scholarly journals Noradrenergic Components of Locomotor Recovery Induced by Intraspinal Grafting of the Embryonic Brainstem in Adult Paraplegic Rats

2020 ◽  
Vol 21 (15) ◽  
pp. 5520
Author(s):  
Anna Kwaśniewska ◽  
Krzysztof Miazga ◽  
Henryk Majczyński ◽  
Larry M. Jordan ◽  
Małgorzata Zawadzka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Canal ◽  
Locomotor Performance ◽  
Adult Rats ◽  
Locomotor Recovery ◽  
Hindlimb Muscles ◽  
Hindlimb Movement ◽  
Caudal Spinal Cord ◽  
Adrenergic Receptor Agonist

Intraspinal grafting of serotonergic (5-HT) neurons was shown to restore plantar stepping in paraplegic rats. Here we asked whether neurons of other phenotypes contribute to the recovery. The experiments were performed on adult rats after spinal cord total transection. Grafts were injected into the sub-lesional spinal cord. Two months later, locomotor performance was tested with electromyographic recordings from hindlimb muscles. The role of noradrenergic (NA) innervation was investigated during locomotor performance of spinal grafted and non-grafted rats using intraperitoneal application of α2 adrenergic receptor agonist (clonidine) or antagonist (yohimbine). Morphological analysis of the host spinal cords demonstrated the presence of tyrosine hydroxylase positive (NA) neurons in addition to 5-HT neurons. 5-HT fibers innervated caudal spinal cord areas in the dorsal and ventral horns, central canal, and intermediolateral zone, while the NA fiber distribution was limited to the central canal and intermediolateral zone. 5-HT and NA neurons were surrounded by each other’s axons. Locomotor abilities of the spinal grafted rats, but not in control spinal rats, were facilitated by yohimbine and suppressed by clonidine. Thus, noradrenergic innervation, in addition to 5-HT innervation, plays a potent role in hindlimb movement enhanced by intraspinal grafting of brainstem embryonic tissue in paraplegic rats.

scholarly journals CCL3 contributes to secondary damage after spinal cord injury

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Nicolas Pelisch ◽  
Jose Rosas Almanza ◽  
Kyle E. Stehlik ◽  
Brandy V. Aperi ◽  
Antje Kroner
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Lesion Size ◽  
Secondary Injury ◽  
Wild Type ◽  
Locomotor Recovery ◽  
Secondary Damage ◽  
Cord Injury

Abstract Background Secondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress, and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (macrophage inflammatory protein 1-α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system. Methods A mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type and CCL3−/− mice. Results The expression of CCL3 and its receptors was increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size using CCL3−/− mice. CCL3−/− mice showed mild but significant improvement of locomotor recovery, a smaller lesion size and reduced neuronal damage compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced in the absence of CCL3. Conclusion We have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that CCL3 contributes to progressive tissue damage and functional impairment during secondary injury after SCI.

scholarly journals Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Krzysztof Miazga ◽  
Hanna Fabczak ◽  
Ewa Joachimiak ◽  
Małgorzata Zawadzka ◽  
Łucja Krzemień-Ojak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Functional Recovery ◽  
Serotonergic Neurons ◽  
Locomotor Recovery ◽  
Thoracic Level ◽  
Hindlimb Muscles ◽  
Complete Transection ◽  
Expression Of Genes ◽  
Influence Functional

Serotonin (5-hydroxytryptamine; 5-HT) plays an important role in control of locomotion, partly through direct effects on motoneurons. Spinal cord complete transection (SCI) results in changes in 5-HT receptors on motoneurons that influence functional recovery. Activation of 5-HT2A and 5-HT7 receptors improves locomotor hindlimb movements in paraplegic rats. Here, we analyzed the mRNA of 5-HT2A and 5-HT7 receptors (encoded by Htr2a and Htr7 genes, resp.) in motoneurons innervating tibialis anterior (TA) and gastrocnemius lateralis (GM) hindlimb muscles and the tail extensor caudae medialis (ECM) muscle in intact as well as spinal rats. Moreover, the effect of intraspinal grafting of serotonergic neurons on Htr2a and Htr7 gene expression was examined to test the possibility that the graft origin 5-HT innervation in the spinal cord of paraplegic rats could reverse changes in gene expression induced by SCI. Our results indicate that SCI at the thoracic level leads to changes in Htr2a and Htr7 gene expression, whereas transplantation of embryonic serotonergic neurons modifies these changes in motoneurons innervating hindlimb muscles but not those innervating tail muscles. This suggests that the upregulation of genes critical for locomotor recovery, resulting in limb motoneuron plasticity, might account for the improved locomotion in grafted animals.

scholarly journals Neuromodulation of motor-evoked potentials during stepping in spinal rats

2013 ◽  
Vol 110 (6) ◽  
pp. 1311-1322 ◽  
Author(s):  
Parag Gad ◽  
Igor Lavrov ◽  
Prithvi Shah ◽  
Hui Zhong ◽  
Roland R. Roy ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Evoked Potentials ◽  
Motor Evoked Potentials ◽  
Motor Task ◽  
Hindlimb Muscles ◽  
Epidural Spinal Cord Stimulation ◽  
Highly Correlated ◽  
Muscle Responses

The rat spinal cord isolated from supraspinal control via a complete low- to midthoracic spinal cord transection produces locomotor-like patterns in the hindlimbs when facilitated pharmacologically and/or by epidural electrical stimulation. To evaluate the role of epidural electrical stimulation in enabling motor control (eEmc) for locomotion and posture, we recorded potentials evoked by epidural spinal cord stimulation in selected hindlimb muscles during stepping and standing in adult spinal rats. We hypothesized that the temporal details of the phase-dependent modulation of these evoked potentials in selected hindlimb muscles while performing a motor task in the unanesthetized state would be predictive of the potential of the spinal circuitries to generate stepping. To test this hypothesis, we characterized soleus and tibialis anterior (TA) muscle responses as middle response (MR; 4–6 ms) or late responses (LRs; >7 ms) during stepping with eEmc. We then compared these responses to the stepping parameters with and without a serotoninergic agonist (quipazine) or a glycinergic blocker (strychnine). Quipazine inhibited the MRs induced by eEmc during nonweight-bearing standing but facilitated locomotion and increased the amplitude and number of LRs induced by eEmc during stepping. Strychnine facilitated stepping and reorganized the LRs pattern in the soleus. The LRs in the TA remained relatively stable at varying loads and speeds during locomotion, whereas the LRs in the soleus were strongly modulated by both of these variables. These data suggest that LRs facilitated electrically and/or pharmacologically are not time-locked to the stimulation pulse but are highly correlated to the stepping patterns of spinal rats.

Adoptive transfer of M2 macrophages promotes locomotor recovery in adult rats after spinal cord injury

2015 ◽  
Vol 45 ◽  
pp. 157-170 ◽  
Author(s):  
Shan-Feng Ma ◽  
Yue-Juan Chen ◽  
Jing-Xing Zhang ◽  
Lin Shen ◽  
Rui Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adoptive Transfer ◽  
M2 Macrophages ◽  
Adult Rats ◽  
Locomotor Recovery ◽  
Cord Injury

scholarly journals Immunization with a Neural-Derived Peptide Protects the Spinal Cord from Apoptosis after Traumatic Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Roxana Rodríguez-Barrera ◽  
Ana M. Fernández-Presas ◽  
Elisa García ◽  
Adrian Flores-Romero ◽  
Susana Martiñón ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Caspase 3 ◽  
Traumatic Injury ◽  
Functional Improvement ◽  
Control Group ◽  
Apoptotic Cells ◽  
Proinflammatory Response ◽  
Adult Rats ◽  
Necrosis Factor Alpha ◽  
Locomotor Recovery

Apoptosis is one of the most destructive mechanisms that develop after spinal cord (SC) injury. Immunization with neural-derived peptides (INDPs) such as A91 has shown to reduce the deleterious proinflammatory response and the amount of harmful compounds produced after SC injury. With the notion that the aforementioned elements are apoptotic inducers, we hypothesized that INDPs would reduce apoptosis after SC injury. In order to test this assumption, adult rats were subjected to SC contusion and immunized either with A91 or phosphate buffered saline (PBS; control group). Seven days after injury, animals were euthanized to evaluate the number of apoptotic cells at the injury site. Apoptosis was evaluated using DAPI and TUNEL techniques; caspase-3 activity was also evaluated. To further elucidate the mechanisms through which A91 exerts this antiapoptotic effects we quantified tumor necrosis factor-alpha (TNF-α). To also demonstrate that the decrease in apoptotic cells correlated with a functional improvement, locomotor recovery was evaluated. Immunization with A91 significantly reduced the number of apoptotic cells and decreased caspase-3 activity and TNF-αconcentration. Immunization with A91 also improved the functional recovery of injured rats. The present study shows the beneficial effect of INDPs on preventing apoptosis and provides more evidence on the neuroprotective mechanisms exerted by this strategy.

scholarly journals Sensory neurons contacting the cerebrospinal fluid require the Reissner fiber to detect spinal curvature in vivo

2019 ◽  
Author(s):  
Adeline Orts-Del’Immagine ◽  
Yasmine Cantaut-Belarif ◽  
Olivier Thouvenin ◽  
Julian Roussel ◽  
Asha Baskaran ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cerebrospinal Fluid ◽  
Sensory Neurons ◽  
Critical Role ◽  
Central Canal ◽  
Spinal Curvature ◽  
List Type ◽  
Close Vicinity

SummaryRecent evidence indicate active roles for the cerebrospinal fluid (CSF) on body axis development and morphogenesis of the spine implying CSF-contacting neurons (CSF-cNs) in the spinal cord. CSF-cNs project a ciliated apical extension into the central canal that is enriched in the channel PKD2L1 and enables the detection of spinal curvature in a directional manner. Dorsolateral CSF-cNs ipsilaterally respond to lateral bending while ventral CSF-cNs respond to longitudinal bending. Historically, the implication of the Reissner fiber (RF), a long extracellular thread in the CSF, to CSF-cN sensory functions has remained a subject of debate. Here, we reveal using electron microscopy in zebrafish larvae that the RF is in close vicinity with cilia and microvilli of ventral and dorsolateral CSF-cNs. We investigate in vivo the role of cilia and the Reissner fiber in the mechanosensory functions of CSF-cNs by combining calcium imaging with patch-clamp recordings. We show that disruption of cilia motility affects CSF-cN sensory responses to passive and active curvature of the spinal cord without affecting the Pkd2l1 channel activity. Since ciliary defects alter the formation of the Reissner fiber, we investigated whether the Reissner fiber contributes to CSF-cN mechanosensitivity in vivo. Using a hypomorphic mutation in the scospondin gene that forbids the aggregation of SCO-spondin into a fiber, we demonstrate in vivo that the Reissner fiber per se is critical for CSF-cN mechanosensory function. Our study uncovers that neurons contacting the cerebrospinal fluid functionally interact with the Reissner fiber to detect spinal curvature in the vertebrate spinal cord.Abstract FigureeToCThe role of the Reissner fiber, a long extracellular thread running in the cerebrospinal fluid (CSF), has been since its discovery in 1860 a subject of debate. Orts-Del’Immagine et al. report that the Reissner fiber plays a critical role in the detection of spinal curvature by sensory neurons contacting the CSF.HighlightsSince its discovery, the role of the Reissner fiber has long been a subject of debateMechanoreception in CSF-contacting neurons (CSF-cNs) in vivo requires the Reissner fiberCSF-cN apical extension is in close vicinity of the Reissner fiberCSF-cNs and the Reissner fiber form in vivo a sensory organ detecting spinal curvature

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