White Matter Injury in Spinal Cord Ischemia

Kanellopoulos, Georgios K.; Xu, Xiao Ming; Hsu, Chung Y.; Lü, Xiaobin; Sundt, Thoralf M.; Kouchoukos, Nicholas T.

doi:10.1161/01.str.31.8.1945

Cited by 88 publications

(15 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The severity of white matter damage, assessed by MBP immunostaining, in a rat model of perinatal hypoxia-ischemia was reduced by systemic administration of NBQX (Follett et al, 2000). This agent also attenuated the extent of axonal damage, assessed by neurofilament immunostaining, and improved locomotor function in a rat model of spinal cord ischemia (Kanellopoulos et al, 2000). After traumatic injury to the spinal cord of rats, NBQX not only improved the survival of oligodendrocytes but also reduced axonal injury and attenuated impairment of locomotor function (Rosenberg et al, 1999;Wrathall et al, 1994Wrathall et al, , 1996Wrathall et al, , 1997.…”

Section: Glutamate Receptor Antagonistsmentioning

confidence: 92%

Oligodendrocytes and Ischemic Brain Injury

Dewar

Underhill

Goldberg

2003

J Cereb Blood Flow Metab

260

129

View full text Add to dashboard Cite

Summary:Oligodendrocytes, myelin-forming glial cells of the central nervous system, are vulnerable to damage in a variety of neurologic diseases. Much is known of primary myelin injury, which occurs in settings of genetic dysmyelination or demyelinating disease. There is growing awareness that oligodendrocytes are also targets of injury in acute ischemia. Recognition of oligodendrocyte damage in animal models of ischemia requires attention to their distinct histologic features or use of specific immunocytochemical markers. Like neurons, oligodendrocytes are highly sensitive to injury by oxidative stress, excitatory amino acids, trophic factor deprivation, and activation of apoptotic pathways. Understanding mechanisms of oligodendrocyte death may suggest new therapeutic strategies to preserve or restore white matter function and structure after ischemic insults.

show abstract

Section: Glutamate Receptor Antagonistsmentioning

confidence: 92%

Oligodendrocytes and Ischemic Brain Injury

Dewar

Underhill

Goldberg

2003

J Cereb Blood Flow Metab

260

129

View full text Add to dashboard Cite

show abstract

“…23 It has been shown that both gray and white matter were damaged after spinal cord ischemia in rats, and the severity of white matter injury was correlated with the degree of gray matter injury. 24,25 Kannellopoulos et al 26 demonstrated widespread and prominent vacuolation in white matter 2 days after the experimental spinal cord ischemia. The mechanism of injury induced by reoxygenation in axons has been proposed to be the failure of respiration due to severe mitochondrial Ca 2 þ overload.…”

Section: Discussionmentioning

confidence: 99%

Assessment of in vivo spinal cord conduction velocity in rats in an experimental model of ischemic spinal cord injury

et al. 2013

View full text Add to dashboard Cite

Study design: Experimental laboratory investigation of spinal cord conductivity alterations in a rat model of ischemic spinal cord injury (SCI). Objective: To observe the epidural spinal cord stimulation-induced electromyography responses, and to investigate the possible alterations of spinal cord conduction velocity (SCCV) and compound muscle action potentials (CMAPs) after ischemic SCI in rats. Settings: Adnan Menderes University, Institute of Health Science, Aydin, Turkey. Methods: SCI was induced by transient occlusion of the abdominal aorta in male Sprague-Dawley rats. Spinal cord histopathology was examined to determine neuronal damage and Tarlov scale was used to grade locomotor functions. Epidural electrical stimulation of spinal cord was performed by monopolar needle electrodes sequentially at L1-L2 and L5-L6 levels, and CMAPs were recorded from the left gastrocnemius muscle by surface electrodes. Amplitudes and durations of CMAPs were evaluated and SCCVs were calculated by analyzing the latency difference of CMAPs. Results: Ischemia-induced SCI resulted in significant reduction of Tarlov scores and a significant decline in number of viable neurons. Similarly, a significant decrement was observed in SCCV following spinal cord ischemia. Conclusion: This study demonstrated that measurement of SCCV via epidural electrical stimulation is possible and displays a significant decline after spinal cord ischemia in rats. We suggest that this method can be beneficial to quantify neuronal damage after experimental ischemic SCI. Rats are commonly used in experimental studies owing to the firm analogy of spinal cord anatomy between these animals and humans. 2 Motor functions after SCI are generally evaluated by locomotor scales such as Basso Beattie and Bresnahan (BBB) and Tarlov scales. These qualitative assessment methods are performed by visual inspection and scoring of hind limb activity, and mainly determine fine locomotor skills. 3 However, there are difficulties in objective determination of neurological status following SCI in rats, which drive the attempts for developing more quantitative methods. 4,5 Various alternative methods have been developed for quantitative determination of motor deficits after SCI in rodents, which involve employment of video assistance such as single-frame motion analysis, 5 automated quantitative gait analysis 4 or robotic devices. 6

show abstract

“…OLG death in these disorders results, in part, from excitotoxicity involving AMPA receptor (McDonald et al, 1998;Smith et al, 2000;Miller and Mi, 2007). AMPA receptor antagonism is effective in salvaging white matter after traumatic or ischemic SCI (Wrathall et al, 1994;Kanellopoulos et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid Protection of Oligodendrocytes against Excitotoxin Involving Hypoxia-Inducible Factor-1 in a Cell-Type-Specific Manner

Sun¹,

Wang²,

Hsu³

et al. 2010

Journal of Neuroscience

View full text Add to dashboard Cite

Glucocorticoids are commonly used in treating diseases with white matter lesions, including demyelinating diseases and spinal cord injury (SCI). However, glucocorticoids are ineffective in gray matter injuries, such as head injury and stroke. The differential glucocorticoid effects in white and gray matter injuries are unclear. We report here a novel mechanism of methylprednisolone (MP), a synthetic glucocorticoid widely used for treating multiple sclerosis and SCI, in protecting oligodendrocytes (OLGs) against AMPA-induced excitotoxicity, which has been implicated in the white matter injuries and diseases. The cytoprotective action of MP in OLGs is causally related to its upregulation of a neuroprotective cytokine erythropoietin (Epo). MP transactivation of Epo expression involves dual transcription factors: glucocorticoid receptor (GR) and hypoxia-inducible factor-1␣ (HIF-1␣). Coimmunoprecipitation, chromatin immunoprecipitation analysis, yeast two-hybrid analysis, and structure modeling of three-dimensional protein-protein interactions confirm that MP induces interaction between GR DNA binding domain and HIF-1␣ PAS domain, with subsequent recruitment of HIF-1␤ to transactivate Epo expression in OLGs. In contrast, MP activates GR but does not induce GR-HIF-1␣ interaction, HIF-1␣ binding to Epo enhancer/ promoter, or Epo expression in cultured cortical neurons. The OLG-specific GR-HIF-1␣ transactivation of Epo provides novel insights into the development of more effective therapies for diseases affecting the white matter.

show abstract

White Matter Injury in Spinal Cord Ischemia

Cited by 88 publications

References 51 publications

Oligodendrocytes and Ischemic Brain Injury

Oligodendrocytes and Ischemic Brain Injury

Assessment of in vivo spinal cord conduction velocity in rats in an experimental model of ischemic spinal cord injury

Glucocorticoid Protection of Oligodendrocytes against Excitotoxin Involving Hypoxia-Inducible Factor-1 in a Cell-Type-Specific Manner

Contact Info

Product

Resources

About