Spinal cord infarction in disease and surgery of the aorta

Diseases of the aorta and surgery of the aorta can produce spinal cord damage. There are major variations in blood supply to the spinal cord between individuals. The spinal cord may be tamponaded by increased spinal fluid pressure subsequent to clamping the aorta. Both of these factors may contribute to spinal cord infarction. The available methods and procedures to protect the spinal cord during surgery are discussed.     

Spinal Cord Contusion

Spinal cord injury is a major cause of disability with devastating neurological outcomes and lim-ited therapeutic opportunities, even though there are thousands of publications on spinal cord injury annually. There are two major types of spinal cord injury, transaction of the spinal cord and spinal cord contusion. Both can theoretically be treated, but there is no well documented treatment in human being. As for spinal cord contusion, we have developed an operation with fabulous result.     

Construction of spinal cord cDNA library and application for subtractive cloning of spinal cord-specific cDNAs

Neurodegenerative diseases are characterized by neuronal degeneration of specific neurons, e.g., degeneration of motoneurons in amyotrophic lateral sclerosis. As an approach to understand molecular mechanisms of neuronal degeneration of human spinal cord motoneurons in various motor neuron diseases, we have constructed a human spinal cord cDNA library and developed a strategy for isolating spinal cord-specific genes by subtractive cloning. We constructed human spinal cord and brain cDNA libraries from postmortem human spinal cord and brain. To isolate human spinal cord-specific cDNAs, a spinal cord-enriched [³²P]cDNA probe was generated by the phenol emulsion reassociation technique. Forty-eight cDNA clones out of 10,000 colonies gave strong signals with the subtracted probe, and individual spinal cord cDNA clones were isolated. Northern blotting analysis confirmed that two spinal cord cDNA clones are, in fact, more abundant in spinal cord compared to brain.     

Pain, nociception and spinal opioid receptors

1. Opioid peptides derived from proenkephalin and prodynorphin are differentially distributed in the spinal cord. Proenkephalin peptides are preferentially located in the sacral portion of the cord while prodynorphin peptides are concentrated in the cervical spinal cord.

2. μ opioid receptor are highly concentrated in superficial layers of the dorsal horn in all the spinal cord.

3. δ opioid receptor are more diffusely distributed in the gray matter of the spinal cord. These sites are principally located in cervical and thoracic portions of the spinal cord.

4. κ opioid receptors are highly concentrated in the superficial layers of the lumbo-sacral spinal cord. Its density decreased in the upper levels of the spinal cord.

5. It appears that μ opioid receptors are indifferentially activated by thermal, pressure and visceral nociceptive inputs. δ receptors are more likely to be involved in thermal nociception while κ opioid binding sites are associated to visceral pain nociceptive inputs.     

Primary spinal cord oligodendroglioma. Case illustration

Spinal cord oligodendrogliomas are rare pathologies of the spinal cord, and their location at conus and/or filum terminale is even rarer. There are only 7 spinal cord oligodendrogliomas reported in the literature. Our case is the eighth spinal cord oligodendrogliomas at this location.     

A progressive compression model of thoracic spinal cord injury in mice: function assessment and pathological changes in spinal cord

Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few are available for mice. Our aim is to develop a thoracic progressive compression mice model of spinal cord injury. In this study, adult wild-type C57BL/6 mice were divided into two groups: in the surgery group, a screw was inserted at T9 lamina to compress the spinal cord, and the compression was increased by turning it further into the canal (0.2 mm) post-surgery every 2 weeks up to 8 weeks. In the control group, a hole was drilled into the lamina without inserting a screw. The results showed that Basso Mouse Scale scores were lower and gait worsened. In addition, the degree of hindlimb dysfunction in mice was consistent with the degree of spinal cord compression. The number of motor neurons in the anterior horn of the spinal cord was reduced in all groups of mice, whereas astrocytes and microglia were gradually activated and proliferated. In conclusion, this progressive compression of thoracic spinal cord injury in mice is a preferable model for chronic progressive spinal cord compression injury.     

Epidural electrical stimulation for spinal cord injury

A long-standing goal of spinal cord injury research is to develop effective repair strategies, which can restore motor and sensory functions to near-normal levels. Recent advances in clinical management of spinal cord injury have significantly improved the prognosis, survival rate and quality of life in patients with spinal cord injury. In addition, a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord injury. Such efforts enabled the development of pharmacologic agents, biomaterials and stem-cell based therapy. Despite these efforts, there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal cord. These challenges led to an increased focus on another therapeutic approach, namely neuromodulation. In multiple animal models of spinal cord injury, epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function. Emerging evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord injury. However, most clinical studies were conducted on a very small number of patients with a wide range of spinal cord injury. Thus, subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation parameters. Here, we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord injury. We also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.     

Assessment of spinal cord damage in MS using MRI

Spinal cord imaging is important in the evaluation of patients with MS. There are several techniques available which provide satisfactory images of lesions in the spinal cord. Conventional measures used in the assessment of damage to the spinal cord include quantification of: (1) high intensity on T2 weighted images; (2) spinal cord enhancement; and (3) spinal cord atrophy. Although not presently implemented, newer methods including magnetization transfer, diffusion, and proton spectroscopy offer the potential for more specific classification of spinal cord MS. Assessment of spinal cord damage using MR still remains behind the development of brain methodology and represents both a challenge and an opportunity.     

Neuropeptide Y mRNA expression in interneurons in rat spinal cord.

Neuropeptide Y (NPY)-immunoreactive axons are present within the spinal cord. Some of these axons originate from neurons in the brainstem. Other axons arise from within the spinal cord since NPY-immunoreactivity can be detected after complete spinal cord transection. To identify spinal neurons that might express NPY, we localized NPY mRNA in rat spinal cord using in situ hybridization histochemistry. NPY mRNA-containing neurons were localized in the dorsal horn, in medial laminae of the grey matter and in the lateral spinal nucleus in thoracic, lumbar and sacral cord. The location of some of these neurons, and their proximity to sympathetic preganglionic neurons, suggest some NPY-containing interneurons are likely to be involved in spinal as well as supraspinal autonomic reflex pathways.     

Prognostic value of spinal cord MRI in multiple sclerosis patients

Multiple sclerosis [MS] is a common inflammatory, demyelinating and neurodegenerative disease of the central nervous system that affects both the brain and the spinal cord. In clinical practice, spinal cord MRI is performed far less frequently than brain MRI, mainly owing to technical limitations and time constraints. However, improvements of acquisition techniques, combined with a strong diagnosis and prognostic value, suggest an increasing use of spinal cord MRI in the near future. This review summarizes the current data from the literature on the prognostic value of spinal cord MRI in MS patients in the early and later stages of their disease. Both conventional and quantitative MRI techniques are discussed. The prognostic value of spinal cord lesions is clearly established at the onset of disease, underlining the interest of spinal cord conventional MRI at this stage. However, studies are currently lacking to affirm the prognostic role of spinal cord lesions later in the disease, and therefore the added value of regular follow-up with spinal cord MRI in addition to brain MRI. Besides, spinal cord atrophy, as measured by the loss of cervical spinal cord area, is also associated with disability progression, independently of other clinical and MRI factors including spinal cord lesions. Although potentially interesting, this measurement is not currently performed as a routine clinical procedure. Finally, other measures extracted from quantitative MRI have been established as valuable for a better understanding of the physiopathology of MS, but still remain a field of research.     

Innervation of the spinal cord by sympathetic fibers

Pharmacologic and neurochemical studies suggest that catecholamines are still present below the level of transection in the spinal cord of the chronic spinal animal, despite the degeneration of bulbospinal catecholamine pathways. Histofluorescence studies of rat and dog spinal cord revealed noradrenergic fibers and varicosities remaining in the chronically decentralized spinal cord which can account for the low concentrations of norepinephrine (NE) found below the transection. The fibers appear to enter the spinal cord with blood vessels through the anterior median fissure, and are probably of sympathetic origin. In the spinal cord, these fibers can dissociate from blood vessels and continue through the neuropil; they are associated with neurons in the ventral horn and occasionally in the central gray. These peripheral sympathetic fibers may influence motor systems and other nervous functions.     

Serotonin and norepinephrine in the spinal cord of man

The content of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) was analysed in 71 human spinal cords obtained post-mortem. The highest content of 5-HT, 5-HIAA and NE was found in the lumbar enlargement of the spinal cord. 5-HT and 5-HIAA content increased from fetal to adult spinal cord whereas the content of NE decreased. Characteristic segmental distribution of measured monoamines was present in adult spinal cord only. In two patients spinal cord lesion led to the reduction in spinal cord content of 5-HT, 5-HIAA and NE and loss of characteristic segmental distribution of these substances. These results are in general agreement with observations on spinal cord of different animal species.     

Imaging of the spine in multiple sclerosis

The spinal cord is a common site of involvement in multiple sclerosis (MS), and a major cause of the disability suffered by MS patients. High quality MR imaging of the spinal cord is therefore important for diagnosis and research. Imaging of the spine, however, presents many technical difficulties because of the small size of the spinal cord and the potential for artifacts. This article discusses technical difficulties such as pulse sequences, the use of newer imaging techniques, and the application of spinal MR imaging in clinical settings. Major studies are underway involving spinal cord imaging, and clinical trials of disease-modifying agents are beginning to include spinal cord imaging, especially measurements of atrophy, as part of their protocols. In clinical practice, spinal cord imaging is essential for ruling out other causes of myelopathies, particularly spinal cord compression, and can help in the diagnosis of MS when brain imaging is normal, or in older individuals in whom findings in the brain are less specific.     

Evidence for functional contact between cografted locus coeruleus and spinal cord in oculo: electrophysiological studies

The functional consequences of the locus coeruleus innervation of the spinal cord are not yet clearly understood. In a recent histological study it was shown that intraocular spinal cord grafts will become innervated by tyrosine hydroxylase-positive nerve fibers from a cografted locus coeruleus. In the present study we use this intraocular model of the descending coeruleo-spinal pathway to investigate functional contact between locus coeruleus and the spinal cord. We have pharmacologically characterized the receptor mediation of norepinephrine-induced, as well as locus coeruleus-mediated depressions of spinal cord neurons grafted in oculo. We found that electrical stimulation of the locus coeruleus part of the double grafts predominantly caused an inhibition of cografted spinal cord neurons. Norepinephrine-induced inhibition of the firing rate of single grafted spinal cord neurons was antagonized by phentolamine, an alpha-adrenergic antagonist, but was unaffected by timolol, a beta-adrenergic antagonist. Similarly, inhibition of the firing rate of grafted spinal cord neurons by stimulation of cografted locus coeruleus was antagonized by phentolamine but not by timolol. Interestingly, single spinal cord grafts were more sensitive to the depressant effects of perfused norepinephrine than was the spinal cord cografted with locus coeruleus. We conclude that spinal cord grafts can be functionally innervated by cografted locus coeruleus and that the noradrenergic inputs to spinal cord from cografted locus coeruleus are alpha-adrenergically mediated. Furthermore, the postsynaptic receptors in single spinal cord grafts appear to be supersensitive to norepinephrine application.     

Spinal cord ischemia

Traditional data and recent advances in the field of spinal cord ischemia are reviewed, with special attention to clinical and radiological features, as well as underlying etiology, outcome, and pathophysiology. Acute spinal cord ischemia includes arterial and venous infarction and global ischemia resulting from cardiac arrest or severe hypotension. MRI has become the technique of choice for the imaging diagnosis of spinal cord infarction. Correlation of clinical and MRI data has allowed diagnosis of clinical syndromes due to small infarcts in the central or peripheral arterial territory of the spinal cord. Diffusion-weighted MR imaging may increase the sensitivity and specificity for diagnosis of acute spinal cord infarction. Diagnosis of venous spinal cord infarction remains difficult. As for global ischemia, neuropathological studies demonstrated a great sensitivity of spinal cord to ischemia, with selective vulnerability of lumbosacral neurons. Chronic spinal cord ischemia results in a syndrome of progressive myelopathy. The cause is usually an arteriovenous malformation. Most often, diagnosis may be suspected on MRI, leading to diagnostic, and eventually therapeutic, spinal angiography.     

Ascending tract neurons survive spinal cord transection in the neonatal rat

Retrograde axonal transport was used to determine which ascending nerve tracts from the lumbosacral spinal cord are present in the cervical spinal cord of the newborn rat and if their cell bodies survive axotomy. A pledget of true blue was applied to a low cervical spinal transection in the newborn rat (N = 4). After a 5-day survival period, neurons were labeled in the laminae of origin of all ascending nerve tracts throughout the lumbosacral spinal cord. Neurons labeled in the same way survived for at least 1 month postoperatively when the spinal cord was transected at a midthoracic level at 5 days of age (N = 4). No neurons in the lumbosacral spinal cord were labeled if the midthoracic spinal cord was transected at the same time as application of the dye to cervical spinal cord (N = 2). Therefore, neurons labeled with true blue from cervical spinal cord during the neonatal period are likely to have been axotomized by thoracic injury made at 5 days of age. Three months after midthoracic spinal transection of newborn rats, HRP was injected or a pledget was applied to the first spinal segment caudal to this lesion (N = 8). The same population of neurons was labeled as in adult rats receiving application of HRP to an acute midthoracic spinal transection (N = 4). Neurons were seldom labeled in adult rats in which HRP was injected and ascending nerve tract axons not damaged (N = 4). These results suggest that most ascending nerve tract axons are present in cervical spinal cord during the neonatal period (by 4 to 5 days of age).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nestin-positive cells in the spinal cord: a potential source of neural stem cells

Some literatures have reported neural precursor cells (NPCs) exist in spinal cord of adult mammal, however, the NPCs distribution feature in spinal cord of adult mice so far is not described in detail. In order to observe and compare the distribution feature of NPCs in various spinal cord regions of adult mice, to research a potential source of neural stem cells (NSCs), we obtained NPCs distribution feature by analyzing the distribution of the nestin-containing cells (NCCs) in spinal cord of adult nestin second-intron enhancer controlled LacZ reporter transgenic mice (pNes-Tg) with LacZ staining and positive cell quantification. The results showed that: NCCs were observed in various regions of spinal cord of adult mice, but amount of NCCs was different in distinct region, the rank order of NCCs amount in various spinal cord regions was dorsal horn region greater than central canal greater than the ventral and lateral horn. NCCs in dorsal horn region mainly distributed in substantia gelatinosa, NCCs in central canal mainly distributed in ependymal zone, on the contrary, NCCs in ventral, lateral horn, medullae, nucleus regions of spinal cord were comparatively less. The rank order of NCCs amount in various spinal cord segments was cervical segment greater than lumbar sacral segment greater than thoracic segment. There was no significantly difference between NCCs amount in the left and right sides, and within cervical 1–7, thoracic 1–12, lumbar 1–5, sacral segment of spinal cord in adult mice. These data collectively indicate that NPCs extensively distribute in various regions of spinal cord of adult mice, especially in substantia gelatinosa and ependymal zone. NPCs in cervical segment are abundant, NPCs in thoracic segment are the least while compared the different spinal cord segment, the NPCs in various regions of spinal cord of adult mice are a potential source of NSCs.     

A second traumatic spinal cord injury: associated risk factors. Case report and review.

Despite advances in acute care and long term management, traumatic spinal cord injury remains a devastating and disabling event. This report describes the case of a second traumatic spinal cord injury in a previously rehabilitated and functionally independent paraplegic. Factors potentially associated with the second spinal cord injury in this patient include wheelchair use, previous spinal fusion, alcohol use and sensation-seeking behavior. These factors, which are common to many spinal cord injured patients, could potentially be risk factors for a second traumatic spinal injury.     

Differences in neuroplasticity after spinal cord injury in varying animal models and humans

Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without therapeutic interventions, as assessed by the Basso, Beattie and Bresnahan locomotor scale. However, many human patients suffer from permanent loss of motor function following spinal cord injury. While rats are the most understood animal model, major differences in sensorimotor pathways between quadrupeds and bipeds need to be considered. Understanding the major differences between the sensorimotor pathways of rats, non-human primates, and humans is a start to improving targets for treatments of human spinal cord injury. This review will discuss the neuroplasticity of the brain and spinal cord after spinal cord injury in rats, non-human primates, and humans. A brief overview of emerging interventions to induce plasticity in humans with spinal cord injury will also be discussed.