The effect of mesenchymal stem cell transplantation on the recovery of bladder and hindlimb function after spinal cord contusion in rats

Background  

Mesenchymal stem cells are widely used for transplantation into the injured spinal cord in vivo model and for safety, many human clinical trials are continuing to promote improvements of motor and sensory functions after spinal cord injury. Yet the exact mechanism for these improvements remains undefined. Neurogenic bladder following spinal cord injury is the main problem decreasing the quality of life for patients with spinal cord injury, but there are no clear data using stem cell transplantation for the improvement of neurogenic bladder for in vivo studies and the clinical setting.     

Intrinsic response of thoracic propriospinal neurons to axotomy

Background  

Central nervous system axons lack a robust regenerative response following spinal cord injury (SCI) and regeneration is usually abortive. Supraspinal pathways, which are the most commonly studied for their regenerative potential, demonstrate a limited regenerative ability. On the other hand, propriospinal (PS) neurons, with axons intrinsic to the spinal cord, have shown a greater regenerative response than their supraspinal counterparts, but remain relatively understudied in regards to spinal cord injury.     

MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma

Background  

Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI). The aim of this study was to investigate the neuroprotective effect of dizocilpine maleate, MK801 (2 mg/Kg, 30 min and 6 hours after injury) in a mice model of SCI. The spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy.     

Long descending cervical propriospinal neurons differ from thoracic propriospinal neurons in response to low thoracic spinal injury

Background  

Propriospinal neurons, with axonal projections intrinsic to the spinal cord, have shown a greater regenerative response than supraspinal neurons after axotomy due to spinal cord injury (SCI). Our previous work focused on the response of axotomized short thoracic propriospinal (TPS) neurons following a low thoracic SCI (T9 spinal transection or moderate spinal contusion injury) in the rat. The present investigation analyzes the intrinsic response of cervical propriospinal neurons having long descending axons which project into the lumbosacral enlargement, long descending propriospinal tract (LDPT) axons. These neurons also were axotomized by T9 spinal injury in the same animals used in our previous study.     

Electro-acupuncture promotes survival, differentiation of the bone marrow mesenchymal stem cells as well as functional recovery in the spinal cord-transected rats

Background  

Bone marrow mesenchymal stem cells (MSCs) are one of the potential tools for treatment of the spinal cord injury; however, the survival and differentiation of MSCs in an injured spinal cord still need to be improved. In the present study, we investigated whether Governor Vessel electro-acupuncture (EA) could efficiently promote bone marrow mesenchymal stem cells (MSCs) survival and differentiation, axonal regeneration and finally, functional recovery in the transected spinal cord.     

Hydroxysafflor Yellow A protects spinal cords from ischemia/reperfusion injury in rabbits

Background  

Hydroxysafflor Yellow A (HSYA), which is one of the most important active ingredients of the Chinese herb Carthamus tinctorius L, is widely used in the treatment of cerebrovascular and cardiovascular diseases. However, the potential protective effect of HSYA in spinal cord ischemia/reperfusion (I/R) injury is still unknown.     

Susceptibility weighted imaging in detecting hemorrhage in acute cervical spinal cord injury

Background and Purpose

Susceptibility weighted imaging (SWI) is sensitive to deoxyhemoglobin and blood products such as hemosiderin in detecting microbleeds in the brain. However, there are no studies on SWI in the spine cord injury so far. The purpose of this study was to evaluate the role of SWI in detecting hemorrhage in acute cervical spinal cord injury (SCI).

Materials and Methods

Twenty-three patients with a history of acute cervical spine trauma were studied. High-resolution SWI, gradient-echo (GRE) T2* weighted-image (T2*WI) and conventional magnetic resonance imaging (MRI) were performed on all patients within 15 days of the onset of injury. On the basis of the MRI findings, the patients were classified into four patterns: normal cord, spinal cord edema, spinal cord contusion and spinal cord hemorrhage. Quantitative analysis was performed by calculating and comparing the signal ratio of the hemorrhage to normal spinal cord on the same slice of T2*WI and SWI. All patients were clinically evaluated in follow-up. Twenty volunteers were also scanned as a control group.

Results

Out of 23 patients with a history of acute cervical spine trauma, 4 patients showed normal spinal cord on both conventional MRI and SWI, 8 had only spinal cord edema and 5 had contusion on conventional MRI, but SWI showed hemorrhage in 2 of the 5 patients with spinal contusion on conventional MRI; the other 6 patients had intraspinal hemorrhage on conventional MRI, and SWI proved hemorrhage in all these 6 patients. There was a significant difference between the signal ratios of hemorrhage to normal tissue on T2*WI and SWI (Z=2.34, P=.02).

Conclusion

Susceptibility weighted imaging is more sensitive than conventional MRI in detecting hemorrhage in acute cervical SCI. This technique could prove to be a useful tool in the routine evaluation of cervical SCI patients.     

Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons

Background  

Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation.     

Dorsal horn-enriched genes identified by DNA microarray, in situ hybridization and immunohistochemistry

Background  

Neurons in the dorsal spinal cord play important roles in nociception and pain. These neurons receive input from peripheral sensory neurons and then transmit the signals to the brain, as well as receive and integrate descending control signals from the brain. Many molecules important for pain transmission have been demonstrated to be localized to the dorsal horn of the spinal cord. Further understanding of the molecular interactions and signaling pathways in the dorsal horn neurons will require a better knowledge of the molecular neuroanatomy in the dorsal spinal cord.     

Anti-apoptotic and neuroprotective effects of Tetramethylpyrazine following spinal cord ischemia in rabbits

Background  

Tetramethylpyrazine (TMP) is one of the most important active ingredients of a Chinese herb Ligusticum wallichii Franchat, which is widely used in many ischemia disorders treatments. However, the exact mechanism by which TMP protects the spinal cord ischemia/reperfusion (I/R) injury is still unknown. For this purpose, rabbits were randomly divided into sham group, control group and TMP group. After the evaluation of neurologic function, the spinal cords were immediately removed for biochemical and histopathological analysis. Apoptosis was measured quantitatively by the terminal transferase UTP nick end-labeling (TUNEL) method and confirmed by electron microscopic examination, the expression of Bax and Bcl-2 was immunohistochemically evaluated and quantified by Western blot analysis.     

Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers

Background  

It has been postulated that exercise-induced activation of brain-derived neurotrophic factor (BDNF) may account for improvement of stepping ability in animals after complete spinal cord transection. As we have shown previously, treadmill locomotor exercise leads to up-regulation of BDNF protein and mRNA in the entire neuronal network of intact spinal cord. The questions arise: (i) how the treadmill locomotor training, supplemented with tail stimulation, affects the expression of molecular correlates of synaptic plasticity in spinal rats, and (ii) if a response is related to BDNF protein level and distribution.     

Phase-aligned multiple spin-echo averaging: a simple way to improve signal-to-noise ratio of in vivo mouse spinal cord diffusion tensor image

Purpose

To improve signal-noise-ratio of in vivo mouse spinal cord diffusion tensor imaging using-phase aligned multiple spin-echo technique.

Material and methods

In vivo mouse spinal cord diffusion tensor imaging maps generated by multiple spin-echo and conventional spin-echo diffusion weighting were examined to demonstrate the efficacy of multiple spin-echo diffusion sequence to improve image quality and throughput. Effects of signal averaging using complex, magnitude and phased images from multiple spin-echo diffusion weighting were also assessed. Bayesian probability theory was used to generate phased images by moving the coherent signals to the real channel to eliminate the effect of phase variation between echoes while preserving the Gaussian noise distribution. Signal averaging of phased multiple spin-echo images potentially solves both the phase incoherence problem and the bias of the elevated Rician noise distribution in magnitude image. The proposed signal averaging with Bayesian phase-aligned multiple spin-echo images approach was compared to the conventional spin-echo data acquired with doubling the scan time. The diffusion tensor imaging parameters were compared in the mouse contusion spinal cord injury. Significance level (p-value) and effect size (Cohen’s d) were reported between the control and contused spinal cord to inspect the sensitivity of each approach in detecting white matter pathology.

Results

Compared to the spin-echo image, the signal-noise-ratio increased to 1.84-fold using the phased image averaging and to 1.30-fold using magnitude image averaging in the spinal cord white matter. Multiple spin-echo phased image averaging showed improved image quality of the mouse spinal cord among the tested methods. Diffusion tensor imaging metrics obtained from multiple spin-echo phased images using three echoes and two averages closely agreed with those derived by spin-echo magnitude data with four averages (two times more in acquisition time). The phased image averaging correctly reflected pathological features in contusion spinal cord injury.

Conclusion

Our in vivo imaging results indicate that averaging the phased multiple spin-echo images yields an 84% signal-noise-ratio increase over the spin-echo images and a 41% gain over the magnitude averaged multiple spin-echo images with equal acquisition time. Current results from the animal model of spinal cord injury suggest that the phased multiple spin-echo images could be used to improve signal-noise-ratio.     

A glycine receptor is involved in the organization of swimming movements in an invertebrate chordate

Background  

Rhythmic motor patterns for locomotion in vertebrates are generated in spinal cord neural networks known as spinal Central Pattern Generators (CPGs). A key element in pattern generation is the role of glycinergic synaptic transmission by interneurons that cross the cord midline and inhibit contralaterally-located excitatory neurons. The glycinergic inhibitory drive permits alternating and precisely timed motor output during locomotion such as walking or swimming. To understand better the evolution of this system we examined the physiology of the neural network controlling swimming in an invertebrate chordate relative of vertebrates, the ascidian larva Ciona intestinalis.     

<Emphasis Type="Italic">Ex vivo</Emphasis> infection of human embryonic spinal cord neurons prior to transplantation into adult mouse cord

Background  

Genetically modified pseudorabies virus (Prv) proved suitable for the delivery of foreign genes to rodent embryonic neurons ex vivo and maintaining foreign gene expression after transplantation into spinal cord in our earlier study. The question arose of whether human embryonic neurons, which are known to be more resistant to Prv, could also be infected with a mutant Prv. Specifically, we investigated whether a mutant Prv with deleted ribonucleotide reductase and early protein 0 genes has the potential to deliver marker genes (gfp and β-gal) into human embryonic spinal cord neurons and whether the infected neurons maintain expression after transplantation into adult mouse cord.     

Differential effects of intragastric acid and capsaicin on gastric emptying and afferent input to the rat spinal cord and brainstem

Background  

Hydrochloric acid (HCl) is a potential threat to the integrity of the gastric mucosa and is known to contribute to upper abdominal pain. We have previously found that gastric mucosal challenge with excess HCl is signalled to the rat brainstem, but not spinal cord, as visualized by expression of c-fos messenger ribonucleic acid (mRNA), a surrogate marker of neuronal excitation. This study examined whether gastric mucosal exposure to capsaicin, a stimulant of nociceptive afferents that does not damage the gastric mucosa, is signalled to both brainstem and spinal cord and whether differences in the afferent signalling of gastric HCl and capsaicin challenge are related to different effects on gastric emptying.     

Foxo3a induces motoneuron death through the Fas pathway in cooperation with JNK

Background  

Programmed cell death of motoneurons in the developing spinal cord is thought to be regulated through the availability of target-derived neurotrophic factors. When deprived of trophic support, embryonic spinal motoneurons in vitro over-express FasL, a ligand activating a Fas-mediated death pathway. How trophic factors regulate the expression of FasL is presently unclear, but two regulators of FasL, FOXO3a (FKHRL1) and JNK have been described to play a role in other cell types. Thus, their potential function in motoneurons was investigated in this study.     

Differential inhibition of postnatal brain,spinal cord and body growth by a growth hormone antagonist

Background  

Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). In this study, we use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. The GHA transgene encodes a protein that inhibits the binding of GH to its receptor, specifically antagonizing the trophic effects of endogenous GH.