GSH may prevent FFAs-induced HBVECs damage, oxidative stress, and apoptosis through activating the Akt pathway.

Previous studies have indicated that bone morphogenetic protein-7 (BMP-7) is neuroprotective against cerebral ischemia/reperfusion (IR) injury. The present study was undertaken to determine the molecular mechanisms involved in this effect. Adult male Wistar rats were subjected to 2 h of transient middle cerebral artery occlusion (MCAO), followed by 24 h of reperfusion. BMP-7 (10−4 g/kg) or vehicle was infused into rats at the onset of reperfusion via the tail vein. Neurological deficits, infarct volume, histopathological changes, oxidative stress-related biochemical parameters, neuronal apoptosis, and apoptosis-related proteins were assessed. BMP-7 significantly improved neurological and histological deficits, reduced the infarct volume, and decreased apoptotic cells after cerebral ischemia. BMP-7 also markedly enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reduced the level of malondialdehyde (MDA) in IR rats. In addition, Western blot analysis indicated that BMP-7 prevented cytochrome c release, inhibited activation of caspase-3, caspase-9 and caspase-8. Our data suggested that BMP-7 has protective effects against cerebral IR injury in rats, and the neuroprotective effects may be attributed to attenuating oxidative stress and inhibiting neuronal apoptosis.

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Granulocyte-colony stimulating factor (G-CSF) has been shown to play a neuroprotective role in ischemic stroke by mobilizing bone marrow (BM)-derived endothelial progenitor cells (EPCs), promoting angiogenesis, and inhibiting apoptosis. Impairments in mobilization and function of the BM-derived EPCs have previously been reported in animal and human studies of diabetes where there is both reduction in the levels of the BM-derived EPCs and its ability to promote angiogenesis. This is hypothesized to account for the pathogenesis of diabetic vascular complications such as stroke. Here, we sought to investigate the effects of G-CSF on diabetes-associated cerebral vascular defect. We observed that pretreatment of the cultured human brain vascular endothelial cells (HBVECs) with G-CSF largely prevented cell death induced by the combination stimulus with high glucose, free fatty acids (FFA) and hypoxia by increasing cell viability, decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by transmission electron microscope (TEM) revealed that G-CSF treatment nicely reduced combination stimulus-induced cell apoptosis. The results from fluorescent probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular calcium ions under combination stimulus. We also found that G-CSF enhanced the expression of cell cycle proteins such as human cell division cycle protein 14A (hCdc14A), cyclinB and cyclinE, inhibited p53 activity, and facilitated cell cycle progression following combination stimulus. In addition, activation of extracellular signal-regulated kinase1/2 (ERK1/2) and Akt, and deactivation of c-Jun N terminal kinase (JNK) and p38 were proved to be required for the pro-survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G-CSF is capable of alleviating HBVECs injury triggered by the combination administration with high glucose, FFA and hypoxia involving the mitogen-activated protein kinases (MAPK) and Akt signaling cascades. G-CSF may represent a promising therapeutic agent for diabetic stroke.

The effect of topical colchicine treatment of the sciatic nerve on sciatic and saphenous nociceptive thresholds and neurogenic extra-vasation was investigated in normal and neuropathic rats. After a pilot investigation using several different concentrations of colchicine it was determined that treating the sciatic nerve with 5 mM colchicine did not usually affect the heat nociceptive threshold over the sciatic innervated plantar surface of the hindpaw. Mechanical nociception and motor function were also unchanged. Electrical stimulation of the sciatic nerve after intravenous injection of Evans blue dye causes extravasation of the dye in the cutaneous distribution of the nerve. The area and quantity of sciatic extravasation were measured 3 weeks after treating the sciatic nerve with colchicine. This treatment results in a marked loss of neurogenic extravasation, but there were no changes in the sciatic and saphenous mediated heat and mechanical nociceptive thresholds. The area of saphenous nociceptive innervation was mapped using pinch responses and saphenous neurogenic extravasation acutely after sciatic section. There was no change in the cutaneous distribution of saphenous nociceptive fibers when measured 3 weeks after the sciatic colchicine treatment. Some rats had their sciatic nerves transected immediately after colchicine treatment (5 and 50 mM) and the saphenous nociceptive thresholds and autotomy scores were followed postoperatively. Colchicine pretreatment of the sciatic nerve has no effect on the development of hyperalgesia or autotomy. Colchicine blocks axonal transport in peripheral nerve, including the orthograde transport of tachykinins, which probably explains its ability to induce prolonged reductions in sciatic neurogenic extravasation at concentrations that spare C-fiber nociceptor function. Sciatic nerve colchicine treatment does not trigger nociceptive fiber collateral sprouting from the adjacent saphenous nerve, nor does it influence the development of hyperalgesia and autotomy behavior after sciatic transection.