In vivo microdialysis of glutamate in ventroposterolateral nucleus of thalamus following electrolytic lesion of spinothalamic tract in rats.

Central pain is one of the most important complications after spinal cord injury (SCI), and thereby, its treatment raises many challenges. After SCI, in a cascade of molecular events, a marked increase in glutamate at the injury site results in secondary changes which may impact on supraspinal regions, mainly ventroposterolateral (VPL). There is little information about the changes in glutamate metabolism in the VPL and whether it contributes to SCI-related central pain. The present study was performed to evaluate glutamate release in the VPL following electrolytic lesion of spinothalamic tract (STT). A laminectomy was performed at spinal segments of T9-T10 in male rats, and then, unilateral electrolytic lesions were made in the STT. Glutamate concentrations in ipsilateral VPL dialysate were measured by HPLC method at days 3, 7, 14, 21 and 28 post-injury. Tactile pain and motor activity were also examined. Glutamate levels were significantly increased in ipsilateral VPL of spinal-cord-injured rats 2 weeks after SCI and remained high up to day 28 post-surgery. The STT lesions had no marked effect on our measures of motor activity, but there was a significant decrease in paw withdrawal threshold in the hind paws at day 14 post-SCI. These findings suggest that an increased release of glutamate in VPL plays a role in secondary pathologic changes, leading to neuronal hyperexcitation and neuropathic pain after SCI.

Therapeutic effects of a combinatorial treatment of simvastatin and bone marrow stromal cells on experimental embolic stroke.

In this study, we investigated the therapeutic effects of simvastatin administered in combination with bone marrow stromal cells (BMSCs) following experimentally induced embolic stroke in rats. Effects on infarct volume, brain oedema and neurological deficits were examined. Focal ischaemic brain injury was induced by emblazing a preformed clot into the middle cerebral artery in rats. Animals were administered simvastatin (40 mg/kg) at 1 hr after stroke, or BMSCs (3 × 10(6)) at 24 hr after stroke or a combination of these two treatments. Rats receiving a dose of simvastatin in combination with BMSC administration demonstrated a significant reduction in neurological deficits, a significant reduction in infarct volume and a significant decrease in brain oedema. Our data show that combining simvastatin administration with BMSCs has an additive effect on improving functional outcome in this thromboembolic stroke model.