Biomedical subjects

Michael G Fehlings

Publications and source records attributed to Michael G Fehlings.

58 records · Page 4Linked to original sources

PubMed2002

Development and characterization of a novel, graded model of clip compressive spinal cord injury in the mouse: Part 2. Quantitative neuroanatomical assessment and analysis of the relationships between axonal tracts, residual tissue, and locomotor recovery.

A detailed examination of the histopathological features of the clip compression injury in mice was performed to understand the relationships between neurological function and existing pathology of the spinal cord. Adult, female CD1 mice underwent three grades of extradural clip compression injury (3-g, 8-g, and 24-g FEJOTA mouse clips), transection, and sham injury at T3-4. Quantitative behavioural assessments were performed for 4 weeks following SCI. After 4 weeks, Fluoro-Gold was introduced caudal to the SCI site, at T9, and was retrogradely transported for 5 days to the origin of spared axons through the injury site. Counts of retrogradely labeled neurons in the brain-stem, midbrain, and sensory-motor cortex indicated that the number of intact descending axons that traversed the lesion decreased with increasing injury severity (F > 28; df = 4; p < 0.0001; one-way ANOVA). Independent linear correlation analyses were performed between indices of neurological recovery (BBB and IP test), counts of retrogradely labeled neurons and morphometric assessments of normal residual tissue at the injury epicenter. The BBB test correlated strongly with the amount of residual tissue at the injury epicenter (R = 0.945, df = 28, p < 0.0001). Counts of neurons retrogradely labeled with Fluoro-Gold were also strongly correlated with the BBB scores. The extrapyramidal (raphespinal, reticulospinal, vestibulospinal, and rubrospinal) tracts had Pearson correlation coefficients (R) of 0.814, 0.812, 0.813, and 0.747, respectively (df = 28, p < 0.0001). The pyramidal (corticospinal) tract had a correlation of R = 0.747, df = 28, p < 0.0001 with the BBB scores. The IP scores also correlated strongly with the persistence of extrapyramidal (raphespinal, reticulospinal, vestibulospinal and rubrospinal) tracts with correlation coefficients of 0.801, 0.782, 0.790, and 0.836, respectively (df = 28, p < 0.0001). These data indicate that the counts of retrogradely labeled neurons at the origin of distinct descending motor pathways are predictors of the variance of the functional recovery measured by the BBB and IP tests following spinal cord injury. In addition, we provide a detailed neuroanatomical study of clip compression injury in mice that can be used to study the molecular mechanisms of SCI in knockout and transgenic mice.

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PubMedDate not supplied

Proposal of a modified, treatment-oriented classification of odontoid fractures.

BACKGROUND CONTEXT: The classification scheme of odontoid fractures described by Anderson and D'Alonzo is the one most commonly used. However, uncertainty exists in the distinction between Type II and "shallow" Type III fractures. Moreover, fractures at the base of the odontoid (Anderson and D'Alonzo Type II) include a spectrum of injury patterns. PURPOSE: To modify the Anderson and D'Alonzo classification of odontoid fractures based on current clinical treatment options. STUDY DESIGN: Proposal of a modified classification system for odontoid fractures. METHODS: A more precise distinction between Type II and III fractures based on the presence/absence of C1-C2 facet involvement is proposed. A modified classification of Type II fractures based on fracture line obliquity, displacement and comminution is then proposed, because these are factors deemed to influence management. To evaluate the reproducibility of this classification, 52 odontoid fractures were reviewed and classified by four attending spine surgeons and three spine fellows. RESULTS: There was substantial agreement (at least five of seven respondents) in 70% of cases. The overall kappa value for the modified classification system was 0.48, indicating moderate agreement, and there were no differences in kappa values between attending spine surgeons and fellows. CONCLUSIONS: The reproducibility of this system was demonstrated by the moderate agreement observed when applied to odontoid fractures at our institution. The proposed utility of this system is its ability to guide clinical decision making in the treatment of odontoid fractures. Prospective application of this modified classification system and suggested treatment options is now required.

Classification↗

PubMedDate not supplied

Pathophysiology of cervical myelopathy.

BACKGROUND CONTENT: Cervical myelopathy is a group of closely related disorders usually caused by spondylosis or by ossification of the posterior longitudinal ligament and is characterized by compression of the cervical spinal cord or nerve roots by varying degrees and number of levels. The decrease in diameter of the vertebral canal secondary to disc degeneration and osteophytic spurs compresses the spinal cord and nerve roots at one or several levels, producing direct damage and often secondary ischemic changes. PURPOSE: Clinicians who treat cervical myelopathy cord injuries should have a basic understanding of the pathophysiology and the processes that are initiated after the spinal cord has been injured. STUDY DESIGN/SETTING: Literature review. METHODS: Literature review of human cervical myelopathy and clinically relevant animal models to further our understanding of the pathological mechanisms involved. RESULTS: The pathophysiology of cervical myelopathy involves static factors, which result in acquired or developmental stenosis of the cervical canal and dynamic factors, which involve repetitive injury to the cervical cord. These mechanical factors in turn result in direct injury to neurons and glia as well as a secondary cascade of events including ischemia, excitotoxicity, and apoptosis; a pathobiology similar to that occurring in traumatic spinal cord injury. CONCLUSIONS: This review summarizes some of the significant pathophysiological processes involved in cervical myelopathy.

Apoptosis↗

PubMedDate not supplied

Pharmacological approaches to repair the injured spinal cord.

Acute traumatic spinal cord injury (SCI) results in a devastating loss of neurological function below the level of injury and adversely affects multiple systems within the body. The pathobiology of SCI involves a primary mechanical insult to the spinal cord and activation of a delayed secondary cascade of events, which ultimately causes progressive degeneration of the spinal cord. Whereas cell death from the mechanical injury is predominated by necrosis, secondary injury events trigger a continuum of necrotic and apoptotic cell death mechanisms. These secondary events include vascular abnormalities, ischemia-reperfusion, glutamate excitotoxicity and disturbances in ionic homeostasis, oxidative cell injury, and a robust inflammatory response. No gold standard therapy for SCI has been established, although clinical trials with methylprednisolone (NASCIS II and III) and GM-1 ganglioside (Maryland and Sygen) have demonstrated modest, albeit potentially important therapeutic benefits. In light of the overwhelming impact of SCI on the individual, other therapeutic interventions are urgently needed. A number of promising pharmacological therapies are currently under investigation for neuroprotective abilities in animal models of SCI. These include the sodium (Na+) channel blocker riluzole, the tetracycline derivative minocycline, the fusogen copolymer polyethylene glycol (PEG), and the tissue-protective hormone erythropoietin (EPO). Moreover, clinical trials investigating the putative neuroprotective and neuroregenerative properties ascribed to the Rho pathway antagonist, Cethrin (BioAxone Therapeutic, Inc.), and implantation of activated autologous macrophages (ProCord; Proneuron Biotechnologies) in patients with thoracic and cervical SCI are now underway. We anticipate that these studies will harken an era of renewed interest in translational clinical trials. Ultimately, due to the multi-factorial pathophysiology of traumatic SCI, effective therapies will require combined approaches.

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