Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion

Pan, Jonathan Z.; Ni, Li; Sodhi, Ajeet; Aguanno, Ann; Young, Wise; Hart, Ronald P.

doi:10.1002/jnr.10215

Cited by 135 publications

(105 citation statements)

References 37 publications

(47 reference statements)

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“…[28][29][30][31] Several mouse SCI models, such as weight-drop, contusion and compression have been well established and applied to study SCI-mediated neuropathophysiological functions. 1,32 The reason that we adopted the compression approach to induce spinal cord injury is based on its reproducibility and simplicity. 13 As shown in Figure 1, the morphological, histological and pathological alterations in SCI compared to that of surgical control provided in this study reproduced and validated previous observations in the compression and other SCI models.…”

Section: Discussionmentioning

confidence: 99%

Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury

et al. 2004

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Study design: Experimental laboratory investigation of the role and pathways of reactive oxygen species (ROS)-mediated motor neuron cell death in a mouse model of compression spinal cord injury. Objectives: To analyze ROS-mediated oxidative stress propagation and signal transduction leading to motor neuron apoptosis induced by compression spinal cord injury. Setting: University of Louisville Health Science Center. Methods: Adult C57BL/6J mice and transgenic mice overexpressing SOD1 were severely lesioned at the lumbar region by compression spinal cord injury approach. Fluorescent oxidation, oxidative response gene expression and oxidative stress damage markers were used to assay spinal cord injury-mediated ROS generation and oxidative stress propagation. Biochemical and immunohistochemical analyses were applied to define the ROS-mediated motor neuron apoptosis resulted from compression spinal cord injury. Results: ROS production was shown to be elevated in the lesioned spinal cord as detected by fluorescent oxidation assays. The early oxidative stress response markers, NF-kB transcriptional activation and c-Fos gene expression, were significantly increased after spinal cord injury. Lipid peroxidation and nucleic acid oxidation were also elevated in the lesioned spinal cord and motor neurons. Cytochrome c release, caspase-3 activation and apoptotic cell death were increased in the spinal cord motor neuron cells after spinal cord injury. On the other hand, transgenic mice overexpressing SOD1 showed lower levels of steady-state ROS production and reduction of motor neuron apoptosis compared to that of control mice after spinal cord injury. Conclusion: These data together provide direct evidence to demonstrate that the increased production of ROS is an early and likely causal event that contributes to the spinal cord motor neuron death following spinal cord injury. Thus, antioxidants/antioxidant enzyme intervention combined with other therapy may provide an effective approach to alleviate spinal cord injuryinduced motor neuron damage and motor dysfunction.

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Section: Discussionmentioning

confidence: 99%

Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury

et al. 2004

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“…This study group recommended standardization of conditions that included the use of Long Evans rats that are 77±1 days old, a pentobarbital dosage of 45 and 60 mg kg À1 for females and males, respectively, and infliction of injury 60 ± 1 min after induction of anesthesia. 8 Because of practical considerations, however, strict adherence to these recommendations is challenging.…”

Section: New York University (Nyu)/multicenter Animal Spinal Cord Injmentioning

confidence: 99%

“…4,8 Although most of the literature involves thoracic-level injuries, the MASCIS impactor has been used to generate injury in the cervical spine in a rat model. 5 Weight-drop methods in the pig and dog that rely on similar principles as the MASCIS devices have recently been described.…”

Section: New York University (Nyu)/multicenter Animal Spinal Cord Injmentioning

confidence: 99%

Spinal cord injury models: a review

et al. 2014

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Background: Animal spinal cord injury (SCI) models have proved invaluable in better understanding the mechanisms involved in traumatic SCI and evaluating the effectiveness of experimental therapeutic interventions. Over the past 25 years, substantial gains have been made in developing consistent, reproducible and reliable animal SCI models. Study design: Review. Objective: The objective of this review was to consolidate current knowledge on SCI models and introduce newer paradigms that are currently being developed. Results: SCI models are categorized based on the mechanism of injury into contusion, compression, distraction, dislocation, transection or chemical models. Contusion devices inflict a transient, acute injury to the spinal cord using a weight-drop technique, electromagnetic impactor or air pressure. Compression devices compress the cord at specific force and duration to cause SCI. Distraction SCI devices inflict graded injury by controlled stretching of the cord. Mechanical displacement of the vertebrae is utilized to produce dislocation-type SCI. Surgical transection of the cord, partial or complete, is particularly useful in regenerative medicine. Finally, chemically induced SCI replicates select components of the secondary injury cascade. Although rodents remain the most commonly used species and are best suited for preliminary SCI studies, large animal and nonhuman primate experiments better approximate human SCI. Conclusion: All SCI models aim to replicate SCI in humans as closely as possible. Given the recent improvements in commonly used models and development of newer paradigms, much progress is anticipated in the coming years. Spinal Cord (2014) 52, 588-595; doi:10.1038/sc.2014.91; published online 10 June 2014 INTRODUCTIONSpinal cord injury (SCI) models have proved indispensible not only for investigating the efficacy of therapeutic interventions but also for better understanding the molecular pathways involved. SCI models have evolved significantly over the past century since Allen developed the first weight-drop contusion model in 1911. 1 SCI models aim to recreate features of human SCI as closely as possible. These models vary in terms of the animal utilized, site of injury infliction and injury mechanism.Rats are used most commonly in preliminary studies as they are relatively inexpensive, readily available and have demonstrated similar functional, electrophysiological, and morphological outcomes to humans following SCI. 2 Mice are particularly useful for genetic studies. 3 Nonhuman primate SCI models-including marmosets, macaques and squirrel monkeys-better approximate human SCI than rodent models, and they accommodate assessment of multiple recovery variables and rehabilitative therapy. 4 New world primates like marmosets confer advantages over old world primates as they are smaller, easier to handle, have a higher breeding efficiency and can be bred in experimental colonies. SCI models that incorporate large animals-such as pigs or dogs-can also be used when it is important for furth...

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“…99 Following experimental SCI, transcripts of both the proinflammatory cytokines, TNF-a, IL-1b, and IL-6 and the chemokines, MIP-1a and MIP-1b, are upregulated within the first hour postinjury. 100 However, the expression of TNF-a is nearly completely downregulated by 24 h. 2,5,57,101 Therefore, CNS cells, and not the invading non-CNS resident cells, seem to be the source of the transcripts. In juvenile rats, an age-related 'window of susceptibility' to the inflammatory stimulus on leucocytes and BBB permeability secondary to an intracerebral IL-1b injection has been demonstrated.…”

Section: Regulation Of Cns Inflammationmentioning

confidence: 99%