Cerebral ischemia,brain tumor,and spinal cord injury (SCI) are the central nerve disease which usually cause irreversible,severe neurologic deficits or death.Inflammation plays a key role in the associated secondary damage after central nervous system (CNS) injury.Epidermal growth factor receptor (EGFR) excessive activation has been closely implicated in the initiation and progression of inflammation.Previous studies have shown that through depressing CNS inflammation,EGFR inhibitors may play a role in the therapeutic treatment of CNS disorders.We mainly reviewed the mechanisms of EGFR signaling pathway activation mediating inflammatory damage in CNS.

Objective: To characterize the microenvironment following blood-spinal cord barrier (BSCB) damage and to evaluate the role of BSCB disruption in secondary damage of spinal cord injury (SCI). Methods: A model of BSCB damage was established by co-culture of primary microvascular endothelial cells and glial cells obtained from rat spinal cord tissue followed by oxygen glucose deprivation/re-oxygenation (OGD/R). Permeability was evaluated by measuring the transendothelial electrical resistance (TEER) and the leakage test of Fluorescein isothiocyanate-dextran (FITC-dextran). The expression of tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1) were evaluated by Western blot and immunofluorescence microscopy. Proinflammatory factors (TNF-alpha, iNOS, COX-2 and IL-1 beta), leukocyte chemotactic factors (MIP-l alpha, MIP-1 beta) and leukocyte adhesion factors (ICAM-1, VCAM-1) were detected in the culture medium under different conditions by enzyme-linked immuno sorbent assay (ELISA). Results: The model of BSCB damage induced by OGD/R was successfully constructed. The maximum BSCB permeability occurred 6-12 hours but not within the first 3 h after OGD/R-induced damage. Likewise, the most significant period of TJ protein loss was also detected 6-12 hours after induction. During the hyper-acute period (3 h) following OGD/R-induced damage of BSCB, leukocyte chemotactic factors and leukocyte adhesion factors were significantly increased in the BSCB model. Pro-inflammation factors (TNF-alpha, IL-1 beta, iNOS, COX-2), leukocyte chemotactic factors (MIP-1 alpha, MIP-1 beta) and leukocyte adhesion factors (ICAM-1, VCAM-1) were also sharply produced during the acute period (3-6 hours) and maintained plateau levels 6-12 hours following OGD/R-induced damage, which overlapped with the period of BSCB permeability maximum. A negative linear correlation was observed between the abundance of proinflammatory factors and the expression of TJ proteins (ZO-1 and occludin) and transepithelial electrical resistance (TEER), and a positive linear correlation was found with transendothelial FITC-dextran. Conclusions: Secondary damage continues after primary BSCB damage induced by OGD/R, exhibiting close ties with inflammation injury.

BACKGROUND AND PURPOSE The amelioration of insulin resistance by bilobetin is closely related to its hypolipidaemic effect. The aim of the present study was to determine the insulin‐sensitizing mechanism of bilobetin by elucidating its effect on lipid metabolism.EXPERIMENTAL APPROACH Rats fed a high‐fat diet were treated with bilobetin for either 4 or 14 days before applying a hyperinsulinaemic–euglycaemic clamp. Triglyceride and fatty acids labelled with radioactive isotopes were used to track the transportation and the fate of lipids in tissues. The activity of lipid metabolism‐related enzymes and β‐oxidation rate were measured. Western blot was used to investigate the phosphorylation, translocation and expression of PPARα in several tissues and cultured cells. The location of amino acid residues subjected to phosphorylation in PPARα was also studied.KEY RESULTS Bilobetin ameliorated insulin resistance, increased the hepatic uptake and oxidation of lipids, reduced very‐low‐density lipoprotein triglyceride secretion and blood triglyceride levels, enhanced the expression and activity of enzymes involved in β‐oxidation and attenuated the accumulation of triglycerides and their metabolites in tissues. Bilobetin also increased the phosphorylation, nuclear translocation and activity of PPARα accompanied by elevated cAMP level and PKA activity. Threonine‐129–alanine and/or serine‐163–alanine mutations on the PPARα genes and PKA inhibitors prevented the effects of bilobetin on PPARα. However, cells overexpressing PKA appeared to stimulate the phosphorylation, nuclear translocation and activity of PPARα.CONCLUSIONS AND IMPLICATIONS Bilobetin treatment ameliorates hyperlipidaemia, lipotoxicity and insulin resistance in rats by stimulating PPARα‐mediated lipid catabolism. PKA activation is crucial for this process.

With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic encephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cognitive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronal loss and damaged cognitive functions. Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system, hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide deficiency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients. Those findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.