Spinal cord injury is a severe central nervous system disease, which will cause a series of complex pathophysiological changes and activate a variety of signaling pathways including Notch signaling. Studies have evidenced that activation of the Notch signaling pathway is not conducive to nerve repair and symptom improvement after spinal cord injury. Its mechanisms include inhibiting neuronal differentiation and axon regeneration, promoting reactive astrocyte proliferation, promoting M1 macrophage polarization and the release of proinflammatory factors, and inhibiting angiogenesis. Therefore, it has become a promising therapeutic strategy to inhibit Notch signal as a target in the treatment of spinal cord injury. In recent years, some researchers have used drugs, cell transplantation or genetic modification to regulate Notch signaling, which can promote the recovery of nerve function after spinal cord injury, thereby providing new treatment strategies for the treatment of spinal cord injury. This article will summarize the mechanism of Notch signaling pathway in spinal cord injury, and at the same time review the research progress in the treatment of spinal cord injury by modulating Notch signaling pathway in recent years, so as to provide new research ideas for further exploring new strategies for spinal cord injury.
Axons/metabolism* ; Cell Transplantation ; Humans ; Nerve Regeneration ; Signal Transduction/genetics* ; Spinal Cord/metabolism* ; Spinal Cord Injuries/metabolism*

It is the purpose of this study to determine the alterations of the metabolism on the feline spinal cord following trauma. Cats were anesthetized with ketamine hydrocloride and injured with a 400 gm-cm impact injury to L-2 level of spinal cord. Biochemical analysis of the injured segment revealed signicifant depletion in the concentrations of adenosine triphosphate(ATP) for the entire 24-hour postinjury period. Glucose concentrations were elevated significantly for the entire 24-hour period, and especially marked elevated between 8 and 24 hours. Lactate concentrations were elevated at 1 hour and between 1 and 4 hours. but especially significantly declined between 8 and 24 hours. This sequence of the metabolic changes suggested that anaerobic metabolism likely predominated for the initial 4 hours, and between 8 and 24 hours there appeared to be an increasing percentage of oxidative metabolism in the remaining metabolically viable tissues.
Adenosine ; Adenosine Triphosphate ; Animals ; Cats ; Energy Metabolism* ; Glucose ; Ketamine ; Lactic Acid ; Metabolism ; Spinal Cord Injuries* ; Spinal Cord*

Animals ; Gene Expression ; Mice ; Mice, Inbred Strains ; Spinal Cord ; metabolism ; Spinal Cord Injuries ; genetics ; metabolism ; p21-Activated Kinases ; genetics

OBJECTIVETo quantitatively analyze the temporal and spatial pattern of RhoA expression in injured spinal cord of adult mice.

METHODSA spinal cord transection model was established in adult mice. At 1, 3, 7, 14, 28, 56 and 112 days after the surgery, the spinal cords were dissected and cryosectioned for RhoA/NF200, RhoA/GFAP, RhoA/CNPase or RhoA/IBA1 double fluorescent immunohistochemistry to visualize RhoA expressions in the neurons, astrocytes, oligodendrocytes and microglia. The percentages as well as the immunostaining intensities of RhoA-positive cells in the parenchymal cells were quantitatively analyzed.

RESULTSRhoA was weakly expressed in a few neurons and oligodendrocytes in normal spinal cord. After spinal cord injury, the percentage of RhoA-positive cells and RhoA expression intensity in the spinal cord increased and peaked at 7 days post injury (dpi) in neurons, oligodendrocytes and astrocytes, followed by a gradual decrease till reaching a low level at 112 dpi. In the microglia, both the RhoA-positive cells and RhoA expression intensity reached the maximum at 14 dpi and maintained a high level till 112 dpi.

CONCLUSIONTraumatic spinal cord injury can upregulate RhoA expression in the neurons as well as all the glial cells in the spinal cord. RhoA expression patterns vary with post-injury time, location and among different parenchymal cells in the injured spinal cord.

Animals ; Astrocytes ; metabolism ; Female ; Mice ; Mice, Inbred Strains ; Microglia ; metabolism ; Neuroglia ; metabolism ; Neurons ; metabolism ; Spinal Cord ; metabolism ; Spinal Cord Injuries ; metabolism ; rho GTP-Binding Proteins ; metabolism

Spinal cord injury causes a decrease in bone mass, an osteopenia and an increased risk of fractures. In this condition, previous histomorphologic and biochemical reports have shown an uncoupling between bone formations and resorptions, however the exact sequence of events resulting in bone loss is still not fully understood. Since accurate and sensitive techniques have become available recently to assess bone metabolism, more informations are now available regarding the bone loss in paralysed or immobilized individuals. The purpose of this study is to clarify the changes of biochemical markers and bone densities. Ten complete and 10 incomplete spinal cord injury patients were enrolled for this study. The bone density of femur and lumbar vertebra, and the biochemical markers such as serum osteocalcin and urine deoxypyridinoline were measured. Results were analyzed by Mann-Whitney method and Pearson's correlation of SPSS PC program. Comparing with normal values, in the spinal cord injury groups, the values of serum osteocalcin were elevated (p>0.05), and also the values of urine deoxypyridinoline were significantly elevated(p<0.05). The duration after spinal cord injury and the bone density of femur and lumbar vertebra showed a moderate negative correlation (Pearson's R: +/-0.47, +/-0.43, respectively)(p<0.05). In conclusion, the results of increased values of biochemical markers in bone metabolism support that the bone turn-over rate increases after the spinal cord injury.
Biomarkers ; Bone Density ; Bone Diseases, Metabolic ; Femur ; Humans ; Metabolism* ; Osteocalcin ; Reference Values ; Spinal Cord Injuries ; Spinal Cord* ; Spine

One of the sequelae of spinal cord trauma which start soon after the onset of injury is the loss of the calcium from bone. Bone mineral and matrix resorption causes negative calcium balance, and eventually osteoporosis. Etidronate disodium(etidronate) is an oral diphosphonate compound known to reduce bone resorption through the inhibition of osteoclasic activity. Since continuous oral treatment with high doses of etidronate may lead to the impairment of bone mineralization and the cessation of bone remodeling, a ideal therapeutic regimen consist of the intermittent cyclical administration of the diphosphonate in a dose that inhibits bone resorption. To assess the effect of etidronate on bone metabolism and bone mineral density after spinal cord injury, we studied two groups of 7 spinal cord injury(SCI) patients with etidronate and 7 SCI patients without etidronate. Seven patients of treatment group received oral etidronate (5 mg/kg/day) for 2 weeks followed by a 10-week period in which no drugs were given. This sequence was repeated 4 times, for a total of 48 weeks. The results showed that the patients receiving etidronate had siginificant decrease in the serum osteocalcin(OC), urine deoxypyridinoline(D-PYD) level but no increase in their mean bone density. We can carefully conclude that intermittent cyclical therapy with etidronate siginificantly reduces bone metabolic rate and inhibit bone mineral loss on osteoporosis in spinal cord injury patients.
Bone Density ; Bone Remodeling ; Bone Resorption ; Calcification, Physiologic ; Calcium ; Etidronic Acid* ; Humans ; Metabolism ; Osteoporosis* ; Spinal Cord Injuries* ; Spinal Cord*

Significant illnesses or a major trauma including spinal cord injury can induce the changes of thyroid hormone metabolism, leading to the findings of "Euthyroid Sick Syndrome(ESS)". The physicians should be aware of these changes in order to interpret thyroid function test correctly after the spinal cord injury. We report three cases of ESS after the spinal cord injury. On a routine evaluation, they showed a low serum T3 level, and the T3 level returned to the normal range on a follow up study without any specific treatment.
Euthyroid Sick Syndromes* ; Follow-Up Studies ; Metabolism ; Reference Values ; Spinal Cord Injuries* ; Spinal Cord* ; Thyroid Function Tests ; Thyroid Gland

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

OBJECTIVETo observe dynamic changes of intracellular calcium ([Ca(2+)]i) after spinal cord injury, and to study the relationship between the changes of [Ca(2+)]i and the functional damage of the spinal cord.

METHODSThe rats were subjected to a spinal cord contusion by using a modified Allen's method. The [Ca(2+)]i in the injured segment of the spinal cord was measured by the technique of La(3+) blockage and atomic absorption spectroscopy at 1, 4, 8, 24, 72, and 168 hours after injury. The motor function on the inclined plane was measured at the same time.

RESULTSThe spinal cord [Ca(2+)]i increased significantly (P<0.05 or P<0.01) aft er spinal cord injury. There was a significant correlation (P<0.05) between the changes of [Ca(2+)]i and the motor function.

CONCLUSIONS[Ca(2+)]i overload may play an important role in the pathogenesis of spinal cord injury.

Animals ; Calcium ; metabolism ; Linear Models ; Male ; Rats ; Rats, Wistar ; Spectrophotometry, Atomic ; Spinal Cord Injuries ; metabolism ; physiopathology

OBJECTIVE AND METHODSTo evaluate synaptic changes using synaptophysin immunohistochemstry in rat and mouse, which spinal cords were subjected to graded compression trauma at the level of Th8-9.

RESULTSNormal animals showed numerous fine dots of synaptophysin immunoreactivity in the gray matter. An increase in synaptophysin immunoreactivity was observed in the neuropil and synapses at the surface of motor neurons of the anterior horns in the Th8-9 segments lost immunoreactivity at 4-hour point after trauma. The immunoreactive synapses reappeared around motor neurons at 9-day point. Unexpected accumulation of synaptophysin immunoreactivity occurred in injured axons of the white matter of the compressed spinal cord.

CONCLUSIONSynaptic changes were important components of secondary injuries in spinal cord trauma. Loss of synapses on motor neurons may be one of the factors causing motor dysfunction of hind limbs and formation of new synapses may play an important role in recovery of motor function. Synaptophysin immunohistochemistry is also a good tool for studies of axonal swellings in spinal cord injuries.

Animals ; Axons ; metabolism ; pathology ; Female ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred Strains ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Compression ; Spinal Cord Injuries ; metabolism ; pathology ; Synapses ; metabolism ; pathology ; Synaptophysin ; metabolism