A spinal cord injury is an ailment that can not be treated, but through skillfully planned laboratory research we have been able to accumulate knowledge and expertise that have dramatically improved our understanding of the pathophysiology of SCI. Recent active studies on apoptosis are in now progress, and apoptosis plays a significant role in the long term loss of cells due to damage of these cells. The field is now rapidly advancing due to the development of methodologies such as immunology, molecular biology and genetics. The recent advances in the field of neural regeneration have shed a positive outlook on what once appeared to be an impossible task, that is, to regenerate neurons in the CNS.
Apoptosis ; Molecular Biology ; Neurons ; Regeneration ; Spinal Cord ; Spinal Cord Injuries

Spinal cord injury is a highly disabled neurological disease, and there is still a lack of effective treatments. Studies have proved that olfactory ensheathing cells are one of the ideal seed cells for promoting nerve regeneration after spinal cord injury. Olfactory ensheathing cells can promote axonal germination and elongation through secretion, interaction with astrocytes, regulation of inflammatory reaction, migration characteristics, myelination, anti-oxidation, lipid regulation and other channels. Thus olfactory ensheathing cells play the role of neuroprotection and nerve repair. In recent years, some studies have used bioengineering, tissue engineering, reprogramming and other technologies to enhance the efficacy of olfactoryensheathing cells from different aspects, thereby providing new therapeutic strategies for optimizing the cell therapy of spinal cord injury. This article will summarize the mechanism of olfactory ensheathing cells in repairing spinal cord injury, and review the progress of optimizing strategy of olfactory ensheathing cells in treating spinal cord injury recently, so as to provide new research ideas for the further developing the repair potential of olfactory ensheathing cells and optimize the cell therapy effect of spinal cord injury.
Cell Transplantation ; Humans ; Nerve Regeneration ; Spinal Cord Injuries/therapy*

Spinal cord injury (SCI) has been considered an incurable condition and it often causes devastating sequelae. In terms of the pathophysiology of SCI, reducing secondary damage is the key to its treatment. Various researches and clinical trials have been performed, and some of them showed promising results; however, there is still no gold standard treatment with sufficient evidence. Two therapeutic concepts for SCI are neuroprotective and neuroregenerative strategies. The neuroprotective strategy modulates the pathomechanism of SCI. The purpose of neuroprotective treatment is to minimize secondary damage following direct injury. The aim of neuroregenerative treatment is to enhance the endogenous regeneration process and to alter the intrinsic barrier. With advancement in biotechnology, cell therapy using cell transplantation is currently under investigation. This review discusses the pathophysiology of SCI and introduces the therapeutic candidates that have been developed so far.
Biotechnology ; Cell Transplantation ; Cell- and Tissue-Based Therapy ; Regeneration ; Spinal Cord Injuries* ; Spinal Cord* ; Transplants

STUDY DESIGN: This is a literature review OBJECTIVES: We wanted to provide updated information for spine clinicians on the pathophysiology, medical treatment and the timing of surgical treatment after acute spinal cord injury. SUMMARY OF LITERATURE REVIEW: There are many studies concerned with understanding the mechanisms of injury and improving the neurologic function after acute spinal cord injury. However, methylprednisolone therapy has been used only recently for the treatment of this malady. MATERIALS AND METHODS: We conducted a literature review, with a particular focus on the development of pathophysiology and the emerging pharmacologic treatment of acute spinal cord injury, and on the effectiveness of performing early decompression. RESULTS: After primary mechanical impact, a complex cascade of secondary injury follows during acute spinal cord injury. Neuroprotection and axonal regeneration are the main strategies to treat spinal cord injury. Beyond methylprednisolone, a number of other pharmacological treatments have been studied for the acute treatment of spinal cord injury. Animal studies support early decompression of the injured cord. Although there is no standard regarding the timing of decompression, there are many advantages of performing early decompression in human. CONCLUSION: Although a number of pharmacological therapies seem to have neuroprotective potential, high-dose methyprednisolone therapy is the only clinically approved treatment for acute spinal cord injury. Urgent decompression for acute spinal cord injury remains a reasonable practice option.
Animals ; Axons ; Decompression ; Methylprednisolone ; Regeneration ; Spinal Cord ; Spinal Cord Injuries ; Spine

Possible mechanisms of neurologic recovery in spinal cord injury were postulated by Ditunno Jr. JF in 1987. The first window encompasses recovery from neurapraxia within 6 to 8 weeks. The second window covers the period from 2 to 8 months after the injury. Recovery during this period might be due to peripheral sprouting of intact nerves to denervated muscle and hypertrophy of functioning muscles. The third window of recovery happens usually beyond 8 to 12 months when axonal regeneration may play a role in further increases in strength. On the basis of these possible mechanisms, we measured the neurological and functional recovery rate according to the periods of these possible mechanisms of motor recovery through 12 months following injury in 21 traumatic spinal cord injury patients. The results were as follows: 1) Neurologically, the most rapid recovery was shown within 6 to 8 weeks after injury, during the phase of recovery from neurapraxia. 2) Most of functional recovery occured in the period between 2 month and 8 month of the compensatory phase. 3) Statistically significant correlation between motor and functional recovery was shown among the incomplete spinal cord injury group. These data would be helpful in planning a timely appropriate rehabilitation program by understanding the time-course of neurologic recovery and prognostication of neurologic and functional recovery in the spinal-cord injured.
Axons ; Humans ; Hypertrophy ; Muscles ; Regeneration ; Rehabilitation ; Spinal Cord Injuries* ; Spinal Cord*

The implantation of bioengineered scaffolds into lesion-induced gaps of the spinal cord is a promising strategy for promoting functional tissue repair because it can be combined with other intervention strategies. Our previous investigations showed that functional improvement following the implantation of a longitudinally microstructured collagen scaffold into unilateral mid-cervical spinal cord resection injuries of adult Lewis rats was associated with only poor axon regeneration within the scaffold. In an attempt to improve graft-host integration as well as functional recovery, scaffolds were seeded with highly enriched populations of syngeneic, olfactory bulb-derived ensheathing cells (OECs) prior to implantation into the same lesion model. Regenerating neurofilament-positive axons closely followed the trajectory of the donor OECs, as well as that of the migrating host cells within the scaffold. However, there was only a trend for increased numbers of regenerating axons above that supported by non-seeded scaffolds or in the untreated lesions. Nonetheless, significant functional recovery in skilled forelimb motor function was observed following the implantation of both seeded and non-seeded scaffolds which could not be correlated to the extent of axon regeneration within the scaffold. Mechanisms other than simple bridging of axon regeneration across the lesion must be responsible for the improved motor function.
Adult ; Animals ; Axons* ; Collagen ; Forelimb ; Humans ; Rats ; Regeneration* ; Spinal Cord Injuries* ; Spinal Cord* ; Tissue Donors

Perineuronal nets (PNNs) is a complex network composed of highly condensed extracellular matrix molecules surrounding neurons. It plays an important role in maintaining the performance of neurons and protecting them from harmful substances. However, after spinal cord injury, PNNs forms a physical barrier that surrounds the neuron and limits neuroplasticity, impedes axonal regeneration and myelin formation, and promotes local neuroinflammatory uptake. This paper mainly describes the composition and function of PNNs of neurons and its regulatory effects on axonal regeneration, myelin formation and neuroinflammation after spinal cord injury.
Axons ; Extracellular Matrix ; Humans ; Nerve Regeneration ; Neuronal Plasticity ; Neurons ; Spinal Cord ; Spinal Cord Injuries

PURPOSE: To evaluate the effect of neural stem cells differentiated from a human telencephalon on the neural regeneration in the severed spinal cord. MATERIALS AND METHODS: The 1st surgery involving the insertion of plastic membrane in the transected cord was performed to prevent spontaneous healing of adult female rats (n=20, 171-237 g) with a complete spinal cord transection. The media was inserted only after removing the previously inserted plastic membrane in the control group (n=6). In the experimental group (n=14), media and neural stem cell (1x) were transplanted after removing the membrane, and immunohistochemical staining was performed. The experimental group was perfused transcardially 5 weeks after the 2nd surgery, and the level of neural cell regeneration determined by immunohistochemical staining. In behavioral analysis, the Basso-Beatie-Bresnahan (BBB) scores of the control and experimental group were compared weekly from immediately after the injury until 5 weeks post-injury after the 2nd surgery. RESULTS: Immunohistochemical stain revealed no neural regeneration in the control group. On the other hand, the survival of transplanted human neural stem cells and remarkable neural regeneration (differentiate to neuron and astrocyte) were observed in the experimental group. In the BBB locomotor scale, the experimental group showed significant recovery in terms of control; and the score increased from postoperative 2 weeks to 3 weeks, and reached a plateau from 3 weeks to 5 weeks. CONCLUSION: The effect of neural stem cells differentiated from human telencephalon on cord regeneration does not produce functional recovery in the BBB locomotor scale, but there is slight recovery of the muscle function. The survival of transplanted human neural stem cells and the possibility of differentiation to neurons or astrocytes were observed.
Adult ; Animals ; Astrocytes ; Female ; Hand ; Humans* ; Membranes ; Neural Stem Cells* ; Neurons ; Plastics ; Rats* ; Regeneration ; Spinal Cord Injuries ; Spinal Cord Regeneration* ; Spinal Cord* ; Telencephalon*

Injured primary sensory axons fail to regenerate into the spinal cord, leading to chronic pain and permanent sensory loss. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Why axons stop or turn around at the DREZ has generally been attributed to growth-repellent molecules associated with astrocytes and oligodendrocytes/myelin. The available evidence challenges the contention that these inhibitory molecules are the critical determinant of regeneration failure. Recent imaging studies that directly monitored axons arriving at the DREZ in living animals raise the intriguing possibility that axons stop primarily because they are stabilized by forming presynaptic terminals on non-neuronal cells that are neither astrocytes nor oligodendrocytes. These observations revitalized the idea raised many years ago but virtually forgotten, that axons stop by forming synapses at the DREZ.
Animals ; Astrocytes ; Axons ; Chronic Pain ; Oligodendroglia ; Presynaptic Terminals ; Regeneration ; Spinal Cord ; Spinal Nerve Roots ; Synapses

OBJECTIVE: Previous studies have demonstrated that axon regeneration or remyelination after spinal cord injury occurs when provided with a suitable substratum such as fetal spinal cord (FSC). We carry out this study to determine whether FSC transplants can reduce the glial scar at the interface between host and graft. METHODS: Hemisectioned spinal cord injury was made by aspiration at T3 or T4 spinal cord level in rat. Cell suspension of E-14 FSC was introduced into the injured cavity contaning glial scar tissue. To indentify the transplanted cells from host tissue, FSC cells were labeled with DiI. Rats were sacrificed at 1, 2, 3, and 8 weeks after transplanation and spinal cord was undergone serial sections for immunocytochemistry and histological observation. The observation by electron microscope was carried out too. RESULTS: We could observe that the FSC transplants survived in host spinal cord and generally occupied most of the neuron-depleted area. Examination of serial sections through the graft-host interface which had been immunoreacted for glial fibrillary acidic protein demonstrated that the glial scar was no longer a continuous wall separating the graft and host tissues at eight weeks after injury. We could observe oligodendrocyte and the reformed myelin at the interface by electron microscope. CONCLUSION: The fetal spinal cord transplant can reduce an established glial scar or restrict the reformation of a scar following surgical manipulation, and that the FSC transplant can promote remyelination.
Animals ; Axons ; Cicatrix ; Glial Fibrillary Acidic Protein ; Immunohistochemistry ; Myelin Sheath ; Oligodendroglia ; Rats* ; Regeneration ; Spinal Cord Injuries ; Spinal Cord* ; Transplants