Animal models of spinal cord injury: a systematic review

Sharif-Alhoseini, Mahdi; Khormali, Moein; Rezaei, Mojtaba; Safdarian, Mahdi; Hajighadery, Abdolkarim; Khalatbari, Mohammad; Meknatkhah, Sogol; Rezvan, Motahareh; Chalangari, M; Derakhshan, Pegah; Rahimi-Movaghar, Vafa

doi:10.1038/sc.2016.187

Cited by 206 publications

(174 citation statements)

References 54 publications

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“…For example, after spinal cord transection, mammals exhibit continual sublesional paralysis due to the complete lack of descending spinal circuitry (Baldwin, Haddad, Pandorf, Roy, & Edgerton, 2013), which produces extensive soleus atrophy and a gradual slow-tofast fiber transition that is characterized by fewer oxidative fibers and higher proportion of glycolytic fibers (Biering-Sorensen et al, 2009), and severe sublesional bone loss (Lin et al, 2018). However, spinal transection eliminates CNS input to the motor unit and to bone and does not reproduce the injury mechanism that occurs most frequently in persons with SCI, suggesting that pathophysiologic differences exist between the transection model and most humans with SCI (Sharif-Alhoseini et al, 2017). Alternatively, the rodent moderate contusion SCI model mimics the injury mechanism and pathophysiology occurring in persons with incomplete SCI.…”

Section: Introductionmentioning

confidence: 99%

Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury

Yarrow

Kok

Phillips

et al. 2019

J of Neuroscience Research

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Loading and testosterone may influence musculoskeletal recovery after spinal cord injury (SCI). Our objectives were to determine (a) the acute effects of bodyweight‐supported treadmill training (TM) on hindlimb cancellous bone microstructure and muscle mass in adult rats after severe contusion SCI and (b) whether longer‐term TM with adjuvant testosterone enanthate (TE) delivers musculoskeletal benefit. In Study 1, TM (40 min/day, 5 days/week, beginning 1 week postsurgery) did not prevent SCI‐induced hindlimb cancellous bone loss after 3 weeks. In Study 2, TM did not attenuate SCI‐induced plantar flexor muscles atrophy nor improve locomotor recovery after 4 weeks. In our main study, SCI produced extensive distal femur and proximal tibia cancellous bone deficits, a deleterious slow‐to‐fast fiber‐type transition in soleus, lower muscle fiber cross‐sectional area (fCSA), impaired muscle force production, and levator ani/bulbocavernosus (LABC) muscle atrophy after 8 weeks. TE alone (7.0 mg/week) suppressed bone resorption, attenuated cancellous bone loss, constrained the soleus fiber‐type transition, and prevented LABC atrophy. In comparison, TE+TM concomitantly suppressed bone resorption and stimulated bone formation after SCI, produced near‐complete cancellous bone preservation, prevented the soleus fiber‐type transition, attenuated soleus fCSA atrophy, maintained soleus force production, and increased LABC mass. 75% of SCI+TE+TM animals recovered voluntary over‐ground hindlimb stepping, while no SCI and only 20% of SCI+TE animals regained stepping ability. Positive associations between testosterone and locomotor function suggest that TE influenced locomotor recovery. In conclusion, short‐term TM alone did not improve bone, muscle, or locomotor recovery in adult rats after severe SCI, while longer‐term TE+TM provided more comprehensive musculoskeletal benefit than TE alone.

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Section: Introductionmentioning

confidence: 99%

Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury

Yarrow

Kok

Phillips

et al. 2019

J of Neuroscience Research

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“…This contusion produces a large central lesion that spares few axons in the rat (Anderson et al, 2009). We chose this model because it closely approximates the pathology of SCI in humans (Anderson et al, 2005; Sharif-Alhoseini et al, 2017) and it represents a highly demanding standard that must be achieved in order to move forward with a therapy. To facilitate the actions of the CST on damaged spinal motor circuits after SCI we used cathodal trans-spinal direct current stimulation (tsDCS).…”

Section: Introductionmentioning

confidence: 99%

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury

Zareen

Shinozaki

Ryan

et al. 2017

Experimental Neurology

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Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30 min daily for 10 days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury + stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury.

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“…The results from the present study illustrate how complicated the pathophysiology of the neurogenic LUT after SCI can be. We employed a well‐characterised animal model for SCI, which is common to the human condition after an accident and also leads to a range of locomotor and micturition impairments related to the contusion intensity . Our present findings show that after either semi‐acute (2 weeks) or semi‐chronic (4 weeks) post‐SCI periods, significant changes to the electrophysiological function of the LUT can be evidenced and evaluated.…”

Section: Discussionmentioning

confidence: 63%

Modulatory effects of intravesical P2X2/3 purinergic receptor inhibition on lower urinary tract electromyographic properties and voiding function of female rats with moderate or severe spinal cord injury

et al. 2018

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Objectives To evaluate the role that intravesical P2X2/3 purinergic receptors (P2X2/3Rs) play in early and advanced neurogenic lower urinary tract (LUT) dysfunction after contusion spinal cord injury (SCI) in female rats. Materials and Methods Female Sprague‐Dawley rats received a thoracic Th8/Th9 spinal cord contusion with either force of 100 kDy (cN); moderate) or 150 kDy (cN; severe); Sham rats had no injury. Evaluations on urethane‐anesthetised rats were conducted at either 2 or 4 weeks after SCI. LUT electrical signals and changes in bladder pressure were simultaneously recorded using cystometry and a set of custom‐made flexible microelectrodes, before and after intravesical application of the P2X2/3R antagonist AF‐353 (10 μM), to determine the contribution of P2X2/3R‐mediated LUT modulation. Results Severe SCI significantly increased bladder contraction frequency, and reduced both bladder pressure amplitude and intraluminal‐pressure high‐frequency oscillations (IPHFO). Intravesical P2X2/3R inhibition did not modify bladder pressure or IPHFO in the Sham and moderate‐SCI rats, although did increase the intercontractile interval (ICI). At 2 weeks after SCI, the Sham and moderate‐SCI rats had significant LUT electromyographic activity during voiding, with a noticeable reduction in LUT electrical signals seen at 4 weeks after SCI. Intravesical inhibition of P2X2/3R increased the ICI in the Sham and moderate‐SCI rats at both time‐points, but had no effect on rats with severe SCI. The external urethral sphincter (EUS) showed strong and P2X2/3R‐independent electrical signals in the Sham and moderate‐SCI rats in the early SCI stage. At 4 weeks after SCI, the responsiveness of the EUS was significantly attenuated, independently of SCI intensity. Conclusions This study shows that electrophysiological properties of the LUT are progressively impaired depending on SCI intensity and that intravesical P2X2/3R inhibition can attenuate electrical activity in the neurogenic LUT at early, but not at semi‐chronic SCI. This translational study should be useful for planning clinical evaluations.

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Animal models of spinal cord injury: a systematic review

Cited by 206 publications

References 54 publications

Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury

Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury

Modulatory effects of intravesical P2X2/3 purinergic receptor inhibition on lower urinary tract electromyographic properties and voiding function of female rats with moderate or severe spinal cord injury

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