety of the tranforaminal percutaneous endoscopy technique.
