Quercetin attenuates inflammatory processes after spinal cord injury in an animal model.

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.

Quercetin administration after spinal cord trauma changes S-100 levels.

BACKGROUND: It has been shown previously that S-100beta levels in serum correspond with the severity of central nervous system (CNS) trauma. It also has been suggested that S-100beta in CNS tissue is involved in neuroprotection and neuroregeneration. We have previously shown that administration of quercetin results in improved motor function in an animal model of spinal cord trauma. METHODS: Mid-thoracic spinal cord compression injury was produced in adult male Wistar rats. Serum and tissue samples were acquired from quercetin-treated animals (25 micromol/kg) and saline controls at 6, 12 and 24 hours after the trauma. S-100beta levels were measured using a luminometric assay in the damaged tissue and in the serum of the animals. RESULTS: The increase in serum S-100beta levels seen in saline controls after spinal cord trauma was ameliorated in the quercetin-treated animals at all time points, although the difference to saline controls became statistically significant only at 24 hrs after the trauma. Compared to tissue S-100beta levels in healthy animals, values were significantly decreased in saline controls at all three time points, while they were decreased at 6 hrs and increased at both 12 and 24 hrs in quercetin-treated animals. At all three time points tissue S-100beta levels were significantly higher in quercetin-treated animals than in saline controls. CONCLUSIONS: Administration of quercetin results in modification of S-100beta levels in the setting of experimental spinal cord trauma. The kinetic patterns of the S-100beta fluctuations in serum and tissue suggest that post-traumatic administration of quercetin decreases the extent of CNS injury.

Can admission S-100beta predict the extent of brain damage in head trauma patients?

BACKGROUND: As has been shown previously, S-100beta levels in serum can be a useful predictor of brain damage after head trauma. This pilot study was designed to investigate whether urine samples, which are much easier to obtain, could be used for the same purpose instead of serum samples. METHODS: Ninety-six consecutive patients admitted with head trauma were recruited in the study. After exclusion of 54 patients, mostly because of significant additional trauma, S-100beta levels were analyzed in serum and urine of 42 patients using a luminometric assay. A range for normal values was established based on samples from ten healthy volunteers. RESULTS: S-100beta serum levels increased proportional to the severity of the head trauma, as had been previously shown by several other groups. In many patients, initial increases in urine S-100beta levels were seen later than in serum, after which the kinetics of S-100beta levels in urine seemed to follow that established for serum levels. S-100beta values in urine were on average about 54% lower in urine than in serum. CONCLUSIONS: S-100beta levels in urine obtained on admission to the hospital are not a good indicator for the extent of brain damage. However, urine S-100beta levels obtained at later time points might be a useful indicator for the development of secondary brain injury.

A Fourier transform infrared microspectroscopic imaging investigation into an animal model exhibiting glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a highly malignant human brain tumour for which no cure is available at present. Numerous clinical studies as well as animal experiments are under way with the goal being to understand tumour biology and develop potential therapeutic approaches. C6 cell glioma in the adult rat is a frequently used and well accepted animal model for the malignant human glial tumour. By combining standard analytical methods such as histology and immunohistochemistry with Fourier Transform Infrared (FTIR) microspectroscopic imaging and multivariate statistical approaches, we are developing a novel approach to tumour diagnosis which allows us to obtain information about the structure and composition of tumour tissues that could not be obtained easily with either method alone. We have used a "Stingray" FTIR imaging spectrometer to analyse and compare the compositions of coronal brain tissue sections of a tumour-bearing animal and those from a healthy animal. We have found that the tumour tissue has a characteristic chemical signature, which distinguishes it from tumour-free brain tissue. The physical-chemical differences, determined by image and spectral comparison are consistent with changes in total protein absorbance, phosphodiester absorbance and physical dispersive artefacts. The results indicate that FTIR imaging analysis could become a valuable analytic method in brain tumour research and possibly in the diagnosis of human brain tumours.

Quercetin promotes functional recovery following acute spinal cord injury.

We tested the hypothesis that quercetin, a potent Fe(2+)-chelating flavonoid, would decrease secondary damage following spinal cord trauma. MRI studies using the relaxation of the T1 proton signal caused by Fe(2+) ions and the dose-dependent reversal of this effect by addition of quercetin in aqueous solution were used to guide us to the dosage of quercetin to be used in animal experimentations. Forty-four male Wistar rats were used in two experimental series to test the hypothesis that administration of quercetin improves recovery of motor function after acute traumatic spinal cord injury. Animals were subjected to laminectomy and subjected to an extradural 40-g force clip compression for 5 sec at T7. Quercetin or saline was administered intraperitoneally 1 h after injury and then every 12 hr thereafter. Recovery of motor function was assessed using BBB scores at weekly intervals for 4 weeks. A dose of 2.5 micromoles quercetin/kg body weight did not result in significantly better functional outcome, whereas doses ranging from 5 to 100 micromoles quercetin/kg body weight resulted in a significantly better functional outcome with half or more of the animals walking, although with deficit; in contrast, no animals walked in the group of saline-treated animals. No significant differences in behavioral outcome were seen amongst the doses ranging from 5 to 100 micromol/kg, nor was there a difference if animals were treated for 4 or 10 days. Therapeutic outcome was coincident with more efficient iron clearance, suggesting that one possible mechanism whereby quercetin decreases secondary damage is through iron chelation.

Spinal angiolipoma.

BACKGROUND: Spinal epidural angiolipoma is a rare cause of spinal cord compression. We present a case and review the clinical presentation, radiological appearance, pathological aspects and treatment of this distinct clinico-pathological entity. METHODS: A case of a 46-year-old woman with a five-month history of progressive myelopathy affecting her lower extremities is presented. CT and MRI revealed a large epidural fat-containing mass compressing the spinal cord dorsally at the T7-T8 level. A laminectomy was performed with gross total resection of the lesion. RESULTS: The patient's neurologic symptoms improved postoperatively. A two-year follow-up period has revealed no signs of tumor recurrence and no neurological deficit. CONCLUSION: The diagnosis of spinal angiolipoma should be considered in the differential diagnosis of spinal cord compression. Magnetic resonance imaging is the investigation of choice. The surgical objective is complete excision but, for anterior lesions involving bone, an overly aggressive approach should be tempered by an awareness of the overall indolent natural history of so-called "infiltrating" spinal angiolipomas that are only partially excised.

Promoting glutathione synthesis after spinal cord trauma decreases secondary damage and promotes retention of function.

The study aimed to 1) quantify oxidative stress in spinal cord after crush injury at T6, 2) determine whether the administration of the procysteine compound L-2-oxothiazolidine-4-carboxylate (OTC) would up-regulate glutathione (GSH) synthesis and decrease oxidative stress, and 3) determine whether decreased oxidative stress results in better tissue and function retention. We demonstrate that spinal cord compression (5 s with a 50 g aneurysm clip) at T6 in rats results in oxidative stress that is extensive (significant increases in oxidative stress seen at C3 and L4) and rapid in onset. Indices of oxidative stress used were GSH content, protein carbonyl content, and inactivation of glutathione reductase. Administration of OTC resulted in a marked decrease in oxidative stress associated with a sparing of white matter at T6 (16+/-1.9% retained in OTC-treated animals vs. less than 1% in saline-treated). Behavioral indices in control, saline-treated, and OTC-treated animals after 6 wk were respectively: angle board scores (59 degrees, 32 degrees, and 42 degrees ), modified Tarlov score (7, 2.4, and 4.1), and Basso-Beattie-Bresnahan score (21, 5.3, and 12.9). We conclude that administration of OTC after spinal cord trauma greatly decreases oxidative stress and allows tissue preservation, thereby enabling otherwise paraplegic animals to locomote.

Malignant rhabdoid tumor of the central nervous system with subarachnoid dissemination.

A case of primary central nervous system malignant rhabdoid tumor is presented. Clinical, radiological, and histopathological findings are described in detail. Because of a relatively long clinical course after presentation, it was possible to assess the clinical and radiological response to different treatment modalities: surgery, chemotherapy, and radiotherapy. Despite the complete clinical and radiological response that was achieved after subtotal excision, two cycles of chemotherapy, and high-dose radiotherapy, the tumor recurred within 4 months of completion of the treatment, with wide subarachnoid dissemination. Radiotherapy treatment of whole cranial axis is recommended.

The importance of "accessory" outflow pathways in hydrocephalus after experimental subarachnoid hemorrhage.

This study evaluated the changes in pathways of cerebrospinal fluid (CSF) outflow that accompanied acute and compensated hydrocephalus in the rabbit. Intraventricularly injected 99mTc antimony sulfide was used as a tracer of outflow pathways, and specified structures were counted 12 to 24 hours after injection. Fifteen rabbits were divided into three groups: 1) an acutely hydrocephalic group in which 3 cisternal injections of blood were followed by a study of CSF pressure, ventricular size, and CSF outflow pathways 1 week after the last injection; 2) a control group treated according to the same protocol, except that sterile saline was injected instead of blood; and 3) a chronic group also treated according to the same protocol but in which the animals were maintained an average of 4 weeks after the last blood injection. Ventricular size was measured by computed digitation and expressed as an area ratio of ventricle to brain (VBR). In control animals, 11.8% of the injected colloid dosage was found in cranial perineural lymphatic channels, and 4.8% appeared in the spinal cord. The mean CSF pressure was 149 +/- 20.2 mm H20 (mean +/- SE) and the mean VBR was 0.040 +/- 0.003. In animals evaluated 1 week after subarachnoid injection, accessory cranial perineural lymphatic outflow decreased significantly to 3.4%, and spinal cord activity increased to 9.8% (P less than 0.05, two-tailed t-test). These animals were hydrocephalic and had CSF pressure of 247 +/- 25.1 mm H20 (mean +/- SE) and VBR of 0.083 +/- 0.009.(ABSTRACT TRUNCATED AT 250 WORDS)

The surgical treatment of childhood moyamoya disease.

Moyamoya disease is a progressive disorder, predominantly seen in childhood, that can cause severe permanent disability. The search for effective treatment has largely been unsuccessful in the past, but recent efforts at surgical intervention have shown promising results. The natural history of moyamoya disease, the options for treatment, and a series of patients from the Hospital for Sick Children in Toronto are reviewed. The results of surgical treatment are encouraging and the authors believe that it should be offered to all pediatric patients in the progressive stage of the disease.

Calcium deposits on CSF shunts. Clinical observations and ultrastructural analysis.

CSF shunts removed from seven patients 5-12 years after placement were studied. Examination in each case revealed gritty mineral deposits adherent to the external surface. The deposits were further analyzed by routine histology, spectroscopy and scanning electron microscopy. These results and the clinical consequences of this calcification are discussed. Microdefects in the tubing may contribute to delayed calcification of Silastic shunt tubing.

Congenital spinal cord tumors in children.

The paediatric spinal cord may host a wide variety of congenital tumors, the most common of which have been discussed. Although the majority of these lesions are benign their delayed diagnosis, serious infectious complications or associated congenital anomalies may expose the patient to life threatening morbidity or serious permanent disabilities. Prompt surgical management provides a cure in most instances, and the gratification of a neurologically intact child.