scholarly journals Intermittent hypoxia promotes recovery of respiratory motor function in spinal cord-injured mice depleted of serotonin in the central nervous system

2016 ◽  
Vol 121 (2) ◽  
pp. 545-557 ◽  
Author(s):  
Dragana Komnenov ◽  
Julia Z. Solarewicz ◽  
Fareeza Afzal ◽  
Kwaku D. Nantwi ◽  
Donald M. Kuhn ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Motor Function ◽  
Intermittent Hypoxia ◽  
Partial Recovery ◽  
Breathing Frequency ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Diaphragm Activity

We examined the effect of repeated daily exposure to intermittent hypoxia (IH) on the recovery of respiratory and limb motor function in mice genetically depleted of central nervous system serotonin. Electroencephalography, diaphragm activity, ventilation, core body temperature, and limb mobility were measured in spontaneously breathing wild-type (Tph2+/+) and tryptophan hydroxylase 2 knockout (Tph2−/−) mice. Following a C2 hemisection, the mice were exposed daily to IH (i.e., twelve 4-min episodes of 10% oxygen interspersed with 4-min normoxic periods followed by a 90-min end-recovery period) or normoxia (i.e., sham protocol, 21% oxygen) for 10 consecutive days. Diaphragm activity recovered to prehemisection levels in the Tph2+/+ and Tph2−/− mice following exposure to IH but not normoxia [Tph2+/+ 1.3 ± 0.2 (SE) vs. 0.3 ± 0.2; Tph2−/− 1.06 ± 0.1 vs. 0.3 ± 0.1, standardized to prehemisection values, P < 0.01]. Likewise, recovery of tidal volume and breathing frequency was evident, although breathing frequency values did not return to prehemisection levels within the time frame of the protocol. Partial recovery of limb motor function was also evident 2 wk after spinal cord hemisection. However, recovery was not dependent on IH or the presence of serotonin in the central nervous system. We conclude that IH promotes recovery of respiratory function but not basic motor tasks. Moreover, we conclude that spontaneous or treatment-induced recovery of respiratory and motor limb function is not dependent on serotonin in the central nervous system in a mouse model of spinal cord injury.

scholarly journals Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury

RSC Advances ◽  
2020 ◽  
Vol 10 (32) ◽  
pp. 18677-18686
Author(s):  
Jia Liu ◽  
Kai Li ◽  
Ke Huang ◽  
Chengliang Yang ◽  
Zhipeng Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Traumatic Injury ◽  
High Rate ◽  
Plga Microspheres ◽  
Cord Injury ◽  
The Central Nervous System

Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery.

Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system

Spinal Cord ◽  
2020 ◽  
Vol 58 (12) ◽  
pp. 1235-1248
Author(s):  
M. J. Mulcahey ◽  
Linda A. T. Jones ◽  
Frank Rockhold ◽  
Rϋediger Rupp ◽  
John L. K. Kramer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Nervous System ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Adaptive Trial

scholarly journals An Optimal Protocol to Analyze the Rat Spinal Cord Proteome

2009 ◽  
Vol 4 ◽  
pp. BMI.S2965 ◽  
Author(s):  
F. Gil-Dones ◽  
S. Alonso-Orgaz ◽  
G. Avila ◽  
T. Martin-Rojas ◽  
V. Moral-Darde ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Protein Separation ◽  
Protein Extraction ◽  
Total Protein Content ◽  
Cord Injury ◽  
Optimal Protocol ◽  
The Central Nervous System

Since the function of the spinal cord depends on the proteins found there, better defing the normal Spinal Cord Proteome is an important and challenging task. Although brain and cerebrospinal fluid samples from patients with different central nervous system (CNS) disorders have been studied, a thorough examination of specific spinal cord proteins and the changes induced by injury or associated to conditions such as neurodegeneration, spasticity and neuropathies has yet to be performed. In the present study, we aimed to describe total protein content in the spinal cord of healthy rats, employing different proteomics tools. Accordingly, we have developed a fast, easy, and reproducible sequential protocol for protein extraction from rat spinal cords. We employed conventional two dimensional electrophoresis (2DE) in different pH ranges (eg. 4–7, 3–11 NL) combined with identification by mass spectrometry (MALDI-TOF/TOF), as well as first dimension protein separation combined with Liquid Chromatography Mass Spectrometry/Mass Spectrometry (LC-MS/MS) to maximise the benefits of this technology. The value of these techniques is demonstrated here by the identification of several proteins known to be associated with neuroglial structures, neurotransmission, cell survival and nerve growth in the central nervous system. Furthermore this study identified many spinal proteins that have not previously been described in the literature and which may play an important role as either sensitive biomarkers of dysfunction or of recovery after Spinal Cord Injury.

scholarly journals Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system

2003 ◽  
Vol 162 (2) ◽  
pp. 233-243 ◽  
Author(s):  
Catherine I. Dubreuil ◽  
Matthew J. Winton ◽  
Lisa McKerracher
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axon Growth ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Cord Injury ◽  
The Central Nervous System

Growth inhibitory proteins in the central nervous system (CNS) block axon growth and regeneration by signaling to Rho, an intracellular GTPase. It is not known how CNS trauma affects the expression and activation of RhoA. Here we detect GTP-bound RhoA in spinal cord homogenates and report that spinal cord injury (SCI) in both rats and mice activates RhoA over 10-fold in the absence of changes in RhoA expression. In situ Rho-GTP detection revealed that both neurons and glial cells showed Rho activation at SCI lesion sites. Application of a Rho antagonist (C3–05) reversed Rho activation and reduced the number of TUNEL-labeled cells by ∼50% in both injured mouse and rat, showing a role for activated Rho in cell death after CNS injury. Next, we examined the role of the p75 neurotrophin receptor (p75NTR) in Rho signaling. After SCI, an up-regulation of p75NTR was detected by Western blot and observed in both neurons and glia. Treatment with C3–05 blocked the increase in p75NTR expression. Experiments with p75NTR-null mutant mice showed that immediate Rho activation after SCI is p75NTR dependent. Our results indicate that blocking overactivation of Rho after SCI protects cells from p75NTR-dependent apoptosis.

scholarly journals Investigating Mimetics of a Peptide Derived from the Effector Domain of MARCKS as Possible Therapeutics for Spinal Cord Injury

2021 ◽  
Vol 1 (3) ◽  
Author(s):  
Monica Tschang ◽  
Melitta Schachner
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Female Mice ◽  
Blood Brain ◽  
Cord Injury ◽  
The Central Nervous System

Like other conditions affecting the central nervous system, spinal cord injury (SCI) is difficult to treat with molecular therapies because the blood-brain barrier makes intravenous treatments largely ineffective. For example, a synthetic peptide chain derived from the effector domain (ED) of myristoylated alanine-rich C-kinase substrate (MARCKS) has been found to improve functional recovery after SCI in female mice; however, peptides do not always pass the blood-brain barrier and are easily degraded due to natural proteases and are excreted during kidney filtration. Therefore, the ED peptide cannot access the central nervous system to exhibit its effects if administered intravenously. Instead of injecting the ED peptide into the bloodstream, we propose to find compounds that can pass the blood-brain barrier in place of the ED peptide, improving treatment compatibility. To find such alternatives, we screened compound libraries via competitive enzyme-linked immunosorbent assay (ELISA) and identified five potential ED peptide mimetics—compounds that mimic the structure and function of the ED peptide. We then used another competitive ELISA to verify their structural similarity to the peptide. After performing toxicity tests to determine the appropriate concentrations of the mimetics to use in functional assays, we found that all five mimetics trigger a significant increase in neurite length in neurons from female mice, but not male mice, when compared to the vehicle control solution. Although more functional tests are necessary, these results suggest that these mimetics trigger ED peptide functions and may provide a more efficient treatment alternative for SCI.

scholarly journals Cosine tuning determines plantarflexors' activities during human upright standing and is affected by incomplete spinal cord injury

2020 ◽  
Author(s):  
Kai Lon Fok ◽  
Jae W Lee ◽  
Janelle Unger ◽  
Katherine Chan ◽  
Daichi Nozaki ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Knee Extension ◽  
Medial Gastrocnemius ◽  
Quiet Standing ◽  
Incomplete Spinal Cord Injury ◽  
Cord Injury ◽  
The Central Nervous System

Plantarflexors such as the soleus (SOL) and medial gastrocnemius (MG) play key roles in controlling bipedal stance; however, how the central nervous system controls the activation levels of these plantarflexors is not well understood. Here we investigated how the central nervous system controls the plantarflexors' activation level during quiet standing in a cosine tuning manner where the maximal activation is achieved in a preferred direction (PD). Further, we investigated how spinal cord injury affects these plantarflexors' activations. Thirteen healthy adults (AB) and thirteen individuals with chronic, incomplete spinal cord injury (iSCI) performed quiet standing trials. Their body kinematics, kinetics as well as electromyography signals from the MG and SOL were recorded. In the AB-group, we found that the plantarflexors followed the cosine tuning manner during quiet standing. That is, MG was most active when the ratio of plantarflexion torque to knee extension torque was approximately 2:-3, while SOL was most active when the ratio was approximately 2:1. This suggests that the SOL muscle despite being a monoarticular muscle is sensitive to both ankle plantarflexion and knee extension during quiet standing. The difference in the PDs accounts for the phasic activity of MG and for the tonic activity of SOL. Unlike the AB-group, the MG's activity was similar to the SOL's activity in the iSCI-group, and the SOL PDs were similar to the ones in the AB-group. This result suggests that chronic iSCI affects the control strategy, i.e., cosine tuning, for MG, which may affect standing balance in individuals with iSCI.

Specific conditions

2012 ◽  
Author(s):  
Rob Forsyth ◽  
Richard Newton
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Autoimmune Disease ◽  
Demyelinating Disease ◽  
Acquired Brain Injury ◽  
Cord Injury ◽  
The Disabled ◽  
The Central Nervous System

Acquired brain injury 210Acquired spinal cord injury 215Autoimmune disease of the central nervous system 218‘Autoinflammatory’ conditions 223Autoimmune encephalitides 224Cerebral palsies 227Care of the disabled child 240Feeding 248Communication 251Special senses 252Respiratory disease in neurodisability 254Demyelinating disease ...

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