scholarly journals Quantification of surviving neurons after contusion, dislocation, and distraction spinal cord injuries using automated methods

2019 ◽  
Vol 13 ◽  
pp. 117906951986961
Author(s):  
Jingchao Wang ◽  
Meiyan Zhang ◽  
Yue Guo ◽  
Hai Hu ◽  
Kinon Chen

This study proposes and validates an automated method for counting neurons in spinal cord injury (SCI) and then uses it to examine and compare the surviving cells in common types of SCI mechanisms. Moderate contusion, dislocation, and distraction SCIs were surgically induced in Sprague Dawley male rats (n = 6 for each type of injury). Their spinal cords were harvested 8 weeks post injury with 5 normal weight-matched rats. The spinal cords were cut, stained with anti-NeuN antibody and fluorescent Nissl, and imaged in the dorsal and ventral horns at various distances to the epicenter. Neurons in the images were automatically counted using an algorithm that was designed to filter non-soma-like objects based on morphological characteristics (size, solidity, circular pattern) and check the remaining objects for the double-stained nucleus/cell body features (brightness variation, brightness distribution, color). To validate the automated method, some of the images were randomly selected for manual counting. The number of surviving cells that were automatically measured by the algorithm was found to be correlated with the values that were manually measured by 2 observers ( P < .001) with similar differences ( P > .05). Neurons in the dorsal and ventral horns were reduced after the SCIs ( P < .05). Dislocation and distraction, respectively, caused the most severe damage to the ventral horn neurons especially near the epicenter and the most extensive and uniform damage to the dorsal horn neurons ( P < .05). Our method was proved to be reliable, which is suitable for studying different types of SCI.

2019 ◽  
Vol 13 ◽  
pp. 117906951986961 ◽  
Author(s):  
Yue Guo ◽  
Hai Hu ◽  
Jingchao Wang ◽  
Meiyan Zhang ◽  
Kinon Chen

This study examines and compares the walking function in contusion and distraction spinal cord injury (SCI) mechanisms. Moderate contusion and distraction SCIs were surgically induced between C5 and C6 in Sprague-Dawley male rats. The CatWalk system was used to perform gait analysis of walkway walking. The ladder rung walking test was used to quantify skilled locomotor movements of ladder rung walking. It was found that the inter-paw coordination, paw support, front paw kinematics, hind paw kinematics, and skilled movements were significantly different before and after contusion and distraction. Step sequence duration, diagonal support, forelimb intensity, forelimb duty cycle, forelimb paw angle, and forelimb swing speed were more greatly affected in distraction than in contusion at 2 weeks post-injury, whereas hindlimb stand was more greatly affected in contusion than in distraction at 8 weeks post-injury. After 8 weeks post-injury, diagonal coupling—variation, girdle coupling—variation, ipsilateral coupling—mean, forelimb maximum contact at, forelimb intensity, forelimb paw angle, and number of forelimb misplacements recovered to normal in contusion but not in distraction, whereas step sequence duration, ipsilateral coupling—variation, forelimb stand, forelimb duty cycle, hindlimb swing duration, hindlimb swing speed, and number of forelimb slips recovered to normal in distraction but not in contusion. Some of the behavioral outcomes, but not the others, were linearly correlated with the histological outcomes. In conclusion, walking deficits and recovery can be affected by the type of common traumatic SCI.


2019 ◽  
Vol 6 (3) ◽  
pp. 83-91
Author(s):  
Mohaddeseh Hedayatzadeh ◽  
Hamid Reza Kobravi ◽  
Maryam Tehranipour

Background: Spinal cord injury is one of the diseases that, no specific treatment has yet found despite the variety of works that have done in this field. Different approaches to treat such injuries have investigated today. One of them is invasive intra-spinal interventions such as electrical stimulation. Therefore, in this study, the effect of the protocol for intra-spinal variable and fixed electrical stimulation has been investigated in order to recover from spinal cord injury. Methods: In the study, 18 Wistar male rats randomly divided into Three groups, including intraspinal electrical stimulation (IES), IES with variable pattern of stimulation (VP IES) and a sham group. Animals initially subjected to induced spinal cord injury. After one week, the animal movement was recorded on the treadmill during practice using a camera and angles of the ankle joint were measured using the Tracker software. Then, the obtained data were analyzed by nonlinear evaluations in the phase space. Results: The motion analyses and kinematic analyses were carried out on all groups. According to the achieved results, the gait dynamics of the VP IES group has the most conformity to the gait dynamics of the healthy group. Also, the best quality of the balance preservation observed in the VP IES group. Conclusion: It can be concluded that the IES with variable pattern of stimulation along with exercise therapy has significant gait restorative effects and increases the range of motion in rats with induced spinal cord injury.


1996 ◽  
Vol 5 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Gregory Murphy ◽  
Douglas Brown ◽  
Peter Foreman ◽  
Amanda Young ◽  
James Athanasou

The educational and vocational achievements of a sample of Australians with spinal cord injuries are described in this study. Of the 180 working-age people surveyed, 36% were holding full-time or part-time employment at the time of the survey and one-third had gone on to obtain further qualifications post-injury. The most frequent methods of finding a job post-injury were informal rather than formal, with only 5% of jobs gained through advertisements or employment services. Of those who gained work, 49% did so within 12 months of discharge, but another 14% obtained their job more than five years after initial hospital discharge. The results indicate that there is considerable scope for employment and education achievements following spinal cord injury.


Author(s):  
Tzu-Ting Chiu ◽  
Kun-Ze Lee

Cervical spinal cord injury typically results in respiratory impairments. Clinical and animal studies have demonstrated that respiratory function can spontaneously and partially recover over time after injury. However, it remains unclear whether respiratory recovery is associated with alterations in metabolism. The present study was designed to comprehensively examine ventilation and metabolism in a rat model of spinal cord injury. Adult male rats received sham (i.e., laminectomy) or unilateral mid-cervical contusion injury (height of impact rod: 6.25 or 12.5 mm). Breathing patterns and whole-body metabolism (O2 consumption and CO2 production) were measured using a whole-body plethysmography system conjugated with flow controllers and gas analyzer at the acute (1 day post-injury), subchronic (2 weeks post-injury), and chronic (8 weeks post-injury) injury stages. The results demonstrated that mid-cervical contusion caused a significant reduction in the tidal volume. Although the tidal volume of contused animals can gradually recover, it remains lower than that of uninjured animals at the chronic injury stage. While O2 consumption and CO2 production were similar between uninjured and contused animals at the acute injury stage, these two metabolic parameters were significantly reduced in contused animals at the subchronic to chronic injury stages. Additionally, the relationships between ventilation, metabolism, and body temperature were altered by cervical spinal cord injury. These results suggest that cervical spinal cord injury causes a complicated reconfiguration of ventilation and metabolism that may enable injured animals to maintain a suitable homeostasis for adapting to the pathophysiological consequences of injury.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lan Huong Nguyen ◽  
Mingyong Gao ◽  
Junquan Lin ◽  
Wutian Wu ◽  
Jun Wang ◽  
...  

Abstract Spinal cord injuries (SCI) often lead to persistent neurological dysfunction due to failure in axon regeneration. Unfortunately, currently established treatments, such as direct drug administration, do not effectively treat SCI due to rapid drug clearance from our bodies. Here, we introduce a three-dimensional aligned nanofibers-hydrogel scaffold as a bio-functionalized platform to provide sustained non-viral delivery of proteins and nucleic acid therapeutics (small non-coding RNAs), along with synergistic contact guidance for nerve injury treatment. A hemi-incision model at cervical level 5 in the rat spinal cord was chosen to evaluate the efficacy of this scaffold design. Specifically, aligned axon regeneration was observed as early as one week post-injury. In addition, no excessive inflammatory response and scar tissue formation was triggered. Taken together, our results demonstrate the potential of our scaffold for neural tissue engineering applications.


Dose-Response ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 155932582199813
Author(s):  
Rakib Uddin Ahmed ◽  
V. Reggie Edgerton ◽  
Shuai Li ◽  
Yong-Ping Zheng ◽  
Monzurul Alam

Buspirone, widely used as a neuropsychiatric drug, has also shown potentials for motor function recovery of injured spinal cord. However, the optimum dosages of such treatment remain unclear. In this study, we investigated the dose-response of Buspirone treatment on reaching and grasping function in cervical cord injured rats. Seventeen adult Sprague-Dawley rats were trained to reach and grasp sugar pellets before a C4 bilateral dorsal column crush injury. After 1 week post-injury, the rats were divided into 3 groups to receive 1 of 3 different dosages of Buspirone (i.p., 1 dose/day: 1.5, n = 5; 2.5, n = 6 and 3.5 mg/kg b.w., n = 6). Forelimb reaching and grip strength test were recorded once per week, within 1 hour of Buspirone administration for 11 weeks post-injury. Different dose groups began to exhibit differences in reaching scores from 4 weeks post-injury. From 4-11 weeks post-injury, the reaching scores were highest in the lowest-dose group rats compared to the other 2 dose groups rats. Average grip strength was also found higher in the lowest-dose rats. Our results demonstrate a significant dose-dependence of Buspirone on the recovery of forelimb motor functions after cervical cord injury with the best performance occurring at the lowest dose tested.


2021 ◽  
Vol 22 (20) ◽  
pp. 11012
Author(s):  
Yiyoung Kim ◽  
Eun Ji Roh ◽  
Hari Prasad Joshi ◽  
Hae Eun Shin ◽  
Hyemin Choi ◽  
...  

In research on various central nervous system injuries, bazedoxifene acetate (BZA) has shown two main effects: neuroprotection by suppressing the inflammatory response and remyelination by enhancing oligodendrocyte precursor cell differentiation and oligodendrocyte proliferation. We examined the effects of BZA in a rat spinal cord injury (SCI) model. Anti-inflammatory and anti-apoptotic effects were investigated in RAW 264.7 cells, and blood-spinal cord barrier (BSCB) permeability and angiogenesis were evaluated in a human brain endothelial cell line (hCMEC/D3). In vivo experiments were carried out on female Sprague Dawley rats subjected to moderate static compression SCI. The rats were intraperitoneally injected with either vehicle or BZA (1mg/kg pre-SCI and 3mg/kg for 7 days post-SCI) daily. BZA decreased the lipopolysaccharide-induced production of proinflammatory cytokines and nitric oxide in RAW 264.7 cells and preserved BSCB disruption in hCMEC/D3 cells. In the rats, BZA reduced caspase-3 activity at 1 day post-injury (dpi) and suppressed phosphorylation of MAPK (p38 and ERK) at dpi 2, hence reducing the expression of IL-6, a proinflammatory cytokine. BZA also led to remyelination at dpi 20. BZA contributed to improvements in locomotor recovery after compressive SCI. This evidence suggests that BZA may have therapeutic potential to promote neuroprotection, remyelination, and functional outcomes following SCI.


2019 ◽  
Vol 11 ◽  
pp. 117957351984162 ◽  
Author(s):  
Camila Quel de Oliveira ◽  
James W Middleton ◽  
Kathryn Refshauge ◽  
Glen M Davis

Introduction: Activity-based therapy (ABT) aims to activate the neuromuscular system below the level of the spinal cord lesion and promote recovery of motor tasks through spinal reorganisation, motor learning and changes to muscles and sensory system. We investigated the effects of a multimodal ABT program on mobility, independence and sitting balance in individuals with spinal cord injury (SCI). Methods: Retrospective clinical data from 91 adults who independently enrolled in four community-based ABT centres in Australia were analysed. The multimodal ABT program was delivered for 3 to 12 months, one to four times per week. Assessments were undertaken every 3 months and included the Modified Rivermead Mobility Index (MRMI), Spinal Cord Independence Measure (SCIM) and seated reach distance (SRD). A linear mixed model analysis was used to determine time-based and other predictors of change. Results: There was a significant improvement after 12 months for all outcome measures, with a mean change score of 4 points in the SCIM (95% confidence interval [CI]: 2.7-5.3, d = 0.19), 2 points in the MRMI (95% CI: 1-2.3, d = 0.19) and 0.2 in the SRD (95% CI: 0.1-2.2, d = 0.52). Greater improvements occurred in the first 3 months of intervention. There were no interaction effects between time and the neurological level of injury, American Spinal Injury Association Impairment Scale classification, or duration post-injury for most outcomes. Conclusions: A community-based ABT exercise program for people with SCI can lead to small improvements in mobility, independence and balance in sitting, with greater improvements occurring early during intervention.


2010 ◽  
Vol 298 (5) ◽  
pp. R1358-R1365 ◽  
Author(s):  
Heidi L. Lujan ◽  
Gurunanthan Palani ◽  
Jean D. Peduzzi ◽  
Stephen E. DiCarlo

Individuals with spinal cord injuries above thoracic level 6 (T6) experience episodic bouts of life-threatening hypertension as part of a condition termed autonomic dysreflexia. The paroxysmal hypertension can be caused by a painful stimulus below the level of the injury. Targeted ablation of mesenteric projecting sympathetic neurons may reduce the severity of autonomic dysreflexia by reducing sympathetic activity. Therefore, cholera toxin B subunit (CTB) conjugated to saporin (SAP; a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected into the celiac ganglion to test the hypothesis that targeted ablation of mesenteric projecting sympathetic neurons reduces the pressor response to pain in conscious, spinal cord-transected rats. Nine Sprague-Dawley male rats underwent a spinal cord transection between thoracic vertebrae 4 and 5. Following recovery (5 wk), all rats were instrumented with a radio telemetry device for recording arterial pressure and bilateral catheters in the gluteus maximus muscles for the infusion of hypertonic saline (hNa+Cl−). Subsequently, the hemodynamic responses to intramuscular injection of hNa+Cl− (100 μl and 250 μl, in random order) were determined. Following the experiments in the no celiac ganglia injected condition (NGI), rats received injections of CTB-SAP ( n = 5) or CTB ( n = 3) into the celiac ganglia. CTB-SAP rats, compared with NGI and CTB rats, had reduced pressor responses to hNa+Cl−. Furthermore, the number of stained neurons in the celiac ganglia and spinal cord (segments T6–T12), was reduced in CTB-SAP rats. Thus, CTB-SAP retrogradely transported from the celiac ganglia is effective at ablating mesenteric projecting sympathetic neurons and reducing the pressor response to pain in spinal cord-transected rats.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xuankang Wang ◽  
Xin Li ◽  
Xiaoshuang Zuo ◽  
Zhuowen Liang ◽  
Tan Ding ◽  
...  

Abstract Background Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. Methods Male Sprague–Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. Results PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. Conclusion Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.


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