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Biomedical subjects

C H Tator

Publications and source records attributed to C H Tator.

At least 19 recordsLinked to original sources

Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat.

Ependymal cells of the adult mammalian spinal cord exhibit stem/progenitor cell properties following injury. In the present study, we utilized intraventricular injection of 1,1'-dioctadecyl-6,6'-di(4-sulfophenyl)-3,3,3',3'-tetramethylindocarbocyanine (DiI) to label the ependyma lining the central canal to allow tracking of the migration of endogenous ependymal cells and their progeny after spinal cord injury (SCI). We developed a minimal injury model that preserved the integrity of the central canal and did not interfere with ependymal cell labeling. Three days following SCI, there was an 8.6-fold increase in the proliferative labeling index of the ependymal cells at the level of the needle track based on bromodeoxyuridine labeling, compared with 1 day post-injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells were not detected in the ependyma or surrounding gray matter, indicating that ependymal cells do not undergo apoptosis in response to minimal injury. Nestin was rapidly induced in the ependyma by 1 day and expression peaked by 7 days post-injury. We quantitated the number and distance of ependymal cell migration following minimal injury. The number of ependymal cells migrating from the region of the central canal increased by 3 days following minimal injury and DiI-labeled glial fibrillary acidic protein expressing cells were detected 14 days post-SCI, most of which migrated within 70 microm of the region of the central canal. These results show that a minimal SCI adjacent to the ependyma is sufficient to induce an endogenous ependymal cell response where ependymal stem/progenitor cells proliferate and migrate from the region of the central canal, differentiating primarily into astrocytes.

Animals↗

Endogenous and exogenous CNS derived stem/progenitor cell approaches for neurotrauma.

Neural stem/progenitor cells capable of generating new neurons and glia, reside in specific areas of the adult mammalian central nervous system (CNS), including the ependymal region of the spinal cord and the subventricular zone (SVZ), hippocampus, and dentate gyrus of the brain. Much is known about the neurogenic regions in the CNS, and their response to various stimuli including injury, neurotrophins (NFs), morphogens, and environmental factors like learning, stress, and aging. This work has shaped our current views about the CNS's potential to recover lost tissue and function post-traumatically and the therapies to support the intrinsic regenerative capacity of the brain or spinal cord. Recently, intensive research has explored the potential of harvesting, culturing, and transplanting neural stem/progenitors as a therapeutic intervention for spinal cord injury (SCI) and traumatic brain injury (TBI). Another strategy has focused on maximizing the potential of this endogenous population of cells by stimulating their recruitment, proliferation, migration, and differentiation in vivo following traumatic lesions to the CNS. The promise of such experimental treatments has prompted tissue and biomaterial engineers to implant synthetic three-dimensional biodegradable scaffolds seeded with neural stem/progenitors into CNS lesions. Although there is no definitive answer about the ideal cell type for transplantation, strong evidence supports the use of region specific neural stem/progenitors. The technical and logistic considerations for transplanting neural stem/progenitors are extensive and crucial to optimizing and maintaining cell survival both before and after transplantation, as well as for tracking the fate of transplanted cells. These issues have been systematically addressed in many animal models, that has improved our understanding and approach to clinical therapeutic paradigms.

Animals↗

Spinal injuries in Canadian ice hockey: documentation of injuries sustained from 1943-1999.

OBJECTIVES: Study objectives were: (a) to examine the causes and incidence of major spinal cord injuries sustained by ice hockey players; and (b) to add recently reported Canadian cases to the Canadian Ice Hockey Spinal Injury Registry to determine the effectiveness of prevention efforts. METHODS: The study was a review of questionnaires returned retrospectively by physicians and other sources reporting ice hockey related spinal injuries in Canada. Physicians reported on the mechanism of injury, vertebral level of injury, presence of neurologic deficit, type of event, and type of fracture. RESULTS: Between 1943 and 1999, 271 major spinal injuries were reported in Canadian ice hockey players, of which 49.0% occurred to players 16-20 years of age. Ontario has had a disproportionately large number of injuries compared to some provinces, especially Quebec. Of the spinal cord injuries, 65.8% resulted from colliding with the boards, and 36.6% were due to players being pushed or checked from behind. The recent survey shows that there has been a decline in the number of major spinal cord injuries in Canadian ice hockey, especially those causing paralysis due to checking or pushing from behind. CONCLUSIONS: Impact of the head with the boards after being checked or pushed from behind was the most common mechanism of spinal cord injury. Injury prevention programs are becoming effective in reducing the overall number of injuries, especially those due to checking from behind. Greater awareness of the occurrence and mechanisms of injury through educational programs and rules changes by organized hockey have reduced the annual incidence of catastrophic spinal injuries in Canadian ice hockey.

Adolescent↗

Conservative management of vestibular schwannomas - second review of a prospective longitudinal study.

Vestibular schwannomas have been traditionally managed with microsurgical removal and in recent years, stereotactic radiotherapy. However, there is a group of patients in whom a conservative management approach might represent a desirable alternative. The aim of this study was to determine the natural history and outcome following the conservative management of 72 patients with unilateral vestibular schwannomas. This is a prospective cohort review of a previously published group of patients [Clin. Otolaryngol. (2000) 25, 28-39] with unilateral vestibular schwannoma that were initially analysed at our institution in 1998 [Walsh R.M., Bath A.P., Bance M.L. et al., Clin. Otolaryngol. (2000) 25, 28]. The mean duration of follow-up was 80 months (range 52-242 months). All the patients in the study underwent serial magnetic resonance imaging (MRI) for assessment of tumour growth. Patients were deemed to have failed conservative management if there was evidence of rapid radiological tumour growth and/or increasing signs and symptoms, which necessitated active intervention. The mean tumour growth rate for the entire group at the second review was 1 mm/year (range -0.84-9.65 mm/year). The mean growth rate for cerebellopontine angle tumours (1.3 mm/year) was significantly greater than that of internal auditory canal (IAC) tumours (0 mm/year) (P = 0.005). The majority of tumours (87.14%) grew <2 mm/year. There was significant tumour growth seen in 38.9%, no or insignificant growth in 41.7%, and negative growth in 19.4%. Twenty-three patients (32%) failed conservative management at the second review. There was no difference in the outcome of these failed patients in comparison with patients who underwent primary treatment without a period of conservative management. The mean growth rate of tumours in patients that failed conservative management (3.1 mm/year) was significantly greater than that in patients who did not fail (0.2 mm/year) (P < 0.001). No factors predictive of tumour growth or failure of conservative management were identified. Hearing deterioration with pure tone averages (0.5, 1, 2, 3 kHz) and speech discrimination scores occurred irrespective of tumour growth. This prospective study further emphasizes the role of conservative management in selected cases of vestibular schwannomas. Tumours in this study confined to the IAC typically demonstrated minimal or no growth on serial MRI scanning. Regular follow-up with interval scanning is mandatory in all patients.

Adult↗

National Hockey League reported concussions, 1986-87 to 2001-02.

OBJECTIVES: To examine the longitudinal media reported rate of concussions in the National Hockey League (NHL) over the period 1986-87 to 2001-02. METHODS: All injury reports published in the weekly sports newspaper The Hockey News for the 16 seasons 1986-87 through 2001-02 were reviewed for reported concussions. The Hockey News reports are based on weekly injury reports released by the NHL, which derive from reports submitted to the league by individual team offices. RESULTS: Adjusted for changes in the number of teams and games per season over the 16 year study period, and expressed as: number of concussions per 1000 games, results by season (starting with 1986-87) were 4, 8, 7, 7, 5, 5, 7, 7, 6, 8, 13, 20, 30, 27, 30, 25. Comparing each season with the prior season, significant increases were reported in 1997-98 and 1998-99 (p < 0.05 and 0.025, respectively), with no change since 1998-99. CONCLUSIONS: The reported concussion rate in the NHL during the last five years is more than triple that of the previous decade. Bigger, faster players, new equipment and harder boards and glass have all theoretically increased the risk of concussion in the NHL in recent years. However, the abrupt increase and subsequent plateau in concussion rate since 1997 suggests that increased recognition and reporting may be primarily responsible for the apparent increase in incidence.

Body Constitution↗

Evaluation of the ThinkFirst Canada, Smart Hockey, brain and spinal cord injury prevention video.

OBJECTIVE: The ThinkFirst Canada Smart Hockey program is an educational injury prevention video that teaches the mechanisms, consequences, and prevention of brain and spinal cord injury in ice hockey. This study evaluates knowledge transfer and behavioural outcomes in 11-12 year old hockey players who viewed the video. DESIGN: Randomized controlled design. SETTING: Greater Toronto Minor Hockey League, Toronto Ontario. SUBJECTS: Minor, competitive 11-12 year old male ice hockey players and hockey team coaches. INTERVENTIONS: The Smart Hockey video was shown to experimental teams at mid-season. An interview was conducted with coaches to understand reasons to accept or refuse the injury prevention video. MAIN OUTCOME MEASURES: A test of concussion knowledge was administered before, immediately after, and three months after exposure to the video. The incidence of aggressive penalties was measured before and after viewing the video. RESULTS: The number of causes and mechanisms of concussion named by players increased from 1.13 to 2.47 and from 0.67 to 1.22 respectively. This effect was maintained at three months. There was no significant change in control teams. There was no significant change in total penalties after video exposure; however, specific body checking related penalties were significantly reduced in the experimental group. CONCLUSION: This study showed some improvements in knowledge and behaviours after a single viewing of a video; however, these findings require confirmation with a larger sample to understand the sociobehavioural aspects of sport that determine the effectiveness and acceptance of injury prevention interventions.

Attitude to Health↗

Strategies for recovery and regeneration after brain and spinal cord injury.

Current knowledge of the epidemiology and pathophysiology of neurotrauma and the key clinical and experimental strategies for promoting recovery and regeneration after brain and spinal cord trauma are reviewed. Brief overviews of the epidemiology and pathophysiology of neurotrauma are presented, and the key experimental and clinical treatments for the promotion of recovery and regeneration after brain and spinal cord trauma are discussed.

Brain Injuries↗

Calcium influx is necessary for optimal regrowth of transected neurites of rat sympathetic ganglion neurons in vitro.

The calcium ion serves many major roles in cellular processes, and therefore, its specific role in the regrowth of neurites after transection has been difficult to define. In the present study the effect of calcium on regrowth of transected rat superior cervical ganglion neurons in culture independent of its effects on neuronal survival was examined. Superior cervical ganglion neurons in culture for 10-14 days were preloaded with the calcium chelator 1,2 bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), and then the neurites were transected. The chelation of calcium inhibited the initiation of regrowth, and also decreased the number of branches in the regrowing neurite. In a second experiment, neurites were transected in zero calcium medium to eliminate calcium influx, and no regrowth was observed for up to 6h after transection. At this time the medium was changed to 1.8mM calcium, and the neurites showed regrowth 2h afterwards. After neurite transection in 1.8mM calcium there was a rise in calcium in the soma demonstrated with the calcium indicator dye Fluo-3 AM. This rise was attenuated with BAPTA-AM preloading or transection in zero calcium medium. Cultures were also grown in compartmented chambers which allowed isolation of the cell body from the neurite environment, and then the neurites were transected with the neurites in 1.8mM calcium medium, and the cell bodies immersed in zero calcium medium. Under these conditions the majority of neurons showed a marked delay of initiation of regrowth. From these data we suggest the following about mammalian neurite regrowth after transection. (1) Calcium is necessary for the initiation of regeneration. (2) Calcium entry at the cell body is necessary for optimal initiation of neurite regrowth. (3) Intracellular calcium is necessary for the branching of regrowing neurites.

Animals↗

Treatment of severe double spinal cord injuries.

This is a case report describing an injury--sustained by a 25-year-old man during a car accident, and characterized by fracture dislocation of the spine at the level of C7 and T4 accompanied by pulmonary contusion. He had an incomplete spinal cord lesion at the level of C7 and a complete lesion at the level of T4 (T4 ASIA A). Imaging of the spine showed three column fractures with ventral spinal cord compression at both levels. Discussants of this case comment on the concept of acute treatment of severe double spinal cord injuries, and present their chosen way of management in this particular case.

Accidents, Traffic↗

Death of rat sympathetic ganglion cells in vitro caused by neurite transection: effect of extracellular calcium.

Calcium entry into neurons secondary to excitotoxic insults is believed to cause neuronal death after trauma and ischemia, but the role of calcium influx in neuronal death after neurite transection independent of excitotoxicity has not been clearly defined. This study assesses the effect of variations in extracellular calcium concentration ([Ca2+]e) from 50 nM to 5 mM on cell death, in 14-day-old cultures of dissociated sympathetic neurons from the superior cervical ganglia of newborn rats. The neurites were transected with a custom-made injury device, and cell death was assessed with propidium iodide and fluorescence microscopy. We found that neurite transection caused a significant increase (p < 0.05) in cell death at all [Ca2+]e studies, but there was no significant difference in mortality at the various [Ca2+]e. Cell death significantly increased between 2 and 24 h postinjury at all three [Ca2+]e. Cell death increased with decreasing distance between the cell body and the transection site, and there was a significant decrease in mortality at distances greater than 0.66 mm, irrespective of the [Ca2+]e. These results suggest that influx of extracellular calcium is not responsible for posttransection cell death, suggesting that calcium release from internal stores or calcium-independent cell death mechanisms are triggered by neurite transection.

Animals↗

Management of hydrocephalus associated with vestibular schwannoma and other cerebellopontine angle tumors.

OBJECTIVE: Hydrocephalus (HCP) resulting from cerebellopontine angle (CPA) tumors is not rare. This retrospective study was designed to investigate the incidence of HCP and the clinical presentations, management options, and outcomes of HCP in 284 patients with CPA tumors. METHODS: A retrospective study of 284 consecutive patients with CPA tumors (mostly vestibular schwannomas) treated from 1985 to 1996 at Toronto Western Hospital managed by one surgical team consisting of a neurosurgeon and a neuro-otologist. RESULTS: Thirty-nine patients (13.7%) had radiographic and/or clinical evidence of HCP, 37 preoperatively and 2 postoperatively. Tumor type distribution was 33 vestibular schwannomas, 5 meningiomas, and 1 cavernous hemangioma. Only five patients (12%) had obvious obstruction at the fourth ventricular level. In 36 patients (92%), symptoms were mostly chronic and mild, consistent with normal pressure hydrocephalus. Multivariate analysis confirmed the strong association of tumor size and incidence of HCP (P < .0001). Four patients underwent permanent shunting before microsurgical tumor excision, mainly because of florid symptoms of HCP. Microsurgical tumor excision without preoperative shunting was performed in 23 patients, 5 of whom required postoperative shunting in the first 2 months after tumor excision. Eighteen patients (78%) did not need shunts after tumor resection. With regard to tumor size, the postoperatively shunted group did not differ from the patients who had surgery but did not require shunt treatment (P < 0.50). The remaining 10 patients with preoperative HCP received shunts as the only treatment (3 patients), stereotactic radiosurgery (3 patients), or expectant management (4 patients). Two other patients without preoperative HCP developed postoperative HCP and required shunts. Postoperatively, we observed a significant (P < 0.001) increase in the incidence of pseudomeningocele and a nonsignificant (P < 0.1) increase in cerebrospinal fluid leaks (rhinorrhea and/or otorrhea) in patients without shunts as compared with postoperative patients without HCP. The patients were followed after any treatment for a mean of 3.2 years (range, 6 mo-10 yr). Follow-up in the patients who had surgery but did not require a shunt revealed a 61% decrease in clinical symptoms related to HCP and a 75% decrease in radiographic signs of HCP. CONCLUSION: In the presence of HCP, operative resection of CPA tumors can be performed without permanent cerebrospinal fluid shunting. Precautionary measures to decrease the incidence of postoperative complications related to cerebrospinal fluid leak in patients with preoperative HCP include meticulous obliteration of any exposed air cells, including those around the internal auditory canal, accurate restoration of the dural barrier, and temporary lowering of intracranial pressure with a ventricular or lumbar drain. Patients with persistent symptomatic HCP after tumor excision should be treated with a ventriculoperitoneal shunt. Delaying this decision until the postoperative period is safe and avoids unnecessary shunting in the majority of patients.

Brain Neoplasms↗

A novel method for simultaneous anterograde and retrograde labeling of spinal cord motor tracts in the same animal.

Examination of repaired spinal cord tracts has usually required separate groups of animals for anterograde and retrograde tracing owing to the incompatibility of techniques such as tissue fixation. However, anterograde and retrograde labeling of different animals subjected to the same repair may not allow accurate examination of that repair strategy because widely variable results can occur in animals subjected to the same strategy. We have developed a reliable method of labeling spinal cord motor tracts bidirectionally in the same animal using DiI, a lipophilic dye, to anterogradely label the corticospinal tract and Fluoro-Gold (FG) to retrogradely label cortical and brainstem neurons of several spinal cord motor tracts in normal and injured adult rats. Other tracer combinations (lipophilic dyes or fluorescent dextrans) were also investigated but were less effective. We also developed methods to minimize autofluorescence with the DiI/FG technique, and found that the DiI/FG technique is compatible with decalcification and immunohistochemistry for several markers relevant for studies of spinal cord regeneration. Thus, the use of anterograde DiI and retrograde FG is a novel technique for bidirectional labeling of the motor tracts of the adult spinal cord with fluorescent tracers and should be useful for demonstrating neurite regeneration in studies of spinal cord repair.(J Histochem Cytochem 49:1111-1122, 2001)

Animals↗

Modeling axonal injury in vitro: injury and regeneration following acute neuritic trauma.

Traumatic injury to axons was modeled in vitro using sympathetic principal neurons from the rat superior cervical ganglion. Neurons were grown as a pure culture on collagen in parallel tracks, with cell somata confined to the center, and neurites occupying the periphery of the culture dish. Growing as fascicles on tracks, the neurites demonstrated periodic varicosities. Neuritic transection was reliably and reproducibly achieved with a motor driven rubber impactor injury device. During a period lasting at least 1 h, dieback involving the proximal neurites averaged 105 +/- 10 microm. This was followed by neurite regeneration, with the injured segment being traversed within 36 h at an average rate of regeneration of 595 +/- 15 microm/day. The distal neurite segments showed degenerative changes within 1 h following transection, with initial receding of neurites progressing to vacuolation, beading, blebbing, and eventual detachment from the underlying matrix. This in vitro model of axonal injury allows neuritic injury to be studied at the cellular and molecular levels, and also provides a unique opportunity to test potential neuromodulatory and neuroprotective strategies.

Acute Disease↗

The role of conservative management of vestibular schwannomas.

Although microsurgery is generally regarded as the conventional treatment of choice for most vestibular schwannomas, there remains a group of patients in whom a conservative management approach may be a desirable alternative. The aim of this study was to determine the natural history and outcome following the conservative management of 72 patients with unilateral vestibular schwannomas. The reasons for conservative management included poor general health, age, patient preference, small tumour size, minimal or no symptoms, and tumour in the only/better hearing ear. The mean duration of follow-up was 39.8 months (range 12-194 months). All patients underwent serial magnetic resonance imaging (MRI) for assessment of tumour growth. Patients were deemed to have failed conservative management if there was evidence of continuous or rapid radiological tumour growth and/or increasing symptoms or signs. The mean tumour growth rate, according to the 1995 guidelines of the American Academy of Otolaryngology/Head and Neck Surgery, was 1.16 mm/year (range: 0.75 9.65 mm/year). Approximately 83% of tumours grew at < 2 mm/year. Significant tumour growth was seen in 36.4%, no or insignificant growth in 50%, and negative growth in 13.6% of tumours. The growth rate of CPA tumours (1.4 mm/year) was significantly greater than that of IAC tumours (0.2 mm/year) (P = 0.001). Failure of conservative management, in which active treatment was required, occurred in 15.3%. The outcome of these patients appeared to be as favourable to a comparable group who underwent primary treatment, without a period of conservative management. The mean growth rate of tumours in patients who failed conservative management (4.2 mm/year) was significantly greater than that in patients who did not fail (0.5 mm/year) (P < 0.01). No factors predictive of tumour growth or failure of conservative management were identified. Deterioration of mean pure tone average (0.5, 1, 2, 3 kHz) and speech discrimination scores occurred regardless of whether radiological tumour growth was demonstrated or not. This study suggests that in a select number of cases of vestibular schwannoma, a conservative management approach may be appropriate. Regular follow-up with serial MRI is mandatory. Deterioration of auditory function occurs even in the absence of tumour growth.

Case-Control Studies↗

Action of locally administered NMDA and AMPA/kainate receptor antagonists in spinal cord injury.

NMDA or AMPA/kainate receptor antagonists have been shown to provide neuroprotection following in vitro spinal cord injury, but the mechanisms by which these agents improve behavioral recovery and protect axonal function remains unclear. We hypothesized that treatment of spinal cord injury with these drugs would attenuate glutamate excitatory transmission by blocking the effects of glutamate receptors at the injury site or would improve spinal cord blood flow. To test these hypotheses, we observed the effects of locally administered MK-801 (30 nmol) or NBQX (5 or 15 nmol) into the injured spinal cord on axonal conduction and post-traumatic ischemia of the cord. The outcome measures were multimodality evoked potentials and blood flow in an acute compression injury model in rats. We found that locally administered MK-801 or NBQX 15 min after spinal cord injury attenuated the amplitude, delayed the latency of sensory evoked potentials and increased the sensory conduction time across the injury site, but did not improve blood flow during the 4-h period of observation. These results demonstrate that the NMDA and non-NMDA receptor antagonists produced a blockade of glutamate excitatory transmission in the afferent pathways at the injury site. It is suggested that the neuroprotection provided by these agents following spinal cord injury is mediated through blockade of glutamate ionotropic receptors in the injured spinal cord, but is not related to improvement of SCBF.

Animals↗