Robert Griebel

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 (1661.9% retained in OTC‐treated animals vs. less than 1% in saline‐treated). Behavioral indices in control, salinetreated, and OTC‐treated animals after 6 wk were respectively: angle board scores (59°, 32°, and 42°), 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.—Kamencic, H., Griebel, R. W., Lyon, A. W., Paterson, P. G., Juurlink, B. H. J. Promoting glutathione synthesis after spinal cord trauma decreases secondary damage and promotes retention of function. FASEB J. 15, 243–250 (2001)

Acute spinal cord injury in the rat: comparison of three experimental techniques

Three techniques to produce experimental spinal cord injuries in the rat are compared; 1) the weight dropping method, 2) the aneurysm clip compression method and 3) the extradural balloon compression method. In principle, different forces were used in technique one, while a constant force for different durations is maintained in techniques two and three. The relationship between these different types of injuries and subsequent clinical recovery was assessed quantitatively by the inclined plane method of Rivlin and Tator. The weight dropping technique was found unreliable for experimental spinal cord injury in the rat while the aneurysm clip compression technique resulted in consistent cord injuries with respect to subsequent clinical recovery. The extradural balloon compression method invariably resulted in complete recovery after three and five minutes but no recovery after seven minutes of 0.1 cc air inflated balloon compression of the cord indicating a steep dose--response curve. However, using a 0.2 cc air inflated balloon, no recovery was noted after one minute compression. The major factor in the pathogenesis of spinal cord injury produced by the weight dropping technique is believed to be mechanical, while both mechanical and vascular factors seem to operate in the clip and balloon compression techniques.

CSF shunt complications: an analysis of contributory factors

The complications arising from 195 shunting procedures are described and correlated with patient and operative variables. Neither the patients age, sex, type of hydrocephalus, length of surgery, nor the use of prophylactic antibiotics correlated significantly with subsequent shunt complications. However, the surgeon performing the procedure and the type of shunt used were highly significant correlates.

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.

Title comparison of primary and secondary spinal epidural abscesses: a retrospective analysis of 29 cases

BACKGROUND Spinal epidural abscesses (SEA) are uncommon. In certain regions their incidence is rising. Vague initial presentation may result in delayed diagnosis. Familiarity with SEA is imperative because if not treated expeditiously, they can have devastating neurologic sequelae. METHODS A retrospective analysis using analysis of variance (ANOVA) was performed on patients diagnosed with SEA between 1980 through 2000. The patients were assigned to one of the two defined groups: primary (PSEA) consisted of SEA alone; secondary (SSEA) included SEAs with vertebral osteomyelitis. Both groups were compared for factors including survival, age, diagnostic accuracy, etiology, hospitalization, management, and outcome. RESULTS Twenty-nine cases were identified. Four (23.7%) were PSEAs and 25 (86.2%) were SSEAs. Mean age (52.7 vs. 53.2 years) and mean duration of hospitalization (39.2 vs. 38.6 days) were comparable in both groups (p = 0.9). The admitting diagnosis was correct in 75% of PSEA and 20% of SSEA cases (p = 0.1). Staphylococcus aureus was present in 75% and 68%, respectively. In SSEA cases, 24% (n = 6) of the infections were consequent to spinal surgery. PSEA did not show a predilection for any level. Most (56%) cases of SSEA occurred at the lumbar levels. The entire PSEA group and 58.3% of the SSEA group underwent surgery (p = 0.06), 75% versus 40.9% had a good outcome for PSEA and SSEA, respectively. CONCLUSIONS PSEAs are very rare. Both groups have similar characteristics. Staphylococci remain the predominant etiologic agent. PSEAs are treated by surgery; SSEAs are managed surgically or conservatively.

Epilepsy surgery in the first 3 years of life: A Canadian survey

Objective:  To determine the clinical characteristics, surgical challenges, and outcome in children younger than 3 years of age undergoing epilepsy surgery in Canada.

Memory and survival after microbeam radiation therapy

BACKGROUND Disturbances of memory function are frequently observed in patients with malignant brain tumours and as adverse effects after radiotherapy to the brain. Experiments in small animal models of malignant brain tumour using synchrotron-based microbeam radiation therapy (MRT) have shown a promising prolongation of survival times. MATERIALS AND METHODS Two animal models of malignant brain tumour were used to study survival and memory development after MRT. Thirteen days after implantation of tumour cells, animals were submitted to MRT either with or without adjuvant therapy (buthionine-SR-sulfoximine=BSO or glutamine). We used two orthogonal 1-cm wide arrays of 50 microplanar quasiparallel microbeams of 25 microm width and a center-to-center distance of about 200 microm, created by a multislit collimator, with a skin entrance dose of 350 Gy for each direction. Object recognition tests were performed at day 13 after tumour cell implantation and in monthly intervals up to 1 year after tumour cell implantation. RESULTS In both animal models, MRT with and without adjuvant therapy significantly increased survival times. BSO had detrimental effects on memory function early after therapy, while administration of glutamine resulted in improved memory.

Hemorrhagic changes in experimental spinal cord injury models

Early hemorrhagic changes in the spinal cord were compared in three experimental spinal cord injury models in the rat in order to determine the nature and consistency of spinal cord hemorrhage following specific and quantitated forces of injury. The spinal cords were injured by weight-dropping, aneurysm clip and extradural balloon compression techniques. Hemorrhagic changes were assessed quantitatively by the image analyser at 1 and 3 hours after injury. Tissue damage was assessed by determining the percentage of total cross sectional area containing hemorrhage. The extent of hemorrhage at site of injury in the clip and balloon preparations was equal, but several times lower in the weight-drop induced injury. Within each experimental group no appreciable differences were observed at the site of injury between the 1 and 3 hours preparations. The variability of damage within experimental groups was most in the weight-dropping and balloon and least in the clip preparations. Differences were also indicated with respect to the distribution of hemorrhage in grey versus white matter. These findings may be of significance when functional recovery is considered in various experimental acute spinal cord injury models.

Propionibacterium acnes infections after cranial neurosurgery.

BACKGROUND Propionibacterium acnes (P. acnes) is a relatively avirulent organism that is part of the normal skin flora. Most patient isolates are considered contaminants but, in a small subset of patients, particularly in the post-neurosurgery setting, the organism can cause significant infections. We reviewed our experience with the occurrence and management of P. acnes infections after cranial neurosurgical procedures over a five-year period. METHODS Patients with positive cultures for P. acnes between 1996 and 2001 were identified by review of the Saskatoon Health Region microbiology laboratory database. Of the 141 positive cultures, a review of hospital records identified six patients with P. acnes infections after neurosurgical procedures. A review of the literature related to P. acnes associated CNS infections was conducted. RESULTS All patients had undergone a craniotomy or burrhole placement, and one patient had received prior radiotherapy. There were no P. acnes-related ventriculoperitoneal shunt infections. All patients presented with scalp swelling and three had purulent discharge. Symptoms occurred more than two months after the initial surgery in five of six patients, while one patient developed symptoms three years post-operatively. Management for all patients included removal of the craniotomy flap and treatment with parenteral antibiotics, followed in most cases by oral antibiotics. A good response without relapse of infection was seen in five patients; one patient had recurrent infection after cranioplasty. CONCLUSIONS P. acnes is a rare but important cause of infection after craniotomy. Wound debridement, removal of the bone flap and adequate antibiotic coverage result in cure in the majority of patients.

Expression of N-myristoyltransferase in human brain tumors.

N-myristoylation is a process of covalent irreversible protein modification that promotes association of proteins with membranes. Based on our previous findings of elevated N-myristoyltransferase (NMT) activity in colonic epithelial neoplasms that appears at an early stage in colonic carcinogenesis, together with elevated NMT expression in human colorectal and gallbladder carcinomas, we investigated NMT activity and protein expression of NMT1 and NMT2 in human brain tumors and documented elevated NMT activity and higher protein expressions. For the first time, we have demonstrated that NMT has the potential to be used as a marker of human brain tumors. However, further studies with larger number of patients are required to establish its role as a complementary diagnostic tool. This finding has significant implications for further understanding of biological mechanisms involved in tumorigenesis, as well as for diagnosis and therapy of human brain tumors.