Protective Effects of Curcumin Against Paclitaxel-Induced Spinal Cord and Sciatic Nerve Injuries in Rats.

Paclitaxel (PTX) is an antineoplastic agent commonly used in the treatment of solid tumors and is known to cause dose-limiting peripheral neurotoxicity. This study was performed to evaluate the protective effect of curcumin (CUR) against PTX-induced spinal cord and sciatic nerve injuries in rats. The rats were administered PTX (2 mg/kg, BW) intraperitoneally for the first 5 consecutive days followed by administration of CUR (100 and 200 mg/kg, BW daily in corn oil) orally for 10 days. Our results showed that CUR significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-6, iNOS and GFAP whereas caused an increase in levels of Nrf2, HO-1 and NQO1 in the spinal cord and sciatic nerve of PTX-induced rats. In addition, CUR suppressed the activation of apoptotic and autophagic pathways by increasing Bcl-2 and Bcl-xL, and decreasing p53, caspase-3, Apaf-1, LC3A, LC3B and beclin-1 mRNA expression levels. The results showed that CUR also maintained the spinal cord and sciatic nerve histological architecture and integrity by both LFB staining and H&E staining. Immunohistochemical expressions of 8-OHdG, caspase-3 and LC3B in the PTX-induced spinal cord tissue were decreased after administration of CUR. Taken together, our findings demonstrated that CUR has protective effects on PTX-induced spinal cord and sciatic nerve injuries in rats.

An experimental electro-acupuncture study in treatment of the rat demyelinated spinal cord injury induced by ethidium bromide.

Oligodendrocyte precursor cells (OPCs) are one of the potential treating tools for multiple sclerosis (MS). Therefore, the cell number and differentiation of OPCs in a demyelinated spinal cord are crucial for improvement of reparative process. In the present study, we investigated whether "Governor Vessel (GV)" electro-acupuncture (EA) could efficiently promote increase in cell number and differentiation of OPCs into oligodendrocytes, remyelination and functional recovery in the demyelinated spinal cord. The spinal cord of adult Sprague-Dawley rats was microinjected with ethidium bromide (EB) at T10, to establish a demyelinated model. Six groups of animals were performed for the experiment. After 15 days EA treatment, neurotrophin-3 (NT-3) level and number of NG2-positive OPCs were significantly increased. Compared with the sham group, more NG2-positive OPCs were distributed between neurofilament (NF)-positive nerve fibres or closely associated with them in the lesion site and nearby tissue. In rats given longer EA treatment for 30 days, the number of adenomatous polyposis coli (APC)-positive oligodendrocytes was increased. Concomitantly, the number of newly formed myelins was increased. This was coupled by increase in endogenous oligodendrocyte involved in myelin formation. Furthermore, behavioural test and spinal cord evoked potential detection demonstrated a significant functional recovery in the EA+EB day 30 group. Our results suggest EA treatment can promote NT-3 expression, increase the cell number and differentiation of endogenous OPCs, and remyelination in the demyelinated spinal cord as well as the functional improvement of demyelinated spinal cord.

Magnetic stimulation influences injury-induced migration of white matter astrocytes.

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.

[Effects of high dose of dynorphin on NMDA receptor and NOS activities in spinal cord of rats].

OBJECTIVE: To elucidate the effects of N-methyl-D-aspartate(NMDA) receptor and nitric oxide synthase (NOS) activity in dynorphin (Dyn)-induced spinal cord injury. METHODS: The NMDA receptor activity was measured by radio-ligand of 3H-MK801. The constitutive and inducible NOS (cNOS and iNOS) activities were assayed by 3H-arginine conversion. RESULTS: In ventral samples, both 3H-MK801 binding and cNOS activity increased at 0.5 h and persisted for 48 h while iNOS activity enhanced at 4 h after intratheacal injection (i.t.) Dyn A(1-17) at dose of 20 nmol/L. However, the 3H-MK801 binding activity reduced significantly from 4 h to 24 h and cNOS activity did not change at the same time in dorsal samples. 7-nitroindozol (7-NI) and aminoguanidine (AG) inhibited the effects of Dyn A(1-17) (20 nmol/L) on 3H-MK801 binding and NOS activities in ventral samples. N-nitro-L-arginine methyl ester (L-NAME) did not affect the elevation of Dyn A(1-17) on NOS activities but caused 3H-MK801 binding activity reduction in ventral samples. CONCLUSIONS: NMDA-NOS pathway might play important role in Dyn spinal neurotoxicity. NOS inhibitors and Dyn might produce cooperative down-regulation on the function of NMDA-NOS pathway in dorsal cord.