Spinal Cord Injury Characteristics Research Articles

Identification of Cathepsin B as a Therapeutic Target for Ferroptosis of Macrophage after Spinal Cord Injury.

Hemorrhage and immune cell infiltration are the main pathological features of spinal cord injury (SCI). Excessive iron deposition is caused by leaking hemosiderin which may over-activate ferroptosis pathways, resulting in lipid peroxidation and mitochondrial dysfunction in cells. Inhibiting ferroptosis after SCI has been shown to aid functional recovery. However, the essential genes involved in cellular ferroptosis following SCI are still unknown. Here we show that Ctsb is a statistical significance gene by collecting multiple transcriptomic profiles and identifying differentially expressed ferroptosis-related genes, which are abundantly expressed in myeloid cells after SCI and widely distributed at the epicenter of the injury. The expression score of ferroptosis, calculated by ferroptosis driver/suppressor genes, was high in macrophages. Furthermore, we discovered that inhibiting cathepsin B (CTSB), specifically with a small-molecule drug, CA-074-methyl ester (CA-074-me), reduced lipid peroxidation and mitochondrial dysfunction in macrophages. We also found that alternatively activated M2-polarized macrophages are more susceptible to hemin-induced ferroptosis. Consequently, CA-074-me could reduce ferroptosis, induce M2 macrophage polarization, and promote the neurological function recovery of mice after SCI. Our study comprehensively analyzed the ferroptosis after SCI from the perspective of multiple transcriptomes and provided a novel molecular target for SCI treatment.

The Effect of Glycine and N-Acetylcysteine on Oxidative Stress in the Spinal Cord and Skeletal Muscle After Spinal Cord Injury

Oxidative stress is a frequently occurring pathophysiological feature of spinal cord injury (SCI) and can result in secondary injury to the spinal cord and skeletal muscle atrophy. Studies have reported that glycine and N-acetylcysteine (GlyNAC) have anti-aging and anti-oxidative stress properties; however, to date, no study has assessed the effect of GlyNAC in the treatment of SCI. In the present work, we established a rat model of SCI and then administered GlyNAC to the animals by gavage at a dose of 200 mg/kg for four consecutive weeks. The BBB scores of the rats were significantly elevated from the first to the eighth week after GlyNAC intervention, suggesting that GlyNAC promoted the recovery of motor function; it also promoted the significant recovery of body weight of the rats. Meanwhile, the 4-week heat pain results also suggested that GlyNAC intervention could promote the recovery of sensory function in rats to some extent. Additionally, after 4 weeks, the levels of glutathione and superoxide dismutase in spinal cord tissues were significantly elevated, whereas that of malondialdehyde was significantly decreased in GlyNAC-treated animals. The gastrocnemius wet weight ratio and total antioxidant capacity were also significantly increased. After 8 weeks, the malondialdehyde level had decreased significantly in spinal cord tissue, while reactive oxygen species accumulation in skeletal muscle had decreased. These findings suggested that GlyNAC can protect spinal cord tissue, delay skeletal muscle atrophy, and promote functional recovery in rats after SCI.

The Impact of COVID-19 on Epidemiological Features of Spinal Cord Injury in Wuhan, China: A Comparative Study in Different Time Periods.

Background and Objectives: Spinal cord injury (SCI) is a severe affliction that can have a profound impact on a person's ability to move and feel, affecting a significant number of individuals. However, rehabilitation after SCI treatment remains a critical method to improve motor-sensory functions, which improves the patient's quality of life. This study aims to describe the epidemiological profile of SCI during the COVID-19 pandemic ("COVID-19 period") and before and after the COVID-19 pandemic ("non-COVID-19 period") in Wuhan City, Hubei Province, China. Materials and Methods: Medical records of 93 patients diagnosed with SCI admitted to the rehabilitation department of Wuhan Tongji Hospital from January 2019 to May 2023 were retrospectively reviewed. Basic demographics and clinical characteristics such as level of injury, American Spinal Injury Association (ASIA) Impairment Scale, treatment method, and concomitant injuries were analyzed. Results: Forty patients with SCI from the non-COVID-19 period and fifty-three patients from the COVID-19 period were identified. The mean ages were 38.80 ± 17.71 and 44.53 ± 13.27 years, respectively, with a consistent male-to-female ratio of 2:1 across both periods. Notably, falls accounted for the most prevalent mechanism of injury, constituting 50% of cases during the non-COVID-19 period and 37.74% during the COVID-19 period. The most common initial ASIA grade was B in the non-COVID-19 period and grade C in the COVID-19 period. In addition, the final ASIA grade after treatment was grade C in the non-COVID-19 period and grade D in the COVID-19 period. Conclusions: A greater proportion of males suffer from SCI, and the primary causes are falls and traffic accidents. Workers are the most vulnerable group to SCI among all patients. Prevention strategies should be customized based on the unique characteristics of SCI patients. This study highlights the importance of SCI rehabilitation.

Research on Differentiation of Bone Marrow Stromal Cells (BMSCs) Prompted by MicroRNA-124 and Effect on Inflammatory Reaction of Spinal Cord Injury Nerve Cells

The major feature of spinal cord injury (SCI) was the damage of nervous tissue in spinal cord. The damaged spinal cord was difficult to be repaired and regenerated. MicroRNA-124 could play a role in the repairing and recovering the injured tissue. The BMSCs could participate in repairing the damage. However, the regulatory effect of MicroRNA-124 on BMSCs and the inflammatory response of SCI was still not illustrated. These spinal cord nerve cells were assigned into group of mechanical damage, BMSCs and BMSCs with miR-124 overexpression followed by analysis of proliferation of nerve cells by MTT assay, apoptotic activity, expression of miR-124, GFAP and BDNF by Real time PCR, levels of TNF-α and IL-6 by ELISA as well as MDH and SOD activity. miR-124 mimics transfection significantly promoted BMSCs proliferation and increased ALK activity and the expression of GFAP and BDNF. In conclusion, the proliferation and differentiation of BMSCs could be regulated by miR-124. The inflammation and oxidative stress could be restrained so as to prompt the proliferation and repair of SCI cells and restrain apoptosis, indicating that it might be beneficial to recover the SCI.

Spinal Cord Injury in the Mouse Using the Infinite Horizon Spinal Cord Impactor.

Death of central nervous system neurons is a critical feature of spinal cord injury (SCI). The Infinite Horizon spinal cord impactor can be used to create both contusion and compression SCI, with a high degree of reproducibility. The device can also be positioned at different locations along the spinal cord to evaluate how the location of injury may alter neuronal death and functional recovery. A mouse with a successful SCI can experience a period of loss of bladder function, weight loss, and paralysis of the hind limbs, with more severe injuries resulting in further deficits. This chapter describes the surgical protocol along with pre- and postoperative care, as well as mitigation strategies for any setbacks that might occur.

Deubiquitinase USP18 regulates reactive astrogliosis by stabilizing SOX9.

Reactive astrogliosis is a pathological feature of spinal cord injury (SCI). The ubiquitin-proteasome system plays a crucial role in maintaining protein homeostasis and has been widely studied in neuroscience. Little, however, is known about the underlying function of deubiquitinating enzymes in reactive astrogliosis following SCI. Here, we found that ubiquitin-specific protease 18 (USP18) was significantly upregulated in astrocytes following scratch injury, and in the injured spinal cord in mice. Knockdown of USP18 in vitro and conditional knockout of USP18 in astrocytes (USP18 CKO) in vivo significantly attenuated reactive astrogliosis. In mice, this led to widespread inflammation and poor functional recovery following SCI. In contrast, overexpression of USP18 in mice injected with adeno-associated virus (AAV)-USP18 had beneficial effects following SCI. We showed that USP18 binds, deubiquitinates, and thus, stabilizes SRY-box transcription factor 9 (SOX9), thereby regulating reactive astrogliosis. We also showed that the Hedgehog (Hh) signaling pathway induces expression of USP18 through Gli2-mediated transcriptional activation after SCI. Administration of the Hh pathway activator SAG significantly increased reactive astrogliosis, reduced lesion area and promoted functional recovery in mice following SCI. Our results demonstrate that USP18 positively regulates reactive astrogliosis by stabilizing SOX9 and identify USP18 as a promising target for the treatment of SCI.

The clinical and subclinical features of spinal cord injury on magnetic resonance imaging of patients with N2O intoxication.

Nitrous oxide (N2O) is a weak anesthetic gas that was first used in 1844 in the field of dental anesthesia. However, currently, N2O is being abused for entertainment purposes in the form of N2O-filled balloons, called funky balls, which can cause many adverse effects, especially nervous system injury. This study aimed to investigate the detailed clinical and subclinical features associated with N2O intoxication. We retrospectively reviewed 47 patients diagnosed with N2O intoxication, from May 2018 to July 2019, and collected demographic data, clinical and laboratory tests, and spinal cord magnetic resonance imaging (MRI) findings. The mean time of funky ball use was 8.8 months, with a mean use of 36.3 balls per day. All patients presented with superficial sensory disorders. Reductions in muscle strength, decreased vibration sensation, and decreased or lost tendon reflexes were the most common clinical signs of N2O intoxication. Romberg sign and Lhermitte sign were observed in 39 patients (83%) and 21 patients (44.7%), respectively. Spinal cord lesions on MRI were observed in 32 patients (68.1%), which mostly presented with an inverted V sign. The total duration of N2O use, the number of days of using N2O per week, and the presence of Lhermitte sign (P<0.05) were significantly different between patients with and without spinal cord lesions on MRI. Serum levels of homocysteine and vitamin B12 were significantly different between the time of admission and discharge (P<0.05). Our study indicated that the days of using N2O per week was significantly associated with Spinal Cord Injuries (SCI) on MRI. According to the Receiver Operating Characteristic (ROC) curve analysis, a cutoff days of using per week value of 2.5 days could predict SCI with a sensitivity of 81.3%, a specificity of 73.3%, and an area under the ROC curve (AUC) of 0.813. Changes in the serum levels of homocysteine and vitamin B12 were effective markers for the evaluation of treatment response.

Traumatic spinal cord injuries in Saint Petersburg: clinical and neurological features and mortality rate

A retrospective cohort descriptive study based on archived patient's charts was performed to research the clinical and neurological features of patients with traumatic spinal cord injuries and analyze predictors of hospital mortality rate. We analyzed 311 cases of acute spinal cord injury for 2012–2016. The relationship of gender and age characteristics, and clinical/neurological features of spinal cord injuries is described. The mortality rate dependence on the level and severity of spinal cord injuries was revealed. Risk factors such as concomitant traumatic brain injury and alcohol consumption before injury were identified.

Innovative mouse model mimicking human-like features of spinal cord injury: efficacy of Docosahexaenoic acid on acute and chronic phases

Traumatic spinal cord injury has dramatic consequences and a huge social impact. We propose a new mouse model of spinal trauma that induces a complete paralysis of hindlimbs, still observable 30 days after injury. The contusion, performed without laminectomy and deriving from the pressure exerted directly on the bone, mimics more closely many features of spinal injury in humans. Spinal cord was injured at thoracic level 10 (T10) in adult anesthetized female CD1 mice, mounted on stereotaxic apparatus and connected to a precision impactor device. Following severe injury, we evaluated motor and sensory functions, and histological/morphological features of spinal tissue at different time points. Moreover, we studied the effects of early and subchronic administration of Docosahexaenoic acid, investigating functional responses, structural changes proximal and distal to the lesion in primary and secondary injury phases, proteome modulation in injured spinal cord. Docosahexaenoic acid was able i) to restore behavioural responses and ii) to induce pro-regenerative effects and neuroprotective action against demyelination, apoptosis and neuroinflammation. Considering the urgent health challenge represented by spinal injury, this new and reliable mouse model together with the positive effects of docosahexaenoic acid provide important translational implications for promising therapeutic approaches for spinal cord injuries.

Overexpression of lncRNA TCTN2 protects neurons from apoptosis by enhancing cell autophagy in spinal cord injury.

Neuronal apoptosis is the main pathological feature of spinal cord injury (SCI), while autophagy contributes to ameliorating neuronal damage via inhibition of apoptosis. Here, we investigated the role of tectonic family member 2 (TCTN2) long non‐coding RNA on apoptosis and autophagy in SCI. TCTN2 was down‐regulated in the spinal cord tissues of a rat model of SCI and in oxygen–glucose deprivation‐induced hypoxic SY‐SH‐5Y cells, while microRNA‐216b (miR‐216b) was up‐regulated. Overexpression of TCTN2 reduced neuron apoptosis by inducing autophagy, and TCTN2 was observed to negatively regulate miR‐216b. Furthermore, TCTN2 promoted autophagy to repress apoptosis through the miR‐216b–Beclin‐1 pathway, and overexpression of TCTN2 improved neurological function in the SCI rat model. In summary, our data suggest that TCTN2 enhances autophagy by targeting the miR‐216b–Beclin‐1 pathway, thereby ameliorating neuronal apoptosis and relieving spinal cord injury.

Decrease in Cavity Size and Oligodendrocyte Cell Death Using Neurosphere-Derived Oligodendrocyte-Like Cells in Spinal Cord Contusion Model

Background:Oligodendrocyte cell death is among the important features of spinal cord injury, which appears within 15 min and occurs intensely for 4 h after injury, in the rat spinal contusion model. Accordingly, the number of oligodendrocytes progressively reduced within 24 h after injury. Administration of oligodendrocyte-like cells (OLCs) into the lesion area is one of the approaches to counterbalance this condition.Methods:Bone marrow stromal cells were transdifferentiated into neurospheres and then into neural stem cells and later were differentiated into OLCs using triiodothyronine and transplanted into the spinal cord contusion rats. The post-injury functional recovery was explored and compared with the control group using Basso-Beattie-Bresnahan and narrow beam behavioral tests. At the end of 12th week, spinal cord segments T12-L1 were histomorphologically studied by immunohistochemistry.Results:Motor improvement was more obvious during 2nd to 4th weeks and got less prominent during 4th to 12th weeks. Histomorphometric findings indicated that cavity formation decreased in epicenter of transplantation area in experimental groups in comparison with the control groups.Conclusion:The findings obtained in the present study showed that OLC therapy is a potential approach in the treatment of spinal cord traumatic injuries.

Descriptive study of earthquake-related spinal cord injury in Nepal

Descriptive study. To describe the epidemiological features of spinal cord injury (SCI) following the 2015 earthquakes in Nepal. Spinal Injury Rehabilitation Centre, Kavre, Nepal. Data were collected from the medical records of all earthquake-related patients seen from 25 April 2015 through to 16 June 2016. Data collected included patient demographics, mechanism of injury, initial medical treatment, neurological assessment, complications, neurological/functional outcomes and length of stay. Data from 117 earthquake-related SCI patients were evaluated, with a female-to-male ratio of 1.3:1. In total, 108 patients (92%) sustained vertebral fracture and/or dislocation. Seventy-seven patients had undergone surgical fixation. The majority of patients (81%) presented with paraplegia, of whom most (60%) were incomplete. Thirty-eight (33%) patients had documented pressure ulcers upon admission; six (5%) patients developed new pressure ulcers during their rehabilitation stay. Urinary tract infection was seen in 34 (29%) patients. Seven (6%) patients were diagnosed with deep vein thrombosis. One patient developed clinically significant heterotopic ossification. Significant improvements were seen in patients' functional outcomes before discharge. Two deaths occurred in this patient population. The Nepal earthquakes resulted in a significant number of SCIs, the majority occurring in women. Incomplete paraplegia was the most common presentation. Pressure ulcer, the most frequent complication, primarily occurred before rehabilitation admission. Continued efforts focused on comprehensive planning, and preparedness for SCI-specific interdisciplinary care following earthquakes, particularly in resource-limited settings, is critical to ensuring survival, preventing complications and optimizing functional outcomes in this patient population.

Contemporary Trends in the Epidemiology of Traumatic Spinal Cord Injury: Changes in Age and Etiology

Background: Epidemiological features of spinal cord injury (SCI) have been changing over the last decades. We evaluated the contemporary trends in the epidemiology of traumatic SCI patients from a rehabilitation center. Methods: In a cross-sectional study, a consecutive series of 348 patients with traumatic SCI were evaluated. Variables were collected through an epidemiological form, which included gender, age at injury, duration and cause of SCI. We investigated SCI epidemiological trends over time including the association between gender and age at injury with SCI features such as etiology, injury severity and level. Results: The mean age at SCI has increased from 26.0 ± 11.8 in patients with SCI before 2003 to 37.9 ± 15.7 in those with SCI after 2009 (p < 0.001). Gunshot wounds were the main cause of injury in patients with SCI before 2003, dropping from 40.6 to 16.9% after 2009 and being surpassed by road traffic injuries (38.6%) and falls (31.4%) after 2009 (p < 0.001). Gender, SCI severity and level have not changed significantly over the time. Conclusions: There was a major increase in the average age of patients as well as changes in the etiology of SCI over the past fifteen years, including a significant decrease in gunshot wounds and an increase in the frequency of road traffic injuries and falls. These changes and accompanying risk factors must be taken into consideration when planning measures to prevent SCI.

The development of a rat in vitro model of spinal cord injury demonstrating the additive effects of rho and ROCK inhibitors on neurite outgrowth and myelination

It is currently thought that treatment for spinal cord injury (SCI) will involve a combined pharmacological and biological approach; however, testing their efficacy in animal models of SCI is time-consuming and requires large animal cohorts. For this reason we have modified our myelinating cultures as an in vitro model of SCI and studied its potential as a prescreen for combined therapeutics. This culture comprises dissociated rat embryonic spinal cord cells plated onto a monolayer of astrocytes, which form myelinated axons interspaced with nodes of Ranvier. After cutting the culture, an initial cell-free area appears persistently devoid of neurites, accompanied over time by many features of SCI, including demyelination and reduced neurite density adjacent to the lesion, and infiltration of microglia and reactive astrocytes into the lesioned area. We tested a range of concentrations of the Rho inhibitor C3 transferase (C3) and ROCK inhibitor Y27632 that have been shown to promote SCI repair in vivo. C3 promoted neurite extension into the lesion and enhanced neurite density in surrounding areas but failed to induce remyelination. In contrast, while Y27632 did not induce significant neurite outgrowth, myelination adjacent to the lesion was dramatically enhanced. The effects of the inhibitors were concentration-dependent. Combined treatment with C3 and Y27632 had additive affects with an enhancement of neurite outgrowth and increased myelination adjacent to the lesion, demonstrating neither conflicting nor synergistic effects when coadministered. Overall, these results demonstrate that this culture serves as a useful tool to study combined strategies that promote CNS repair.

Melatonin prevents muscle atrophy and the alteration of myosin heavy chain in spinal cord injured rats

The purpose of this study was to confirm the behavioral features of spinal cord injury (SCI) and to investigate the effects of melatonin on muscle atrophy and shifts in myosin heavy chain (MHC) in an SCI model. SCIs were surgically induced in eight‐week‐old male Sprague‐Dawley (SD) rats that had been randomly divided into three groups: Control, SCI (n=13), and melatonin‐treated after SCI (SCI+MT, n=13). Melatonin (10 mg/kg body weight) was injected subcutaneously twice a day (07:00 and 19:00) for four weeks, after which the body weight and motor function of the rats were evaluated. The expression of muscle atrophy‐related genes in hindlimb muscles, including MAFbx and MuRF1, and MHC, were also analyzed. The body weight and motor functions of the rats were decreased at the acute phase after SCI. The gene expression of MAFbx and MuRF1 were increased in the hindlimb muscles (p&lt;.05), indicating SCI‐induced muscle atrophy. Melatonin contributed to motor recovery, decreased MAFbx and MuRF1 gene expression, and altered MHC expression in the hindlimb muscles (p&lt;.05). Thus, melatonin may promote functional recovery, prevent muscle atrophy, and alter MHC expression after SCI.Funding: BioGreen21 Program (Code No. 20070401‐034‐006‐009‐02‐00), Rural Development Administration, Korea

The Extent of Myelin Pathology Differs following Contusion and Transection Spinal Cord Injury

Demyelination is a prominent feature of spinal cord injury (SCI) and is followed by incomplete remyelination, which may contribute to physiological impairment. Demyelination has been documented in several species including humans, but the extent of demyelination and its functional consequence remain unknown. In this report, we document and compare the extent of tissue pathology, white matter apoptosis, demyelination, and remyelination 2 months following injury in rat contusion and transection models of SCI. Moreover, we document and compare the macrophage response 3 and 14 days post contusion and transection SCI. Contusion injury resulted in widespread tissue pathology, white matter apoptosis, demyelination, incomplete remyelination, and robust macrophage response extending several millimeters cranial and caudal to the epicenter of injury. In contrast, transection injury resulted in focal tissue pathology with white matter apoptosis, demyelination, incomplete remyelination, and robust macrophage response at the epicenter of injury, and little pathologic features at a distance from the epicenter of injury, as indicated by the lack of apoptosis and demyelination. These data indicate for the first time that myelin pathology differs substantially following contusion and transection SCI.

Survey of Spinal Cord Injuries Due to Diving Accidents in Taiwan

Objective: To examine the clinical characteristics of diving-related spinal cord injuries (SCI) in Taiwan. Methods: This study is a retrospective review of all hospitalized patients with spinal cord injuries due to diving accidents in three rehabilitation centers between January 1982 and July 2002. Demographic data and clinical features were presented and analyzed. Results: A total of 1216 spinal cord injuries were reviewed, and 16 cases (1.3%) met the inclusion criteria. Their mean age at the time of injury was 26.8 years and 15 (94.0%) of the cases were male. All of the injuries resulted in tetraplegia and 11 (69.0%) were neurologically complete. The most commonly neurological level was C5. The most common vertebral injury level was C5 (50.0%), followed by C4 and C6. All of the injuries occurred during summer and 63.0% occurred in the open water. Associated injuries were rare. A total of 75.0% of the patients underwent surgical treatment and neurological recovery was observed in 37.5% of these cases, of which most were incomplete injuries. Discussion and Conclusions: The proportion of diving-related spinal cord injuries in our study was lower than most of the previous reports. A higher percentage of traffic accidents and accidental falls, and a reduced popularity of water sports are possible reasons. We observed some typical features of SCI due to diving accidents in our study. Most of the diving accidents occurred among young males, and resulted in mid-cervical injuries with complete tetraplegia. Our results show that injury-preventing strategies need to be emphasized.

Spinal cord injuries due to diving accidents

Retrospective study and data analysis. To investigate and analyse the main features of spinal cord injuries due to diving accidents accepted in our Centre from June 1978 to December 2002. Regional Spinal Unit of Florence, Italy. Diving accidents mostly occur in a young and healthy population and most of the patients develop tetraplegia with a severe lifelong disability. From 1978 to 2002, 65 patients with spinal injuries due to diving accidents were admitted to the Regional Spinal Unit of Florence. A retrospective study was conducted by analysing data stored in our local computerized database. We considered the vertebral injury, ASIA-ISCOS neurological classification on admission and discharge, gender, age at the time of injury, month of injury, treatment of vertebral lesion, length of stay in the Spinal Unit, neurological outcome, and complications. Data were analysed statistically by using the Fisher's exact test and logistic regression. In all, 62/65 patients were males (95%). Mean age at injury time: 22 years. On admission, 35/65 were neurologically complete ASIA A (54%), while 16 were classified ASIA B, 7 ASIA C and 7 ASIA D, according to the ASIA-ISCOS neurological standard of classification. C6 was the most common neurological motor level (40%) and C5 the most common vertebral injury level. In all, 36/65 (55%) patients underwent surgical treatment. Mean hospitalization time was 5 months. No neurological deterioration was recorded. In all, 20/65 (31%) patients improved neurologically and 16/20 (80%) of those had received surgical treatment. In all, 15/65 (23%) patients had complications and one patient died during the hospitalization period. Patients whose vertebral lesions were surgically treated had a better neurological outcome than conservatively treated ones. Teardrop fractures showed worse neurological outcome as compared with burst fractures. Neurological improvement was more present in initially incomplete lesions. Treatment with high dose methylprednisolone during the first 8 h after trauma seemed to influence the neurological outcome positively. Age was also an important factor in influencing the neurological outcome.

Axonal Regeneration and Lack of Astrocytic Gliosis in EphA4-Deficient Mice

Spinal cord injury usually results in permanent paralysis because of lack of regrowth of damaged neurons. Here we demonstrate that adult mice lacking EphA4 (-/-), a molecule essential for correct guidance of spinal cord axons during development, exhibit axonal regeneration and functional recovery after spinal cord hemisection. Anterograde and retrograde tracing showed that axons from multiple pathways, including corticospinal and rubrospinal tracts, crossed the lesion site. EphA4-/- mice recovered stride length, the ability to walk on and climb a grid, and the ability to grasp with the affected hindpaw within 1-3 months of injury. EphA4 expression was upregulated on astrocytes at the lesion site in wild-type mice, whereas astrocytic gliosis and the glial scar were greatly reduced in lesioned EphA4-/- spinal cords. EphA4-/- astrocytes failed to respond to the inflammatory cytokines, interferon-gamma or leukemia inhibitory factor, in vitro. Neurons grown on wild-type astrocytes extended shorter neurites than on EphA4-/- astrocytes, but longer neurites when the astrocyte EphA4 was blocked by monomeric EphrinA5-Fc. Thus, EphA4 regulates two important features of spinal cord injury, axonal inhibition, and astrocytic gliosis.

Effects of Different Anesthetics on the Paired-Pulse Depression of the H Reflex in Adult Rat

Hyperreflexia is a common feature of spinal cord injury (SCI), and changes in reflex excitability have been reported to be useful in assessing treatments in animal models of cord damage. However, spinal reflexes are known to be dependent on anesthetic level. As a preliminary to its use in SCI, the excitability of the Hoffman reflex (H reflex) has been assessed under several commonly used anesthetics. The H reflex was recorded in the distal foot muscles (dorsal interossei) of adult rats, while the lateral plantar nerve was stimulated. Five different anesthetics were used: ketamine, halothane, Nembutal, Etomidate, and Saffan. Recording and stimulating electrodes were inserted directly through the skin to minimize the surgical procedure for each experiment, allowing repeated recording to be made in the same animal on a weekly basis. Suppression of the H reflex was tested using twin-pulse stimulation. Halothane and ketamine produced suppression of the H response when interpulse intervals were shortened to less than 1 s. The H-reflex suppression profiles recorded under Etomidate, Saffan, and Nembutal anesthesia were less sensitive to the stimulation rate, with little reduction until intervals were 200 ms or less. The suppression profiles of halothane and ketamine resemble that seen in unanesthetized humans, whereas that under the other anesthetics tried here resembles that observed in spinal-cord-injured animals. The results suggest a preferential action of some anesthetics on descending pathways involved in reflex modulation and the importance of assessing reflex excitability under anesthetics such as ketamine or halothane.