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

No abstract

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.

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.

Diabetic peripheral neuropathic pain (DPNP) is a common and intractable complication of diabetes. Conventional therapies are always not ideal; development of novel drugs is still needed to achieve better pain relief. Recent evidences have demonstrated that inflammation is involved in the onset and maintenance of DPNP. The anti-inflammatory property of Tanshinone IIA (TIIA) makes it a promising candidate to block or alter the pain perception. This study was conducted to investigate whether TIIA could attenuate DPNP in streptozotocin- (STZ-) induced rats model and its potential mechanisms. TIIA was administered to STZ-induced diabetic rats at the dose of 40 mg/kg once a day for 3 weeks. The effects of TIIA on thermal hyperalgesia and mechanical allodynia were investigated using behavioral tests. The mRNA level and expression of interleukin- (IL-) 1β, interleukin- (IL-) 6, tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 10 in the fourth to sixth segments of the dorsal root ganglion (L4–6 DRG) were detected by quantitative real-time PCR (qPCR) and Western blot. TIIA treatment significantly attenuated mechanical allodynia and thermal hyperalgesia in diabetic rats. In addition, the expression of the proinflammatory cytokines IL-1β, IL-6, and TNF-α was inhibited, and the level of the anti-inflammatory cytokine IL-10 was increased by TIIA. This study demonstrated that TIIA has significant antiallodynic and antihyperalgesic effects in a rat model of STZ-induced DPNP, and the effect may be associated with its anti-inflammation property.

This suggests that microvascular decompression is effective in adolescent-onset idiopathic hemifacial spasm.

Diabetic peripheral neuropathic pain (DPNP) is a common manifestation of diabetic peripheral neuropathy (DPN). Although the pathogenesis of DPNP remains unclear, the disinhibition of spinal dorsal horn neuronal circuitry mediated by endoplasmic reticulum stress (ERS) is an important mechanism underlying neuropathic pain (NP). Tanshinone II A is mainly used to treat cardiovascular diseases but has also been shown to relieve various types of neuralgia, including DPNP. This study investigated the effects of tanshinone II A in DPNP model rats. We divided animals into two groups: 1) the model (diabetic) group and 2) the tanshinone II A-treatment group. Our results demonstrated that diabetic rats exhibited a decrease in the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), and that NMT is increased and TWL is prolonged in rats treated with tanshinone II A. Additionally, the levels of ERS-signaling pathway factors in the spinal dorsal horns of rats were lower in the tanshinone II A-treated group than in the diabetic group. Overall, our study demonstrated that the disinhibition of spinal dorsal horn neuronal circuitry mediated by endoplasmic reticulum stress underlies DPNP and is modulated by tanshinone II A treatment.