Olfactory bulb transplantation in complete spinal cord injury: axonal regeneration and locomotor recovery

OBJECTIVES: To determine whether the intervention in rats is effective in terms of spinal cord regeneration and locomotor recovery, in order to obtain sufficient evidence to apply the therapy in humans. METHODS: a randomized, controlled, experimental, prospective, randomized trial was conducted, with a sample of 15 adult female Sprague-Dawley rats weighing 250 gr. They were divided into three equal groups, and trained for 2 weeks based on Pavlov's classical conditioning method, to strengthen the muscles of the 4 legs, stimulate the rats mentally, and keep them healthy for the surgery. RESULTS: It was observed that implantation of these cells into the site of injury may be beneficial to the process of spinal cord regeneration after spinal trauma, to mediate secretion of neurotrophic and neuroprotective chemokines, and that the OECs have the ability to bridge the repair site and decrease the formation of gliosis, creating a favorable environment for axonal regeneration. CONCLUSION: It is emphasized that the olfactory ensheathing glial cells possess unique regenerative properties; however, it was not until recently that the activity of promoting central nervous system regeneration was recognized.

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α1D-Adrenoceptor blockade increases voiding efficiency by improving external urethral sphincter activity in rats with spinal cord injury

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00030.2016 ◽

2016 ◽

Vol 311 (5) ◽

pp. R971-R978 ◽

Cited By ~ 2

Author(s):

Hirokazu Ishida ◽

Hiroki Yamauchi ◽

Hideaki Ito ◽

Hironobu Akino ◽

Osamu Yokoyama

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Lower Urinary Tract Dysfunction ◽

Urethral Sphincter ◽

Sprague Dawley ◽

External Urethral Sphincter ◽

Detrusor Sphincter Dyssynergia ◽

Sphincter Electromyography ◽

Sprague Dawley Rats ◽

Cord Injury

Ideal therapy for lower urinary tract dysfunction in patients with spinal cord injury (SCI) should decrease detrusor overactivity, thereby promoting urine storage at low intravesical pressure and promoting efficient voiding at low pressure by decreasing detrusor-sphincter dyssynergia. Here we investigated blockade of various α-adrenoceptors to determine the subtype that was principally responsible for improving the voiding dysfunction. The effects of the intravenous α-blocker naftopidil, the α-blocker BMY 7378, and the α-blocker silodosin were evaluated using cystometrography and external urethral sphincter-electromyography (EMG) in decerebrated, unanesthetized female Sprague-Dawley rats with chronic SCI following transection at Th8. Parameters measured included the voided volume, residual volume, voiding efficiency, and burst and silent periods on EMG. Compared with values in decerebrated non-SCI rats, EMG of decerebrated SCI rats revealed more prominent tonic activity, significantly shorter periods of bursting activity, and a reduced ratio of the silent to active period during bursting. Compared with the value before drug administration (control), the voiding efficiency was significantly increased by naftopidil (1 and 3 mg/kg) (<0.05 each), and the burst (<0.01 and <0.05, respectively) and silent periods (<0.01 each) on EMG were significantly lengthened. BMY 7378 (1 mg/kg) significantly increased voiding efficiency and lengthened the burst periods (<0.05 each). Silodosin did not affect any parameters. These results suggest that α-blockade reduces the urethral resistance associated with detrusor-sphincter dyssynergia, thus improving voiding efficiency in SCI rats.

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Taurine promotes axonal regeneration after a complete spinal cord injury in lampreys

IBRO Reports ◽

10.1016/j.ibror.2019.07.1584 ◽

2019 ◽

Vol 6 ◽

pp. S507-S508

Author(s):

Antón Barreiro-Iglesias ◽

Daniel Sobrido-Cameán ◽

Blanca Fernández-López ◽

Natividad Pereiro ◽

Anunciación Lafuente ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Axonal Regeneration ◽

Cord Injury ◽

Complete Spinal Cord Injury

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Limited functional recovery in rats with complete spinal cord injury after transplantation of whole-layer olfactory mucosa

Journal of Neurosurgery Spine ◽

10.3171/2009.9.spine09233 ◽

2010 ◽

Vol 12 (2) ◽

pp. 122-130 ◽

Cited By ~ 30

Author(s):

Masanori Aoki ◽

Haruhiko Kishima ◽

Kazuhiro Yoshimura ◽

Masahiro Ishihara ◽

Masaki Ueno ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Lamina Propria ◽

Motor Function ◽

Functional Recovery ◽

Olfactory Mucosa ◽

Respiratory Mucosa ◽

Locomotor Recovery ◽

Cord Injury ◽

Complete Spinal Cord Injury

Object The olfactory mucosa (OM) consists of 2 layers, the epithelium and the lamina propria. Attempts have been made to restore motor function in rat models of spinal cord injury (SCI) by transplanting olfactory ensheathing cells from the lamina propria, but there has been no attempt to transplant the OM in animal models. To investigate the potential of the OM to restore motor function, the authors developed a rat model of SCI and delayed transplantation of syngenic OM. Methods Two weeks after complete transection of the spinal cord at the T-10 level in Wistar rats, pieces of syngenic whole-layer OM were transplanted into the lesion. Rats that underwent respiratory mucosa transplantation were used as controls. The authors evaluated the locomotor activity according to the Basso-Beattie-Bresnahan scale for 8 weeks after transplantation. Obtained spinal cords were analyzed histologically. Results The OM transplantation rats showed significantly greater hindlimb locomotor recovery than the respiratory mucosa–transplanted rats. However, the recovery was limited according to the Basso-Beattie-Bresnahan scale. In the histological examination, the serotonergic raphespinal tract was regenerated. The pseudocyst cavity volume in the vicinity of the SCI lesion correlated negatively with the functional recovery. Conclusions Transplantation of whole-layer OM in rats contributes to functional recovery from SCI, but the effect is limited. In addition to OM transplantation, other means would be necessary for better outcomes in clinical situations.

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Paired Immunoglobulin-like Receptor B Knockout Does Not Enhance Axonal Regeneration or Locomotor Recovery after Spinal Cord Injury

Journal of Biological Chemistry ◽

10.1074/jbc.m110.163493 ◽

2010 ◽

Vol 286 (3) ◽

pp. 1876-1883 ◽

Cited By ~ 47

Author(s):

Yuka Nakamura ◽

Yuki Fujita ◽

Masaki Ueno ◽

Toshiyuki Takai ◽

Toshihide Yamashita

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Axonal Regeneration ◽

Locomotor Recovery ◽

Cord Injury

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Contralateral Axon Sprouting but Not Ipsilateral Regeneration Is Responsible for Spontaneous Locomotor Recovery Post Spinal Cord Hemisection

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.730348 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yudong Cao ◽

Ya Shi ◽

Zhifeng Xiao ◽

Xi Chen ◽

Bing Chen ◽

...

Keyword(s):

Spinal Cord ◽

Medical Problem ◽

Contralateral Side ◽

Neuronal Regeneration ◽

Lesion Site ◽

Sprague Dawley ◽

Locomotor Recovery ◽

Locomotor Function ◽

Cord Injury ◽

Spinal Cord Hemisection

Spinal cord injury (SCI) usually results in permanent functional impairment and is considered a worldwide medical problem. However, both motor and sensory functions can spontaneously recover to varying extents in humans and animals with incomplete SCI. This study observed a significant spontaneous hindlimb locomotor recovery in Sprague-Dawley rats at four weeks after post-right-side spinal cord hemisection at thoracic 8 (T8). To verify whether the above spontaneous recovery derives from the ipsilateral axonal or neuronal regeneration to reconnect the lesion site, we resected either the scar tissue or right side T7 spinal cord at five weeks post-T8 hemisected injury. The results showed that the spontaneously achieved right hindlimb locomotor function had little change after resection. Furthermore, when T7 left hemisection was performed five weeks after the initial injury, the spontaneously achieved right hindlimb locomotor function was dramatically abolished. A similar result could also be observed when T7 transection was performed after the initial hemisection. The results indicated that it might be the contralateral axonal remolding rather than the ipsilateral axonal or neuronal regeneration beyond the lesion site responsible for the spontaneous hindlimb locomotor recovery. The immunostaining analyses and corticospinal tracts (CSTs) tracing results confirmed this hypothesis. We detected no substantial neuronal and CST regeneration throughout the lesion site; however, significantly more CST fibers were observed to sprout from the contralateral side at the lumbar 4 (L4) spinal cord in the hemisection model rats than in intact ones. In conclusion, this study verified that contralateral CST sprouting, but not ipsilateral CST or neuronal regeneration, is primarily responsible for the spontaneous locomotor recovery in hemisection SCI rats.

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Serotonin inhibits axonal regeneration of identifiable descending neurons after a complete spinal cord injury in lampreys

10.1101/335844 ◽

2018 ◽

Author(s):

Daniel Sobrido-Cameán ◽

Diego Robledo ◽

Laura Sánchez ◽

María Celina Rodicio ◽

Antón Barreiro-Iglesias

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Axonal Regeneration ◽

Axonal Guidance ◽

Descending Neurons ◽

Expression Of Genes ◽

Subsequent Decrease ◽

Cord Injury ◽

Key Factor ◽

Complete Spinal Cord Injury

SummaryClassical neurotransmitters are mainly known for their roles as neuromodulators, but they also play important roles in the control of developmental and regenerative processes. Here, we used the lamprey model of spinal cord injury to study the effect of serotonin in axon regeneration at the level of individually identifiable descending neurons. Pharmacological and genetic treatments after a complete spinal cord injury showed that endogenous serotonin inhibits axonal regeneration in identifiable descending neurons through the activation of serotonin 1A receptors and a subsequent decrease in cAMP levels. RNA sequencing revealed that changes in the expression of genes that control axonal guidance could be a key factor on the serotonin effects during regeneration. This study provides new targets of interest for research in non-regenerating mammalian models of traumatic CNS injuries and extends the known roles of serotonin signalling during neuronal regeneration.

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Clinical effects of intrathecal administration of expanded Wharton jelly mesenchymal stromal cells in patients with chronic complete spinal cord injury: a randomized controlled study

Cytotherapy ◽

10.1016/j.jcyt.2020.08.008 ◽

2020 ◽

Author(s):

Sergiu Albu ◽

Hatice Kumru ◽

Ruth Coll ◽

Joaquim Vives ◽

Margarita Vallés ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Intrathecal Administration ◽

Controlled Study ◽

Clinical Effects ◽

Randomized Controlled ◽

Cord Injury ◽

Complete Spinal Cord Injury

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Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury

Journal of Neurosurgery Spine ◽

10.3171/2015.9.spine15628 ◽

2016 ◽

Vol 25 (1) ◽

pp. 114-124 ◽

Cited By ~ 13

Author(s):

Sergiy V. Kushchayev ◽

Morgan B. Giers ◽

Doris Hom Eng ◽

Nikolay L. Martirosyan ◽

Jennifer M. Eschbacher ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuroprotective Effect ◽

Scar Tissue ◽

Treated Group ◽

Secondary Injury ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Cord Injury ◽

Behavioral Assessments

OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel–treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel–treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel–treated group. There was a decreased presence of inflammatory cells in the HA hydrogel–treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

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