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Objectives:We have shown earlier that administration of the flavonoid quercetin significantly contributed to recovery of motor function after spinal cord compression injury in the adult rat. Using the same animal model, we have now designed a set of experiments to test the hypothesis that quercetin attenuates oxidative stress-related inflammatory processes early after spinal cord trauma.Methods:Mid-thoracic spinal cord compression injury in adult male Wistar rats was caused by extradural application and closure of a 50 g calibrated aneurysm clip for 5 s. Myeloperoxidase (MPO) levels were determined in spinal cord tissue and serum of quercetin-treated animals and controls at 6, 12, 24 and 72 h after injury. The white blood count was followed until 72 h after injury.Results:In quercetin-treated animals, MPO activity was significantly decreased in tissue at 12 and 24 h and in serum at 6, 12 and 24 h after injury, compared with saline controls. In quercetin-treated animals, the prevalence of ED-1 and MPO positive cells was significantly lower than in saline controls. White blood count in venous blood was significantly decreased in quercetin-treated animals at 12 and 24 h after injury.Conclusion:Quercetin attenuated the recruitment of neutrophils to the site of injury. The resulting lower MPO release in the injured tissue is likely to decrease the extent of secondary injury and might at least partially explain the neuroprotective effect of the flavonoid quercetin. [ABSTRACT FROM AUTHOR]

Objectives:We have shown previously that administration of quercetin after spinal cord injury in a rat model induced significant recovery of motor function. In the same model for spinal cord compression injury, we now have correlated the treatment duration with the extent to which motor function is recovered.Methods:Seventy-four male Wistar rats were assigned to eight experimental groups. Mid-thoracic spinal cord injury was produced in the animals of seven groups. Quercetin was administered intraperitoneally in individual doses of 25 μmol kg−1. Treatment onset was 1 h after the injury. The length of treatment ranged from one single injection to 10 days, with injection frequencies of two or three times daily. BBB (Basso, Beattie and Bresnahan) scores were obtained and tissue preservation at the site of injury was analyzed.Results:None of the untreated control animals recovered motor function sufficient to walk. When quercetin was administered twice daily over a period of either 3 or 10 days, about 50% of the animals recovered sufficient motor function to walk. Stepping/walking (BBB 10) were seen in two of six animals receiving only a single injection and in one of the six animal receiving three injections. Surprisingly, none of the animals that received quercetin injections three times daily recovered the ability to walk (all BBB 9).Conclusion:Quercetin administration results in preservation of tissue bridges at the site of injury. Treatment success depends on frequency of administration and overall dose. [ABSTRACT FROM AUTHOR]

Abstract: We have developed an X-ray imaging protocol that permits 3D visualisation of a small number of implanted cells within bulk tissue. The cells are marked using natural endocytosis of inert gold nano-particles. The resulting local increase in electron density allows high imaging contrast to be obtained from small clusters of these marked cells. Using this technique we have imaged C6 glioma cells within the brain of a model animal. The cells were marked by exposing them to colloidal gold incorporated in the growth media. Gold-loaded glioma cells were implanted into the brains of adult male Wistar rats. After tumours had been allowed to develop for up to 2 weeks, the animals were sacrificed and images of the intact cranium were acquired at the SYRMEP imaging station on the Elettra synchrotron in Italy. Computed tomography was performed using mixed absorption and phase contrast techniques at an X-ray energy of 24keV. In the resulting volume datasets the tumour bulk is clearly visible and the infiltrating nature of the malignant growth is well demonstrated. Although the protocol was developed using this particular model of malignant brain tumour, it is believed that it will be possible to use it with other cell lines. [Copyright &y& Elsevier]

Seizures are a well-recognized symptom of glioblastoma, and anticonvulsive treatment is common. While clinical guidelines recommend all approved anticonvulsants, so far there is a lack of data that allow a well-founded differential therapy. Based on pathophysiological knowledge about both mechanisms of glioma-associated seizures and tumor progression, it is conceivable that some certain anti-seizure medication could be more preferable than others in the sense of a combined anti-convulsive and anti-tumoral efficacy. Thus, glioma cells release glutamate via the Xc − antiport system, which appears to be a major pathomechanism of glioma-associated seizures and excitotoxicity. In addition, the proliferation and survival of the tumor cells are promoted. Therefore, anticonvulsants that attenuate glutamate-mediated receptor activation could be especially effective. In a first in vitro approach, perampanel had antiproliferative effects. In addition, AMPA receptor-mediated epileptiform activity was effectively reduced in rat glioma brain slices using perampanel. In our current studies, rat glioma cells are injected orthotopically into the neocortex of Fischer rats. Thus, both tumor disease and glioma-associated epilepsy can be simulated in a clinically relevant in vivo model. In this model, the efficacy of perampanel in combination with standard radio-chemotherapy on the survival of the animals is examined. Epileptiform activity is recorded with video EEG monitoring in vivo and additionally analyzed in an in vitro epilepsy model (Mg 2+ withdrawal, GABAA receptor inhibition). On the side of the tumor disease, the morphology of the gliomas is determined and the expression of relevant proteins is quantified. To gain further insights into the mechanisms of glutamate-mediated pathophysiology of human gliomas, patient-generated low-passage glioblastoma cell lines were established from more than 50 surgical brain tumor resectants. In 15 of these cell lines, we quantified the expression of various epilepsy-associated genes by RT-PCR. As expected, the genes SLC7A11, EAAT2, GLUL, BCAT1 and IDH1 were expressed differently in the cells. To validate these findings, four cell lines with a pro-epileptogenic phenotype were selected. In addition, the efficacy of perampanel on glutamate release and cell proliferation was tested. It could be shown that perampanel mediate an overall reduction of glutamate release cross all cell lines. With our combined in vitro and in vivo approach, we aim to investigate the efficacy of glutamate receptor antagonists such as perampanel on glioblastoma cells with respect to seizure development and tumor progression. Our results suggest that anticonvulsants that inhibit glutamate receptor activation may be particularly suitable. [ABSTRACT FROM AUTHOR]