u-0126 and Spinal-Cord-Injuries

Warm acupuncture (WA) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The current study attempted to explore the WA therapy on neuronal apoptosis of SCI and the relationship with the extracellular signal-regulated kinase (ERK) signaling pathway.. After WA treatment, the Basso, Beattie & Bresnahan locomotor rating scale (BBB scale) of SCI rats in the WA treatment was significantly raised from 7 to 14 days after SCI. WA and U0126 treatment significantly diminished apoptotic cells and preserved the neurons in the injured spinal cord. WA and U0126 treatment alleviated the production of inflammatory cytokines in the spinal cord. The distinct increase of p-ERK 1/2 induced by SCI was reversed in WA and U0126 treatment groups. WA and U0126 treatment augmented the level of Bcl-2 and reversed the elevated cleaved caspase-3 protein level after SCI.. Our study demonstrated that WA might be associated with the downregulation of the ERK signaling pathway. In summary, our findings indicated that WA promotes the recovery of SCI via the protection of nerve cells and the prevention of apoptosis. Meanwhile, the anti-apoptotic effect of WA might be associated with the downregulation of the ERK signaling pathway, which could be one of the mechanisms of WA in the treatment of SCI.

Topics: Acupuncture Therapy; Animals; Apoptosis; Caspase 3; Extracellular Signal-Regulated MAP Kinases; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Recovery of Function; Signal Transduction; Spinal Cord; Spinal Cord Injuries

The objective of this study was to investigate whether cytosolic phospholipase A2 (cPLA2 ), an important isoform of PLA2 that mediates the release of arachidonic acid, plays a role in the pathogenesis of spinal cord injury (SCI).. A combination of molecular, histological, immunohistochemical, and behavioral assessments were used to test whether blocking cPLA2 activation pharmacologically or genetically reduced cell death, protected spinal cord tissue, and improved behavioral recovery after a contusive SCI performed at the 10th thoracic level in adult mice.. SCI significantly increased cPLA2 expression and activation. Activated cPLA2 was localized mainly in neurons and oligodendrocytes. Notably, the SCI-induced cPLA2 activation was mediated by the extracellular signal-regulated kinase signaling pathway. In vitro, activation of cPLA2 by ceramide-1-phosphate or A23187 induced spinal neuronal death, which was substantially reversed by arachidonyl trifluoromethyl ketone, a cPLA2 inhibitor. Remarkably, blocking cPLA2 pharmacologically at 30 minutes postinjury or genetically deleting cPLA2 in mice ameliorated motor deficits, and reduced cell loss and tissue damage after SCI.. cPLA2 may play a key role in the pathogenesis of SCI, at least in the C57BL/6 mouse, and as such could be an attractive therapeutic target for ameliorating secondary tissue damage and promoting recovery of function after SCI.

Topics: Animals; Butadienes; Drug Delivery Systems; Enzyme Activation; Enzyme Inhibitors; Female; Gene Expression Regulation, Enzymologic; Gene Targeting; Group IV Phospholipases A2; Injections, Spinal; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Nitriles; Pilot Projects; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries

This study investigates the effects and underlying mechanism of magnetic stimulation on injury-induced migration of white matter astrocytes. Twenty-four adult healthy SD rats were selected to inject 0.5 ml of 1% ethidium bromide (EB) in PBS into the dorsal spinal cord funiculus on the left side at the T10-11 level to make located spinal cord injury models. Then they were randomly divided into four groups (A, B, C, and D). Groups A, B, C, and D were exposed to 1 Hz pulsed magnetic stimulation underwent 5-min sessions on 14 consecutive days at the following levels: 0T (Group A) 1.9x40% T (Group B); 1.9x80% T (Group C); 1.9x100% T (Group D). On day 14 after stimulation, the rats were killed and the expression of glial fibrillary acidic protein (GFAP), microtubule associated protein-2 (MAP-2), extracellular signal-regulated kinase1/2 (ERK1/2), and the volume of holes were detected with immunohistochemistry. Quantitative analysis of the expression of GFAP, MAP-2, and ERK1/2 were performed with the image analysis system. With the increase of magnetic stimulation intensity, the volume of hole decreased at day 14 (P<0.05). In lesion areas, the expression of GFAP and ERK1/2 could be seen, while that of MAP-2 did not change before and after magnetic stimulation. Significant difference was revealed in the expression of GFAP, ERK1/2 among the four groups. It was significantly higher in the magnetic stimulation groups than that in the control group (P<0.05). After magnetic stimulation, astrocytes migrated into the hole. U0126, a potent and selective MEK1/2 inhibitor, inhibited up-regulation of pERK1/2 which was stimulated by magnetic stimulation. These data indicate that magnetic stimulation increases the migratory capacity of reactive white matter astrocytes in the injured center nervous system, which may be associated with activation of MEK1,2/ERK mitogenic pathway.

Topics: Animals; Astrocytes; Brain; Butadienes; Cell Movement; Gene Expression Regulation, Enzymologic; Glial Fibrillary Acidic Protein; Magnetic Field Therapy; Magnetics; Male; Mice; Microtubule-Associated Proteins; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Nitriles; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Up-Regulation