Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat

A graded contusion spinal cord injury (SCI) was created in the adult rat spinal cord using the Infinite Horizons (IH) impactor to study the correlation between injury severity and anatomical, behavioral, and electrophysiological outcomes. Adult Fisher rats were equally divided into five groups and received contusion injuries at the ninth thoracic level (T9) with 100, 125, 150, 175, or 200 kdyn impact forces, respectively. Transcranial magnetic motor-evoked potentials (tcMMEPs) and BBB open-field locomotor analyses were performed weekly for 4 weeks postinjury. Our results demonstrated that hindlimb locomotor function decreased in accordance with an increase in injury severity. The locomotor deficits were proportional to the amount of damage to the ventral and lateral white matter (WM). Locomotor function was strongly correlated to the amount of spared WM, which contains the reticulospinal and propriospinal tracts. Normal tcMMEP latencies were recorded in control, all of 100-kdyn-injured and half of 125-kdyn-injured animals. Delayed latency responses were recorded in some of 125-kdyn-injured and all of 150-kdyn-injured animals. No tcMMEP responses were recorded in 175- and 200-kdyn-injured animals. Comparison of tcMMEP responses with areas of WM loss or demyelination identified the medial ventrolateral funiculus (VLF) as the location of the tcMMEP pathway. Immunohistochemical and electromicroscopic (EM) analyses showed the presence of demyelinated axons in WM tracts surrounding the lesion cavities at 28 days postinjury. These data support the notion that widespread WM damage in the ventral and lateral funiculi may be a major cause for locomotor deficits and lack of tcMMEP responses after SCI.     

Hemorrhagic changes in experimental spinal cord injury models

Early hemorrhagic changes in the spinal cord were compared in three experimental spinal cord injury models in the rat in order to determine the nature and consistency of spinal cord hemorrhage following specific and quantitated forces of injury. The spinal cords were injured by weight-dropping, aneurysm clip and extradural balloon compression techniques. Hemorrhagic changes were assessed quantitatively by the image analyser at 1 and 3 hours after injury. Tissue damage was assessed by determining the percentage of total cross sectional area containing hemorrhage. The extent of hemorrhage at site of injury in the clip and balloon preparations was equal, but several times lower in the weight-drop induced injury. Within each experimental group no appreciable differences were observed at the site of injury between the 1 and 3 hours preparations. The variability of damage within experimental groups was most in the weight-dropping and balloon and least in the clip preparations. Differences were also indicated with respect to the distribution of hemorrhage in grey versus white matter. These findings may be of significance when functional recovery is considered in various experimental acute spinal cord injury models.     

Radiation-induced cellular changes in traumatic spinal cord injury

Summary Left dorsal cordotomy at the 11th thoracic vertebra was performed in mature female rats. Local exposures of 1,000 R of 280 kvp x rays were made within 10 min, 12, 24 36 or 48 hrs after injury. Tritiated thymidine (1 Ci/g body wt.) was injected i. v. 1 hr before death and necropsy examination 5, 18 or 30 days after surgery. Hematoxylin-stained sagittal sections (5 ) of the spinal cord were prepared for radioautographic examination. The parameters of magnitude and duration of changes in cell numbers and numbers of cells incorporating tritiated thymidine were determined for scar parenchymal cells (neuroglia and fibroblasts), macrophage, endothelia and mitotic cells.Irradiation modified the cellular composition of the developing scar tissue. These changes were due to a delay of proliferation in scar parenchymal and endothelial cell populations. A concomitant suppression of the number of cells incorporating tritiated thymidine occurred in 5-day old irradiated lesions. The magnitude and duration of these delays varied with the cell type and the time of irradiation after injury.These changes indicate that scar parenchymal and endothelial cells proliferatein situ from progenitor cell populations that were in the lesions at the time of irradiation.Macrophage cell numbers and numbers of these cells incorporating tritiated thymidine were not decreased after irradiation. It is, therefore, probable that the majority of the macrophage cells did not originate from a local progenitor cell population.

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Zusammenfassung Bei erwachsenen weiblichen Ratten wurde eine linksseitige dorsale Chordotomie in Höhe des 11. BWK durchgeführt. Lokale Röntgenbestrahlung mit einer Dosis von 1000 r bei 280 KVP binnen 10 min wurde 12, 24, 36 und 48 Std nach dem Trauma durchgeführt.³H-markiertes Thymidin (1 Ci/kg) wurde 1 Std vor der Tötung i.v. appliziet. Die autoptische Untersuchung erfolgte 5, 18 und 30 Tage nach dem Eingriff. Mit Hämatoxylin gefärbte Sagittalschnitte (5 Dicke) des Rückenmarks wurden autoradiographisch untersucht. Die Parameter der Größe und Dauer der Veränderungen der Zellzahl sowie dez Zahl der³H-Thymidin-markierten Zellen wurden für die Narbenparenchymzellen (Neuroglia und Fibroblasten), Makrophagen, Endothelzellen und Mitosen in der Narbe bestimmt.Die Bestrahlung veränderte die Zellzusammensetzung in dem sich entwickelnden Narbengewebe infolge verzögerter Proliferation der Parenchym- und Endothelzellen. In 5 Tage alten bestrahlten Läsionen erfolgte eine gleichzeitige Verminderung der³H-Thymidin inkorporierenden Zellen. Die Stärke und Dauer dieser Verzögerung schwankte je nach Zelltyp und Bestrahlungszeit nach dem Trauma.Die Befunde sprechen dafür, daß Narbenparenchyn- und Endothelzellen bei der Narbenbildung in situ aus ortsständigen Zellpopulationen gebildet werden, die bereits zum Zeitpunkt der Bestrahlung in der Läsion vorliegen.Die Zahl der Makrophagen sowie der³H-Thymidin-inkorporierenden Zellen war nach der Bestrahlung nicht vermindert. Es ist daher wahrscheinlich, daß die Mehrzahl der Makrophagen nicht aus ortsständigen Zellvorläufern entsteht.

     

Hip-phase-dependent flexion reflex modulation and expression of spasms in patients with spinal cord injury

The flexion reflex in human spinal cord injury (SCI) is believed to incorporate interneuronal circuits that consist elements of the stepping generator while ample evidence suggest that hip proprioceptive input is a controlling signal of locomotor output. In this study, we examined the expression of the non-nociceptive flexion reflex in response to imposed sinusoidal passive movements of the ipsilateral hip in human SCI. The flexion reflex was elicited by low-intensity stimulation (300 Hz, 30 ms pulse train) of the right sural nerve at the lateral malleolus, and recorded from the tibialis anterior (TA) muscle. Sinusoidal hip movements were imposed to the right hip joint at 0.2 Hz by a Biodex system while subjects were supine. The effects of leg movement on five leg muscles along with hip, knee, and ankle joint torques were established simultaneously with the modulation pattern of the flexion reflex during hip oscillations. Phase-dependent modulation of the flexion reflex was present during hip movement, with the reflex to be significantly facilitated during hip extension and suppressed during hip flexion. The phase-dependent flexion reflex modulation coincided with no changes in TA pre- and post-stimulus background ongoing activity during hip extension and flexion. Reflexive muscle and joint torque responses, induced by the hip movement and substantiated by excitation of flexion reflex afferents, were entrained to specific phases of hip movement. Joint torque responses were consistent with multi-joint spasmodic muscle activity, which was present mostly during the transition phase of the hip from flexion to extension and from mid- to peak extension. Our findings provide further evidence on the interaction of hip proprioceptors with spinal interneuronal circuits engaged in locomotor pathways, and such interaction should be considered in rehabilitation protocols employed to restore sensorimotor function in people with SCI.     

Photochemically induced spinal cord injury in the rat

We have developed in the rat a minimally invasive model of reproducible spinal cord injury initiated photochemically. With the exposed spinal column intact, 560 nm irradiation of the translucent dorsal surface induces excitation of the systemically injected dye, rose Bengal, in the spinal cord microvasculature. The resultant photochemical reaction leads to vascular stasis. Histopathological changes at 7 days include hemorrhagic necrosis of the central gray matter, edematous pale-staining white matter tracts and vascular congestion. At the level of cord irradiation (T8) the entire cord thickness is necrosed except for the periphery of the anterior funiculus. Voluntary motor function is consistently lost in the subacute phase of injury.     

A nonrandom interneuronal pattern in the developing frog spinal cord

In the developing spinal cord of the frog, Xenopus laevis, a population of interneurons assumes a pattern that represents a previously undescribed level of organization. Glyoxylic acid treatment and immunocytochemistry show that the neurons contain catecholamines and their synthetic enzyme, tyrosine hydroxylase. Cells are located within the ependymal layer of the floor plate region of the larval spinal cord. The cells have several processes including a long one that projects toward the brain without fasciculating with other labeled processes. In addition, the cytoplasm of the catecholaminergic cells extends into the central canal, showing that they are a population of cerebrospinal fluid-contacting neurons. The spatial domain of catecholaminergic neurons starts abruptly at the boundary between the hindbrain and spinal cord and continues to the tip of the tail. The neurons occupy two longitudinal columns within the sheet of floor plate cells, which includes cells that do not exhibit the catecholaminergic phenotype. Unlabeled cells are intercalated between catecholaminergic cells in each column, giving the labeled cells the appearance of being spaced along the length of the spinal cord. This general arrangement is evident at the time of hatching. Spatial analysis showed that the position of cells along a column is not random. The nonrandom behavior is due to cells being excluded from the area immediately surrounding other catecholaminergic cells. Further analysis showed that the cellular pattern lacks segmental or other periodic repeats. Ultimately, the location of a cell within a column depends upon the position of its closest catecholaminergic neighbor. © 1993 Wiley-Liss, Inc.     

Motor cortex changes in spinal cord injury: a TMS study

Using paired pulse transcranial magnetic stimulation (TMS) paradigms, we studied cortical excitability in a patient with spinal cord lesion. During posterior tibial nerve stimulation, the contextual flexion of hand fingers contralateral to the stimulated lower limb had suggested a change in motor cortex excitability. Results showed a decrease in the activity of motor cortex inhibitory circuits. This could suggest that in spinal cord injury, just as in stroke and peripheral deafferentation, a disinhibition of latent synapses within the motor cortex and the rewriting of a new motor map can occur.     

Upper gastrointestinal motility changes following spinal cord injury

Abstract  Spinal cord injury (SCI) is associated with severe autonomic dysfunction in both the acute and chronic phases. Upper gastrointestinal (GI) motor dysfunction has been previously reported in humans and rats. Gastric emptying (GE) of a solid meal – as measured by the [¹³C]-octanoic acid breath test – is delayed in the first 3 weeks after either spinal cord transection (SCT) or contusion (SCC) in rats. This is one of the main findings of a new paper by Qualls-Creekmore et al. in the current issue of this journal. Previous studies in rats only reported impairment of GE, intestinal and GI transit of liquid after SCI, but the authors observed that the delay of the GE of solid was more prominent after SCT than SCC. Recovery of the delay of GE of solid occurred at 6 weeks after SCC, but not after SCT. However, gastric motility changes persisted despite the functional normalization of the GE in rats with SCC. Bowel dysfunction is a major physical and psychological burden for SCI patients. Collaborative efforts, like the development of international standards to evaluate autonomic function after SCI will likely clarify the mechanisms of dysfunction and lead to the development of new therapeutic strategies.     

组织工程脊髓移植治疗大鼠脊髓半切块状损伤

目的 研究组织工程脊髓移植治疗大鼠脊髓半切块状损伤的疗效.方法 以聚乳酸-羟基乙酸(PLGA)为细胞支架,多聚赖氨酸为细胞外基质,神经十细胞(NSCs)为种子细胞,体外构建组织工程脊髓.制作大鼠T10脊髓右半切块状损伤模型,随机分成3组:实验组在损伤区移植组织工程脊髓,对照组A移植NSCs,对照组B移植PLGA.移植治疗12周,每周均行BBB评分定量评价肢体运动功能.伤后第12周辣根过氧化物酶(HRP)神经逆行示踪评价脊髓传导束的恢复程度,并取损伤处脊髓组织行免疫组织化学染色,观察移植区的形态结构修复.结果 伤后12周实验组的BBB运动功能评分较对照组明显提高,差异有统计学意义(P＜0.05).HRP神经逆行示踪显示:实验组鼠右侧大脑组织中可见大量的HRP标记阳性神经元,而两对照组仅见有少量HRP阳性神经元;免疫组织化学染色显示:实验组移植区NF阳性神经元和GAP-43阳性神经轴索数量较多,修复了缺损,而对照组极少,仍留下不同程度的缺损.结论 组织工程脊髓移植治疗促进了半切块状损伤脊髓的形态结构修复和功能恢复,疗效明显优于单纯的NSCs移植和PLGA移植.     

缺氧诱导因子-1a在大鼠脊髓缺血再灌注损伤中的表达

目的观察缺氧诱导因子-1α（HIF-1α）在大鼠脊髓缺血再灌注损伤（SCII）中的表达变化及其意义。方法制备大鼠脊髓缺血再灌注损伤模型,分别于再灌注后8h、12h、24h,3d和5d取腰骶段的脊髓,以假手术组大鼠相同阶段的脊髓为对照,采用Westernblot法和免疫组织化学检测伤后脊髓组织中HIF-1α的表达变化。结果再灌注8h左右HIF-1α在整个脊髓灰质开始表达上调,在24h达峰值,在伤后3d表达回落,5d显著减少,灰度值在8h、12h、24h,3d和5d不同时相,分别为（211．39±5．58）μm2,（184．53±6．56）μm2,（167．39±5．76）μm2,（198．44±3．98）μm2和（228．39±2．87）μm2,分别与假手术组比较差异有显著性意义（P〈0．05）。HIF-1a在灰质中的表达以中央管周围和前角、后角最为显著。再灌注24h和3dHIF-1a在脊髓白质出现弱的表达,灰度值分别为（238．154-6．87）μm2和（236．87±7．41）μm2,分别与假手术组比较差异有显著性意义（P〈0．05）。但在白质后索,HIF-1a的表达相对较强。HIF-1α在灰质中主要定位于神经元和星形胶质细胞,在白质中主要定位于神经胶质细胞。结论脊髓缺血再灌注损伤后,HIF-1α呈现时序性的表达变化,这可能是脊髓缺血再灌注损伤的重要适应性调节机制之一。     

Immunocomplexes in rat and rabbit spinal cord after injury

The possibility that, following a major lesion of the central nervous system, a humoral immune response could be evoked with formation of immune complexes "in situ" was investigated. For this purpose, an immunohistochemical study on rabbit and rat spinal cord at different times after surgical transection was carried out. The peroxidase-antiperoxidase method showed IgG decoration of the myelin sheaths starting a short time after surgery. The sera of intact and injured animals were then tested both by immunohistochemical methods on intact spinal cord sections and by immunoelectrophoresis on a protein extract of homologous spinal cord. The results showed in the rabbit the absence of antibodies to neural antigens before surgical injury and its appearance within a few days after surgery. On the other hand, in the rat, even before the injury, we found antibodies to neural tissue which decreased in the first few hours after injury, and returned to control values during successive days. The same experiments were conducted after a peripheral nerve lesion (sciatic nerve crush), but no immune response could be detected. The possible role of this immune response in the failure of axonal regeneration in mammalian spinal cord is briefly discussed.     

Age related changes of enkephalin in rat spinal cord

Met-enkephalin immunoreactive material content was found to be decreased in the cervical and thoracic segments of the spinal cord from rats aged 25 months as compared to young, 3-month-old, rats. No age-related variations were detectable at the lumbar level. Bio-Gel P 30 column chromatography of thoracic segment extracts indicates that the composition of the immunoreactive material is similar in the two age-groups investigated. At the thoracic level opiate receptor binding was also measured. Opiate receptor number is increased in the thoracic segments of the spinal cord from older rats. These age-related changes in immunoreactive Met-enkephalin content and opiate receptor number at spinal levels may contribute to determine an altered pain sensitivity during aging.     

Local spinal cord glucose utilization and extracellular potassium activity changes after spinal cord injury in rats

Spinal microenvironment and metabolic alterations after experimental contusional injury of the spinal cord were evaluated in the same Wistar rats. Severe spinal cord injury was made under light GOF anesthesia with a 10 g weight drop onto the exposed Th-8 spinal cord from a 10 cm height and then halothane was ceased. The author studied extracellular potassium activity ([K+]e) and DC potential for 2 hours after paraplegic spinal cord injury in conscious rats. Furthermore, at 2 hours after cord injury, local spinal cord glucose utilization (1-SCGU) was measured with quantitative autoradiographic 2-[14C] deoxy-glucose method (Sokoloff et al.). [K+]e in injured spinal cords was 59 +/- 5 (mean +/- S.E.M.) mEq at 10 min after injury and was cleared with an exponential half-life of 1 hour. At 2 hours after injury [K+]e was still high with a value of 16 +/- 1 mEq compared with 4 mEq of control animals. DC potential changes was a mirror image of that of [K+]e. DC potential changed by a mean of 10.7 mV positively from 10 min. to 2 hours after injury. 1-SCGU at the impact site was extremely low in both white and gray matters. At 6mm rostral from the impact center 1-SCGU was remarkably reduced in the gray matter, and in the lateral white matter. But at 3 mm rostral 1-SCGU was well preserved. And at 20 mm rostral there was no difference in 1-SCGU with control animals. Massive potassium efflux from the injured spinal cord to the adjacent spinal segment was clarified at this experiment.(ABSTRACT TRUNCATED AT 250 WORDS)     

1H-MRS in spinal cord injury: acute and chronic metabolite alterations in rat brain and lumbar spinal cord

A variety of tests of sensorimotor function are used to characterize outcome after experimental spinal cord injury (SCI). These tests typically do not provide information about chemical and metabolic processes in the injured CNS. Here, we used (1) H-magnetic resonance spectroscopy (MRS) to monitor long-term and short-term chemical changes in the CNS in vivo following SCI. The investigated areas were cortex, thalamus/striatum and the spinal cord distal to injury. In cortex, glutamate (Glu) decreased 1 day after SCI and slowly returned towards normal levels. The combined glutamine (Gln) and Glu signal was similarly decreased in cortex, but increased in the distal spinal cord, suggesting opposite changes of the Glu/Gln metabolites in cortex and distal spinal cord. In lumbar spinal cord, a marked increase of myo-inositol was found 3 days, 14 days and 4 months after SCI. Changes in metabolite concentrations in the spinal cord were also found for choline and N-acetylaspartate. No significant changes in metabolite concentrations were found in thalamus/striatum. Multivariate data analysis allowed separation between rats with SCI and controls for spectra acquired in cortex and spinal cord, but not in thalamus/striatum. Our findings suggest MRS could become a helpful tool to monitor spatial and temporal alterations of metabolic conditions in vivo in the brain and spinal cord after SCI. We provide evidence for dynamic temporal changes at both ends of the neuraxis, cortex cerebri and distal spinal cord, while deep brain areas appear less affected.     

Cellular changes during repair of a cryogenic spinal cord injury in the rat: an electron microscopic study

Cryogenic injury of adult, rat spinal cord was produced under controlled non-invasive conditions to study repair and regeneration in adult, mammalian central nervous tissue in which tissue continuity and integrity are relatively preserved. Under these experimental conditions axons and myelin are destroyed, a matrix of glial cells is preserved, and regrowth of axons is apparent. Electron microscopic studies at 7, 15, 30 and 60 days post-injury demonstrate axonal structures indicative of regrowth, astrocytic structures which appear to provide support to both matrix and axons and myelination of axons by both oligodendrocytes and Schwann cells. These cellular events restore much of the normal structure within the injured area up to its junction with the Wallerian zone. In this junctional zone morphologic evidence may indicate continuing cellular activity, even at 60 days, in axons, astrocytes and myelinating cells. These studies suggest that under ideal conditions damaged axons may be capable of regeneration within the adult mammalian central nervous system and that this model provides an opportunity to define some of the mechanisms.     

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.     

Neuronal and glial changes in the rat phrenic nucleus occurring within hours after spinal cord injury

The present study describes specific morphological changes in the normal ultrastructure of the rat phrenic nucleus which occur within 4 hours after an ipsilateral spinal cord hemisection rostral to the nucleus. Phrenic neurons were identified at EM levels by retrograde HRP labeling. Ultrastructural features of the phrenic nucleus in uninjured animals and at 4 hours and 1, 2, and 4 days after injury were qualitatively analyzed and then quantitated with a computerized morphometric system. Our results indicated that by 4 hours posthemisection, there was a significant increase in the number of double synapses. Furthermore, the number of double synapses remained significantly higher than normal at all the other posthemisection periods. A significant increase in the length of dendrodendritic membrane appositions was also noted as early as 4 hours posthemisection. The mean normal appositional length of 1.42 +/- 0.09 microns increased to 1.89 +/- 0.12 microns at 4 hours and further increased to 2.20 +/- 0.20 microns by 1 day posthemisection. The increase in the length of membrane appositions was most likely due to an active retraction of astroglial processes from their normal position in between the dendrites. Although there was an increase in the mean length of the dendrodendritic appositions, the mean percentage of the appositions (expressed as the total number of appositions divided by the total number of dendrites in each sample) was not increased significantly over normal values during the early posthemisection periods. By 2 and 4 days posthemisection, however, the percentage of dendrodendritic appositions increased to significantly higher values than normal. Normally, 4.68 +/- 0.69% of the dendrites in the phrenic nucleus were found to be in apposition, and this number increased significantly to 7.27 +/- 1.06% by 2 days and 7.46 +/- 0.79% by 4 days posthemisection. At these later posthemisection periods, the mean length of the appositions decreased to levels which were no longer significantly higher than normal. A distribution analysis of the length of each dendrodendritic apposition in both the normal and spinal hemisected rats showed that there were more dendrodendritic appositions in the phrenic nucleus at the later posthemisection periods. It also showed that their mean length was decreased because many of the new appositions were relatively short. The above neuronal and glial alterations of the phrenic nucleus have never before been described as a response to injury of the mammalian spinal cord. Furthermore, the possibility that the above changes could represent the morphological substrate for the unmasking of functionally ineffective synapses in ou     

Extracellular space volume changes in the rat spinal cord produced by nerve stimulation and peripheral injury

Double-barrelled potassium and tetramethylammonium-sensitive microelectrodes were used in diffusion studies with tetramethylammonium ions, which remain essentially extracellular during the measurements. Activity-related changes in the extracellular space (ECS) volume fraction (), ECS tortuosity (γ) and the dynamics of the ECS volume changes were examined in the spinal dorsal horns of rats. The and γ in L₄ and L₅ segments of unstimulated rats werea = 0.24 ± 0.01 (i.e. ECS occupied24 ± 1% of the total spinal cord volume) andγ = 1.54 ± 0.04 (mean ± S.D. of mean, n = 21). The values were not significantly different throughout the dorsal horn. Repetitive electrical stimulation of peripheral nerves at 3-100 Hz increased extracellular potassium concentration ([K⁺]_e) and ECS volume in Rexed laminae III-V by15.8 ± 2.7% (n = 5). After the end of stimulation, when the [K⁺]_e decreased below the original baseline (K⁺ undershoot), the ECS volume decreased by 20–45%. The magnitude and duration of ECS volume decrease were positively related to the stimulation frequency and duration. The ECS volume decrease was maximal at 2–10 min after the stimulation had been discontinued, and it returned to the prestimulation values in 15–40 min. The ECS volume decreased by 20–50% after injury of the ipsilateral hind paw evoked either by subcutaneous injection of turpentine (n = 5), or by thermal injury (n = 6). The maximal changes were found in Rexed laminae III–V, 5–10 min after injection of turpentine and 10–25 min after thermal injury, and persisted for more than 120 min and 30 min, respectively. The tortuosity of the ECS was not significantly altered by stimulation or injury. Our measurements indicate that the dynamic changes in the spinal cord ECS volume accompany transmembrane ionic shifts during and long after neural activity which had been evoked by peripheral stimulation or injury.