Immunohistochemical Profile of NF-κB/p50, NF-κB/p65, MMP-9, MMP-2, and u-PA in Experimental Cervical Spondylotic Myelopathy

Karadimas, Spyridon K.; Klironomos, George; Papachristou, Dionysios J.; Papanikolaou, Sofia; Papadaki, Eleni; Gatzounis, George

doi:10.1097/brs.0b013e318261ea6f

Cited by 38 publications

(27 citation statements)

References 47 publications

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“…Moreover, MMP-9 has been implicated in promoting blood-brain barrier disruption and subsequent exaggeration of the inflammatory process in different CNS diseases. Interestingly, a recent study on a new rabbit model of CSM (Klironomos and others 2011) revealed that the MMP-9 immunoreactivity was significantly higher in spinal cord tissue from rabbits that underwent chronic compression of the cervical spinal cord for 20 weeks (Karadimas and others 2012a). Unfortunately, these authors did not evaluate the role of MMP-9 under the chronic progressive compression of the cervical spinal cord by blocking or deleting MMP-9.…”

Section: Current Knowledge In Cervical Spondylotic Myelopathy Pathobimentioning

confidence: 99%

Cervical Spondylotic Myelopathy

Kalsi-Ryan

Karadimas

Fehlings³

2012

Neuroscientist

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330

142

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Cervical spondylotic myelopathy (CSM) is a common disorder involving chronic progressive compression of the cervical spinal cord due to degenerative disc disease, spondylosis, or other degenerative pathology. CSM is the most common form of spinal cord impairment and causes functional decline leading to reduced independence and quality of life. Despite a sound understanding of the disease process, clinical presentation and management, a universal definition of CSM and a standardized index of severity are not currently used universally. Work is required to develop a definition and establish clinical predictors of progression to improve management of CSM. Despite advances in decompressive and reconstructive surgery, patients are often left with residual disability. Gaps in knowledge of the pathobiology of CSM have limited therapeutic advances to complement surgery. Although the histopathologic and pathophysiologic similarities between CSM and traumatic spinal cord injury have long been acknowledged, the unique pathomechanisms of CSM remain unexplored. Increased efforts to elucidate CSM pathobiology could lead to the discovery of novel therapeutic targets for human CSM and other spinal cord diseases. Here, the natural history of CSM, epidemiology, clinical presentation, and current methods of clinical management are reported, along with the current state of basic scientific research in the field.

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Section: Current Knowledge In Cervical Spondylotic Myelopathy Pathobimentioning

confidence: 99%

Cervical Spondylotic Myelopathy

Kalsi-Ryan

Karadimas

Fehlings³

2012

Neuroscientist

Self Cite

330

142

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“…Cervical radicular pain is pain perceived in the upper extremity, shooting or electric in quality, caused by irritation and/or injury of cervical spinal nerves (19,20). Cervical radicular pain may be caused either by disc herniation or compression due to other ailments in the cervical spine, or chemical irritation (18)(19)(20)(21)(22)(23)(24).…”

Section: Participantsmentioning

confidence: 99%

A Randomized, Double-Blind, Active Control Trial of Fluoroscopic Cervical Interlaminar Epidural Injections in Chronic Pain of Cervical Disc Herniation: Results of a 2-Year Follow-Up

Manchikanti

Ka²,

Pampati³

et al. 2013

Pain Phys

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Background: A recent evaluation of the state of U.S. health from 1990 to 2010 placed neck pain as the fourth condition leading to disability, with low back pain being the number one. Multiple treatment modalities have been described in managing neck and upper extremity pain secondary to cervical disc herniation after the failure of conservative management. The treatment modalities for chronic persistent pain of cervical disc herniation include surgery and epidural injections. The growth of interventional techniques in managing chronic spinal pain in recent years has been enormous. Evidence for the efficacy of cervical interlaminar epidural injections, however, continues to be debated, despite positive evidence derived from controlled randomized trials and systematic reviews. Study Design: A randomized, double-blind, active control trial. Setting: A private, specialty referral, interventional pain management practice in the United States. Objectives: To evaluate the effectiveness of epidural injections in managing chronic pain related to cervical disc herniation. Methods: Patients were randomly assigned to one of 2 groups of 60, with a total of 120 patients. Group I patients received cervical epidural injections with lidocaine 0.5% preservative-free, 5 mL, whereas Group II patients received 0.5% preservative-free lidocaine mixed with 1 mL or 6 mg of non-particulate betamethasone. Outcome Assessment: Multiple outcome measures included the numeric rating pain scale (NRS), the Neck Disability Index (NDI), employment status, opioid intake with assessment at 3, 6, 12, 18, and 24 months post treatment. Significant improvement was described as pain relief with a 50% improvement in functional status. Results: This evaluation showed significant improvement as 50% pain relief and improvement in functional status in 72% of the patients at 2 year follow-up in the local anesthetic group and 68% in those patients receiving local anesthetic and steroid. In the successful group of participants however, significant improvement was seen in 77% in Group I and 80% in Group II. Overall, the average number of procedures was 5 to 6 in both groups per 2 years. The average total relief for 2 years was 75.9 ± 29.9 weeks in Group I and 72.7 ± 31.1 in Group II, the successful group of participants. Taking into consideration all of the participants, the average total relief for 2 years was 69.6 ± 35 weeks in Group I and 62.1 ± 38.4 weeks in Group II. Limitations: The results of the study are limited by the lack of a placebo group. Conclusion: Cervical epidural injections with local anesthetic with or without steroids may offer significant benefit to patients suffering with chronic, persistent pain and disability related to cervical disc herniation. Key words: Chronic neck pain, cervical disc herniation, upper extremity pain, cervical epidural injections, epidural steroids, local anesthetics Trial Registration: NCT01071369

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“…Although the tumor necrosis factor-a, the mitogenactivated protein kinase pathways and the nuclear factor-j B [45] have been identified as potential apoptotic signaling pathways in CSM, there is also evidence that blocking the FasL signaling pathway results in decreased levels of cellular apoptosis and improved functional outcomes in CSM. It is obvious that only when identification of the extra and intracellular apoptotic pathways implicated in CSM is complete, we will be able to develop novel neuroprotective treatments for this disease.…”

Section: Apoptotic Cell Deathmentioning

confidence: 99%

Pathobiology of cervical spondylotic myelopathy

2014

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In this narrative review, we aim to outline what is currently known about the pathophysiology of cervical spondylotic myelopathy (CSM), the most common cause of spinal cord dysfunction. In particular, we note the unique factors that distinguish it from acute spinal cord injury. Despite its common occurrence, the reasons why some patients develop severe symptomatology while others have few or no symptoms despite radiographic evidence confirming similar degrees of compression is poorly understood. Neither is there a clear understanding of why certain patients have a stable clinical myelopathy and others present with only mild myelopathy. Moreover, the precise molecular mechanisms which contribute to the pathogenesis of the disease are incompletely understood. The current treatment method is decompression of the spinal cord but a lack of clinically relevant models of CSM have hindered the understanding of the full pathophysiology which would aid the development of new therapeutic avenues of investigation. Further elucidation of the role of ischemia, currently a source of debate, as well as the complex cascade of biomolecular events as a result of the unique pathophysiology in this disease will pave the way for further neuroprotective strategies to be developed to attenuate the physiological consequences of surgical decompression and augment its benefits.

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Immunohistochemical Profile of NF-κB/p50, NF-κB/p65, MMP-9, MMP-2, and u-PA in Experimental Cervical Spondylotic Myelopathy

Abstract: There is a strong correlation between the immunoexpression of NF-κB/p50, NF-κB/p65, MMP-2, MMP-9, u-PA, and CSM.

Cited by 38 publications

References 47 publications

Cervical Spondylotic Myelopathy

Cervical Spondylotic Myelopathy

A Randomized, Double-Blind, Active Control Trial of Fluoroscopic Cervical Interlaminar Epidural Injections in Chronic Pain of Cervical Disc Herniation: Results of a 2-Year Follow-Up

Pathobiology of cervical spondylotic myelopathy

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