成年大鼠脊髓全横断损伤后酪氨酸激酶受体C在脊髓和大脑皮层的表达

目的 研究神经营养因子3(neurotrophin-3,NT-3)的受体-酪氨酸激酶受体C(tyrosine kinase receptor C,TrkC)在脊髓损伤(spinal cord injury,SCI)后神经重塑中的作用.方法 研究脊髓全横断损伤大鼠手术后第1、3、7和14 d时,低位胸髓节段和大脑中央前回...     

Temporal changes in the expression of some neurotrophins in spinal cord transected adult rats

Functional recovery of neurons in the spinal cord after physical injury is essentially abortive in clinical cases. As neurotrophins had been reported to be responsible, at least partially, for the lesion-induced recovery of spinal cord, it is not surprising that they have become the focus of numerous studies. Studies on endogenous neurotrophins, especially the three more important ones, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in injured spinal cord might provide some important clues in clinical treatment. Here we investigate the immunohistological expression of the above three factors at lower thoracic levels of the spinal cord as well as changes in the motor functions of the adult rat hindlimbs after cord transection. The injured rats were allowed to survive 3, 7, 14 and 21 days post operation (dpo). Flaccid paralysis was seen at 3 dpo following cord transection, however, hindlimb function showed partial recovery from 7 dpo to 21 dpo. The numbers of NGF, BDNF and NT-3 immunopositive neurons and their optical densities all increased in the lesion-induced cord. The immuno-expression of NGF and BDNF peaked at 7 dpo, while that of NT-3 peaked at 7 dpo and remained so at least up to 14 dpo. These results suggested that neurotrophins might play essential roles in functional recovery of after spinal cord injury, but the time points for the expression of the three factors differed somewhat.     

Spinal motoneuron dendritic alteration after spinal cord hemisection in the rat

Alteration of spinal motoneurons can be induced by axotomy, deafferentation, or deafferentation of spinal interneurons. In our experiment, dendritic profiles of rat lamina IX motoneurons were studied 1.5 to 2.5 mm rostral to a T2, T3 (interface) hemisection [six per group of normal, 7-, 14-, 30-, 60-, and 90-day postoperative (DPO) animals]. The spinal cord was impregnated using the Golgi technique and individual dendritic segments measured from coded slides, the data were computerized, and the length, number of segments, and dendritic profile were reconstructed. These data were heteroscedastic (α < 0.005) making them inappropriate for ANOVA. However, the data did show two size classes of motoneurons at 14, 30, 60, and 90 DPO. At 7 DPO, there was a reduced dendritic field. At 14 to 60 DPO, there were gigantic motoneurons that were many times larger than normal or other neurons in these operated groups. At 90 DPO a large motoneuron was present. These data show that individual motoneurons have different regenerative dendritic responses after spinal injury.     

FK 506 reduces tissue damage and prevents functional deficit after spinal cord injury in the rat

We examined the efficacy of FK 506 in reducing tissue damage after spinal cord injury in comparison to methylprednisolone (MP) treatment. Rats were subjected to a photochemical injury (T8) and were given a bolus of MP (30 mg/kg), FK 506 (2 mg/kg), or saline. An additional group received an initial bolus of FK 506 (2 mg/kg) followed by daily injections (0.2 mg/kg intraperitoneally). Functional recovery was evaluated using open-field walking, inclined plane tests, motor evoked potentials (MEPs), and the H-reflex response during 14 days postoperation (dpo). Tissue sparing and glial fibrillary acidic protein (GFAP), biotinylated tomato lectin LEC, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin 1 beta (IL-1 beta) immunoreactivity were quantified in the injured spinal cord. FK 506-treated animals demonstrated significantly better neurologic outcome, higher MEP amplitudes, and lower H-wave amplitude compared to that of saline-treated rats. In contrast, administration of MP did not result in significant differences with respect to the saline-treated group. Histologic examination revealed that tissue sparing was largest in FK 506-treated compared to saline and MP-treated animals. GFAP and COX-2 reactivity was decreased in animals treated with FK 506 compared to that in animals given MP or saline, whereas IL-1 beta expression was similarly reduced in both FK 506- and MP-treated groups. Microglia/macrophage response was reduced in FK 506 and MP-injected animals at 3 dpo, but only in MP-treated animals at 7 dpo with respect to saline-injected rats. Repeated administrations of FK 506 improved functional and histologic results to a greater degree than did a single bolus of FK 506. The results indicate that FK 506 administration protects the damaged spinal cord and should be considered as potential therapy for treating spinal cord injuries.     

Cervical motoneuron topography reflects the proximodistal organization of muscles and movements of the rat forelimb: a retrograde carbocyanine dye analysis

Behavioral evidence reveals that the laboratory rat and other rodent species display skilled paw and digit use in handling food during eating and skilled limb use in reaching for food in formal laboratory skilled reaching tests that is comparable to that described in carnivores and primates. Because less is known about the central control of skilled movements in rodents than in carnivores or primates, the purpose of the current study was to examine the relation between the rat's spinal motoneurons and the individual forelimb muscles that they innervate. In two experiments, 14 forelimb muscles (in the shoulder and the upper and lower arm segments) were injected with carbocyanine dye tracers. The topography of spinal motoneurons was reconstructed by using fluorescence microscopy. Motor neurons were found to be organized in columns throughout the length of the cervical and upper thoracic area, with 1) extensor motoneurons located more laterally than flexor motoneurons, 2) rostral motoneurons innervating more proximal muscles than caudal motoneurons, and 3) more dorsally located motoneurons innervating more distal muscles. These results reveal that the topography of rodent cervical spinal cord motoneurons is very similar to that of carnivores and of primates, which also are characterized by well-developed, skilled movements. In addition, the proximal-distal organization of motoneuron columns parallels the proximal-to-distal pattern of forelimb movement used by the rat when reaching. The data from this study enable the development of predictions about the specific movements that would be compromised by experimental transections or other injuries at different levels of the spinal cord in rat models of spinal injury.     

Levels of brain-derived neurotrophic factor and neurotrophin-4 in lumbar motoneurons after low-thoracic spinal cord hemisection

Neuroplasticity represents a common phenomenon after spinal cord (SC) injury or deafferentation that compensates for the loss of modulatory inputs to the cord. Neurotrophins play a crucial role in cell survival and anatomical reorganization of damaged spinal cord, and are known to exert an activity-dependent modulation of neuroplasticity. Little is known about their role in the earliest plastic events, probably involving synaptic plasticity, which are responsible for the rapid recovery of hindlimb motility after hemisection, in the rat. In order to gain further insight, we evaluated the changes in BDNF and NT-4 expression by lumbar motoneurons after low-thoracic spinal cord hemisection. Early after lesion (30 min), the immunostaining density within lumbar motoneurons decreased markedly on both ipsilateral and contralateral sides of the spinal cord. This reduction was statistically significant and was then followed by a significant recovery along the experimental period (14 days), during which a substantial recovery of hindlimb motility was observed. Our data indicate that BDNF and NT-4 expression could be modulated by activity of spinal circuitry and further support putative involvement of the endogenous neurotrophins in mechanisms of spinal neuroplasticity.     

Effects of electro-acupuncture on CNTF expression in spared dorsal root ganglion and the associated spinal lamina II and nucleus dorsalis following adjacent dorsal root ganglionectomies in cats

It is well known that plasticity occurs in deafferented spinal cord, and that electro-acupuncture (EA) could promote functional restoration. The underlying mechanism is, however, unknown. Ciliary neurotrophic factor (CNTF) plays a crucial role in neurite outgrowth and neuronal survival both in vivo and in vitro, and its expression might explain some of the mechanism. In this study, we investigated the effects of EA on CNTF expression in the spared L(6) dorsal root ganglion (DRG), and spinal lamina II at spinal segments L(3) and L(6) as well as nucleus dorsalis (ND) of L(3) spinal segment following removal of L(1)-L(5) and L(7)-S(2) (DRG) in the cat. After ganglionectomies, the total and small-to-medium-sized numbers of immunoreactive neurons decreased at 3 dpo, and returned to the sham-operated level as early as 7 dpo. After EA, immunoreactive neurons in L(6) DRG noticeably increased at 7 dpo, compared with the non-acupunctured group. Notable increase in the large neurons was seen at 14 dpo, while their numbers in L(3) and L(6) spinal cord segments significantly declined at 3 dpo. Those in L(3) segment did not reach the sham-operated level until 14 dpo, but their numbers in L(6) segment returned to the sham-operated level as early as 7 dpo. CNTF immunopositive neurons in the ND of L(3) segment returned to the sham-operated level at 14 dpo. After EA, their number significantly increased as early as 7 dpo in lamina II of L(6) segment, and as late as 14 dpo in ND of L(3) segment. Western blot analysis showed CNTF changes corresponding to those shown in immunohistochemical staining. It is concluded that CNTF expression was involved in the EA promoted plastic changes in L(6) DRG and the associated deafferented spinal lamina and ND.     

betaII-tubulin and GAP 43 mRNA expression in chronically injured neurons of the red nucleus after a second spinal cord injury

Regeneration by chronically injured supraspinal neurons is enhanced by treatment of a spinal cord lesion site with a variety of neurotrophic and growth factors. The removal of scar tissue, with subsequent reinjury of the spinal cord, is necessary for injured axons to access tissue transplants placed into the lesion to support axon regrowth. The present study examined chronically injured and reinjured rubrospinal tract (RST) neurons to determine if changes in gene expression could explain the failure of these neurons to regenerate without exogenous trophic factor support. Adult female rats were subjected to a right full hemisection lesion via aspiration of the cervical level 3 spinal cord. Using radioactive cDNA probes and in situ hybridization, RST neurons in the contralateral red nucleus were examined for changes in mRNA levels of betaII-tubulin and GAP 43 in an acute injury period (6 h-3 days), a chronic injury period (28 days after spinal cord injury (SCI)) and following a second lesion of the chronic injury site (6 h-7 days). Based upon the analysis of gene expression in single cells, GAP-43 mRNA levels were increased as early as 1 day following the initial SCI, but were no different than uninjured control levels at 28 days postoperative (dpo). The response to relesion was more rapid and higher than that detected after the initial injury with a significant increase in GAP 43 mRNA at 6 h that was maintained for at least 7 days. betaII-tubulin mRNA levels remained unchanged until 3 days after an acute injury followed by a decrease in expression to 30% below uninjured control values at 28 dpo. The expression of betaII-tubulin mRNA was significantly higher within 6 h after a second injury, where it remained stable for 5 days before a second increase occurred at 7 days after reinjury of the spinal cord. Thus, neurons in a chronic injury state retain the ability to respond to a traumatic injury and, in fact, neurons subjected to a second injury exhibit a significantly heightened expression of regeneration-associated genes.     

Cortical and subcortical compensatory mechanisms after spinal cord injury in monkeys

This is a review of our investigations into the neuronal mechanisms of functional recovery after spinal cord injury (SCI) in a non-human primate model. In primates, the lateral corticospinal tract (l-CST) makes monosynaptic connections with spinal motoneurons. The existence of direct cortico-motoneuronal (CM) connections has been thought to be the basis of dexterous digit movements, such as precision gripping. However, recent studies have shown that after lesion of the direct CM connections, by a l-CST lesion at the C4/C5 level, precision gripping is initially impaired, but shows remarkable recovery with training within several weeks. Plastic changes of the neural circuits underlying the recovery occur at various levels of the central nervous system. In the subcortical networks, intracellular recordings from the motoneurons in anesthetized animals demonstrated that transmission through the disynaptic pathways from the CST was enhanced, presumably mediated by the propriospinal neurons in the mid-cervical segments. The γ-band musculo-muscular coherence (MMC), with a peak frequency around 30 Hz, appeared over a wide range of forelimb muscles and was strengthened in parallel to the recovery of the precision grip. Appearance of the γ-band MMC also paralleled the change in the activation pattern of forelimb muscles; muscles which were antagonists before the lesion showed co-activation after recovery. Such γ-band MMC is thought to originate in the subcortical network, presumably in the brainstem or spinal cord. In the cortical networks, a combination of positron emission tomography and reversible inactivation techniques has shown that the bilateral primary motor cortex (M1) and ventral premotor cortex (PMv) have different contributions to functional recovery depending on the recovery stage; the bilateral M1 plays a major role in early stage recovery (<1 month), whereas the contralateral M1 and bilateral PMv are the prominent contributors to the later stages (3-4 months). Such changes in cortical activity in M1 and PMv have been shown to accompany changes in the expressions of plasticity-related genes, such as GAP-43. Changes in the dynamic properties of neural circuits, both at the cortical and subcortical levels, are time-dependent. Multidisciplinary studies to clarify how the changes in the dynamic properties of individual components of the large-scaled networks are coordinated during recovery will help to develop effective therapeutic strategies to recovery from SCI.     

Establishment of pure neuronal cultures from fetal rat spinal cord and proliferation of the neuronal precursor cells in the presence of fibroblast growth factor.

A primary culture system of nearly pure neuronal cells from 14-day-old fetal rat spinal cord has been developed by combining a preplating step, the use of a chemically defined serum-free medium, and borated polylysine-coated dishes that prevented the formation of cell aggregates. About 98% of the cells were found to be immunostained with neuron-specific enolase antibodies, confirming their neuronal nature. The cultures are composed essentially of a population of non-motoneurons and contain few motoneurons, characterized by their large size and multipolar aspect, the presence of acetylcholinesterase (AChE), and the intense immunoreaction for growth-associated protein GAP-43. Neuronal precursor cells are also present in these cultures and proliferate during the first 3 days. The addition of bovine brain basic fibroblast growth factor (bFGF) stimulates their proliferation over a period of 2 days, as determined by measurement of [125I]iododeoxyuridine incorporation and by immunocytochemical reaction after bromodeoxyuridine incorporation into nuclei. The proliferating cells were characterized as neurons by immunostaining against neuron-specific enolase. Recombinant human bFGF and bovine brain acidic FGF (aFGF) exerted similar effects. Other growth factors, including epidermal growth factor (EGF), transforming growth factor beta 1 (TGF-beta 1), and thrombin, were without effect on the proliferative activity of these neuronal cells. bFGF has no effect on the survival of motoneurons and on the fiber outgrowth of the whole neuronal population. However, bFGF affects the development of bipolar AChE-positive neurons, probably belonging to the non-motoneuron population. The data indicate that bFGF and aFGF are mitogens for neuroblasts from rat spinal cord in culture and that bFGF influences the development of a subpopulation of spinal neurons that are AChE-positive.     

Regional variations in the extent and timing of motoneuron cell death in the lumbosacral spinal cord of the chick embryo

We have examined the distribution of motoneurons in different segments of the chick lumbosacral spinal cord before and after the period of motoneuron cell death. The extent of cell death was found to be greatest at the boundaries of the lumbosacral cord where over 60% of the motoneurons died and least in the central region where only 30% died. After cell death at stage 40 the number of motoneurons in each segment was linearly correlated with segment length, suggesting that growth of the segment and motoneuron numbers may be regulated by a common factor. The time of completion of motoneuron cell death exhibited a rostrocaudal gradient along the lumbar cord. Cell death was complete in the anterior segments by stage 35 but not until stage 38 in the caudal 4 segments. The regional variations in the extent and timing of motoneuron cell death suggest that the relative importance of the factors mediating cell death vary in different regions of the lumbar cord.     

Jisuikang,a Chinese herbal formula,increases neurotrophic factor expression and promotes the recovery of neurological function after spinal cord injur y

The Chinese medicine compound, Jisuikang, can promote recovery of neurological function by inhibiting lipid peroxidation, scavenging oxygen free radicals, and effectively improving the local microenvironment after spinal cord injury. However, the mechanism remains unclear. Thus, we established a rat model of acute spinal cord injury using a modified version of Allen's method. Jisuikang(50, 25, and 12.5 g/kg/d) and prednisolone were administered 30 minutes after anesthesia. Basso, Beattie, and Bresnahan locomotor scale scores and the oblique board test showed improved motor function recovery in the prednisone group and moderate-dose Jisuikang group compared with the other groups at 3–7 days post-injury. The rats in the moderate-dose Jisuikang group recovered best at 14 days post-injury. Hematoxylin-eosin staining and transmission electron microscopy showed that the survival rate of neurons in treatment groups increased after 3–7 days of administration. Further, the structure of neurons and glial cells was more distinct, especially in prednisolone and moderate-dose Jisuikang groups. Western blot assay and immunohistochemistry showed that expression of brain-derived neurotrophic factor(BDNF) in injured segments was maintained at a high level after 7–14 days of treatment. In contrast, expression of nerve growth factor(NGF) was down-regulated at 7 days after spinal cord injury. Real-time fluorescence quantitative polymerase chain reaction showed that expression of BDNF and NGF m RNA was induced in injured segments by prednisolone and Jisuikang. At 3–7 days after injury, the effect of prednisolone was greater, while 14 days after injury, the effect of moderate-dose Jisuikang was greater. These results confirm that Jisuikang can upregulate BDNF and NGF expression for a prolonged period after spinal cord injury and promote repair of acute spinal cord injury, with its effect being similar to prednisolone.     

Role of fibronectin in the inhibitory effect of TGF-beta on choline acetyltransferase activity in co-cultures of spinal cord neurons and myotubes.

We have recently shown that the enhanced expression of choline acetyltransferase (ChAT) activity in co-cultures of spinal cord motoneurons and muscle cells was blocked by transforming growth factor-beta (TGF-beta) (Dev. Brain Res., 57, 129-137, 1990). This study was performed to investigate the role of fibronectin in this effect. TGF-beta increased fibronectin level about 2-fold in extracellular matrix of spinal cord cells and skeletal myotubes in culture. Addition of a synthetic polypeptide that competitively inhibits fibronectin binding to its cell surface receptor recovered the TGF-beta-induced suppression of ChAT activity in co-cultures. The polypeptide did not affect ChAT activity in cultures of spinal cord cells alone or in co-cultures without TGF-beta. These results indicate that TGF-beta inhibits the stimulation of ChAT activity in spinal cord neurons in co-culture through a change in the composition and/or amount of fibronectin in the extracellular matrix at neuromuscular contacts.     

Transient decrease of acetylcholinesterase in ventral horn neurons caudal to a low thoracic spinal cord hemisection in the adult rat

Light microscopic enzyme: histochemistry was employed to study the alterations of acetylcholinesterase (AChE) within lumbosacral ventral horn neurons at survival times of 1, 4, 7, 14, 28, 60, and 90 days after low thoracic spinal cord hemisection in adult rats. The intensity of histochemical staining was quantified using densitometric techniques. Virtually all ventral horn neurons of sham-operated and unoperated animals, which served as controls, displayed intense AChE staining. Hemisection of the spinal cord induced a transient, ipsilateral decrease of AChE staining in most neuronal cell bodies and in the neuropil of lamina IX at all segmental levels caudal to the lesion. Quantitative analysis of representative segments revealed a reduction of AChE in the ventral horn during a postoperative (p.o.) period of 1 to 28 days followed by a phase of recovery over the next two months. AChE activity still remained slightly reduced, even at 90 days p.o. The transient decrease in ACNE is a well-known metabolic response of axotomized motoneurons. However, the observed changes of AChE reactivity in intact motoneurons ipsilateral and caudal to the hemisection are presumably induced by the interruption of supraspinal descending pathways. These metabolic changes may functionally affect the whole motor unit and be involved in the disturbances of motor function following spinal cord injury.     

Quantitative analysis of the spinal cord motoneuron under chronic compression: an experimental observation in the mouse

We investigated quantitative changes in spinal cord motoneurons following chronic compression using a mouse model of cervical cord compression. Twenty-five tiptoe-walking Yoshimura (twy) mice with calcified mass lesions compressing the spinal cord posterolaterally at the C1–C2 vertebral levels were compared with five Institute of Cancer Research (ICR) mice that served as controls. Spinal cord motoneurons in the anterior grey horn between the C1 and C3 spinal cord segments were Nissl-stained and counted topographically and then analysed in relation to the extent of spinal cord compression. The number of motoneurons in C1–C3 spinal cord segments decreased significantly with a linear correlation with the transverse area of the spinal cord when the cord was compressed to 50–70% of control values. A significant reduction in the number of motoneurons occurred at the C2–C3 spinal cord segment compressed at the C1–C2 vertebral level. In contrast, at the level rostral to the C1 vertebra, the number of motoneurons increased significantly in proportion to the magnitude of compression. The current study demonstrates that a number of neurons, morphologically consistent with anterior horn cells, were observed at a rostral site absolutely free of external compression where no such cells normally exist.     

Combination of gonadal steroid treatment and peripheral nerve grafting results in a peripheral motoneuron-like pattern of beta II-tubulin mRNA expression in axotomized hamster rubrospinal motoneurons

Rubrospinal motoneurons (RSMN) represent a population of androgen receptor-containing central motoneurons in rodents. In this study, the ability of testosterone propionate (TP), alone or in conjunction with a peripheral nerve graft (PNG), to alter the molecular program of injured RSMN was accomplished using betaII-tubulin cDNA probes and quantitative in situ hybridization (ISH). Initial fluoro-gold labeling experiments following a T1 hemisection established that, as in the rat, the hamster rubrospinal system is essentially crossed and that injured RSMN concentrate in the ventrolateral region of the red nucleus. In the second experimental series, adult gonadectomized male hamsters were subjected to a right T1 hemisection, with half of the operated animals immediately subcutaneously implanted with 1 10 mm TP Silastic capsule and the other half sham implanted. In a third experimental series, animals were subjected to T1 hemisection, followed by transplantation of a predegenerated autologous segment of peripheral nerve. Half of the animals in each group received TP implants at the time of spinal cord injury and PNG. Postoperative times were 2, 7, and 14 days (dpo). Quantitative ISH was performed using a betaII-tubulin-specific (33)P-labeled cDNA probe, emulsion autoradiography, and computerized image analysis for grain counting. Injury alone resulted in a short-lived increase in betaII-tubulin mRNA expression in the RSMN at 2 dpo, with a significant decline to well below control values at 7 and 14 dpo. TP treatment or PNG alone attenuated, but did not prevent, the down-regulation of betaII-tubulin mRNA. In contrast, the combination of TP with a PNG sustained the injury-induced increase in betaII-tubulin mRNA levels throughout the postoperative period of 2, 7, and 14 dpo. The synergistic effects of the two treatment strategies confirm the importance of targeting multiple aspects of the injury response for therapeutic intervention.     

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.     

Phrenic motoneuron expression of serotonergic and glutamatergic receptors following upper cervical spinal cord injury

Following cervical spinal cord injury at C(2) (SH hemisection model) there is progressive recovery of phrenic activity. Neuroplasticity in the postsynaptic expression of neurotransmitter receptors may contribute to functional recovery. Phrenic motoneurons express multiple serotonergic (5-HTR) and glutamatergic (GluR) receptors, but the timing and possible role of these different neurotransmitter receptor subtypes in the neuroplasticity following SH are not clear. The current study was designed to test the hypothesis that there is an increased expression of serotonergic and glutamatergic neurotransmitter receptors within phrenic motoneurons after SH. In adult male rats, phrenic motoneurons were labeled retrogradely by intrapleural injection of Alexa 488-conjugated cholera toxin B. In thin (10μm) frozen sections of the spinal cord, fluorescently-labeled phrenic motoneurons were visualized for laser capture microdissection (LCM). Using quantitative real-time RT-PCR in LCM samples, the time course of changes in 5-HTR and GluR mRNA expression was determined in phrenic motoneurons up to 21 days post-SH. Expression of 5-HTR subtypes 1b, 2a and 2c and GluR subtypes AMPA, NMDA, mGluR1 and mGluR5 was evident in phrenic motoneurons from control and SH rats. Phrenic motoneuron expression of 5-HTR2a increased ~8-fold (relative to control) at 14 days post-SH, whereas NMDA expression increased ~16-fold by 21-days post-SH. There were no other significant changes in receptor expression at any time post-SH. This is the first study to systematically document changes in motoneuron expression of multiple neurotransmitter receptors involved in regulation of motoneuron excitability. By providing information on the neuroplasticity of receptors expressed in a motoneuron pool that is inactivated by a higher-level spinal cord injury, appropriate pharmacological targets can be identified to alter motoneuron excitability.     

Early electrical field stimulation prevents the loss of spinal cord anterior horn motoneurons and muscle atrophy following spinal cord injury

Our previous study revealed that early application of electrical field stimulation(EFS) with the anode at the lesion and the cathode distal to the lesion reduced injury potential, inhibited secondary injury and was neuroprotective in the dorsal corticospinal tract after spinal cord injury(SCI). The objective of this study was to further evaluate the effect of EFS on protection of anterior horn motoneurons and their target musculature after SCI and its mechanism. Rats were randomized into three equal groups. The EFS group received EFS for 30 minutes immediately after injury at T_(10). SCI group rats were only subjected to SCI and sham group rats were only subjected to laminectomy. Luxol fast blue staining demonstrated that spinal cord tissue in the injury center was better protected; cross-sectional area and perimeter of injured tissue were significantly smaller in the EFS group than in the SCI group. Immunofluorescence and transmission electron microscopy showed that the number of spinal cord anterior horn motoneurons was greater and the number of abnormal neurons reduced in the EFS group compared with the SCI group. Wet weight and cross-sectional area of vastus lateralis muscles were smaller in the SCI group to in the sham group. However, EFS improved muscle atrophy and behavioral examination showed that EFS significantly increased the angle in the inclined plane test and Tarlov's motor grading score. The above results confirm that early EFS can effectively impede spinal cord anterior horn motoneuron loss, promote motor function recovery and reduce muscle atrophy in rats after SCI.