scholarly journals Retrograde Activation of the Extrinsic Apoptotic Pathway in Spinal-Projecting Neurons after a Complete Spinal Cord Injury in Lampreys

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Antón Barreiro-Iglesias ◽  
Daniel Sobrido-Cameán ◽  
Michael I. Shifman
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Extrinsic Pathway ◽  
Apoptotic Pathway ◽  
Permanent Disability ◽  
Descending Neurons ◽  
Neuronal Soma ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition that leads to permanent disability because injured axons do not regenerate across the trauma zone to reconnect to their targets. A prerequisite for axonal regeneration will be the prevention of retrograde degeneration that could lead to neuronal death. However, the specific molecular mechanisms of axotomy-induced degeneration of spinal-projecting neurons have not been elucidated yet. In lampreys, SCI induces the apoptotic death of identifiable descending neurons that are “bad regenerators/poor survivors” after SCI. Here, we investigated the apoptotic process activated in identifiable descending neurons of lampreys after SCI. For this, we studied caspase activation by using fluorochrome-labeled inhibitors of caspases, the degeneration of spinal-projecting neurons using Fluro-Jade C staining, and the involvement of the intrinsic apoptotic pathway by means of cytochrome c and Vαdouble immunofluorescence. Our results provide evidence that, after SCI, bad-regenerating spinal cord-projecting neurons slowly degenerate and that the extrinsic pathway of apoptosis is involved in this process. Experiments using the microtubule stabilizer Taxol showed that caspase-8 signaling is retrogradely transported by microtubules from the site of axotomy to the neuronal soma. Preventing the activation of this process could be an important therapeutic approach after SCI in mammals.

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

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.

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

2019 ◽  
Vol 12 (2) ◽  
pp. dmm037085 ◽  
Author(s):  
Daniel Sobrido-Cameán ◽  
Diego Robledo ◽  
Laura Sánchez ◽  
María Celina Rodicio ◽  
Antón Barreiro-Iglesias
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Descending Neurons ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

scholarly journals Lentiviral Vectors Delivered with Biomaterials as Therapeutics for Spinal Cord Injury

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2102
Author(s):  
Ciara Shortiss ◽  
Linda Howard ◽  
Siobhan S. McMahon
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Lentiviral Vectors ◽  
Therapeutic Effects ◽  
Nucleic Acid Delivery ◽  
Permanent Disability ◽  
Cord Injury ◽  
Socioeconomic Burden ◽  
Superior Approach

Spinal cord injury (SCI) is a devastating trauma that can cause permanent disability, life-long chronic issues for sufferers and is a big socioeconomic burden. Regenerative medicine aims to overcome injury caused deficits and restore function after SCI through gene therapy and tissue engineering approaches. SCI has a multifaceted pathophysiology. Due to this, producing therapies that target multiple different cellular and molecular mechanisms might prove to be a superior approach in attempts at regeneration. Both biomaterials and nucleic acid delivery via lentiviral vectors (LVs) have proven to promote repair and restoration of function post SCI in animal models. Studies indicate that a combination of biomaterials and LVs is more effective than either approach alone. This review presents studies supporting the use of LVs and LVs delivered with biomaterials in therapies for SCI and summarises methods to combine LVs with biomaterials for SCI treatment. By summarising this knowledge this review aims to demonstrate how LV delivery with biomaterials can augment/compliment both LV and biomaterial therapeutic effects in SCI.

scholarly journals GABA promotes survival and axonal regeneration in identifiable descending neurons after spinal cord injury in larval lampreys

2018 ◽  
Author(s):  
D Romaus-Sanjurjo ◽  
R Ledo-García ◽  
B Fernández-López ◽  
K Hanslik ◽  
JR Morgan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Gabab Receptor ◽  
Gabab Receptors ◽  
Regenerative Capacity ◽  
Permanent Disability ◽  
Descending Neurons ◽  
Cord Injury

AbstractIn mammals, spinal cord injury (SCI) causes permanent disability. The poor regenerative capacity of descending neurons is one of the main causes of the lack of recovery after SCI. In addition, the prevention of retrograde degeneration leading to the atrophy or death of descending neurons is an obvious prerequisite for the activation of axonal regeneration. Lampreys show an amazing regenerative capacity after SCI. Recent histological work in lampreys suggested that GABA, which is massively released after a SCI, could promote the survival of descending neurons. Here, we aimed to study if GABA, acting through GABAB receptors, promotes the survival and axonal regeneration of descending neurons of larval sea lampreys after a complete SCI. First, we used in situ hybridization to confirm that identifiable descending neurons of late stage larvae express the gabab1 subunit of the sea lamprey GABAB receptor. We also observed an acute increase in the expression of this subunit in descending neurons after a complete SCI, which further supported the possible role of GABA and GABAB receptors in promoting the survival and regeneration of these neurons. So, we performed gain and loss of function experiments to confirm this hypothesis. Treatments with GABA and baclofen (GABAB agonist) significantly reduced caspase activation in descending neurons 2 weeks after a complete SCI. Long-term treatments with GABOB (a GABA analogue) and baclofen significantly promoted axonal regeneration of descending neurons after SCI. These data indicate that GABAergic signalling through GABAB receptors promotes the survival and regeneration of descending neurons after SCI. Finally, we used morpholinos against the gabab1 subunit to specifically knockdown the expression of the GABAB receptor in descending neurons. Long-term morpholino treatments caused a significant inhibition of axonal regeneration, which shows that endogenous GABA promotes axonal regeneration after a complete SCI in lampreys by activating GABAB receptors expressed in descending neurons. These data implicate GABAB receptors in spinal cord regeneration in lampreys and further provide a new target of interest for SCI.

Subacute posttraumatic ascending myelopathy in a 15-year-old boy

2014 ◽  
Vol 21 (3) ◽  
pp. 454-457 ◽  
Author(s):  
Timothy J. Kovanda ◽  
Eric M. Horn
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rare Event ◽  
Fracture Dislocation ◽  
Secondary Injury ◽  
Spinal Cord Trauma ◽  
Rare Occurrence ◽  
Time Period ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Secondary injury following initial spinal cord trauma is uncommon and frequently attributed to mismanagement of an unprotected cord in the acute time period after injury. Subacute posttraumatic ascending myelopathy (SPAM) is a rare occurrence in the days to weeks following an initial spinal cord injury that is unrelated to manipulation of an unprotected cord and involves 4 or more vertebral levels above the original injury. The authors present a case of SPAM occurring in a 15-year-old boy who sustained a T3–4 fracture-dislocation resulting in a complete spinal cord injury, and they highlight the imaging findings and optimum treatment for this rare event.

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