Changes in physical strain and physical capacity in men with spinal cord injuries

To determine longitudinal changes in physical capacity and physical strain during activities of daily living (ADL), 37 men with spinal cord injuries (C4/5-L5) performed an exercise test and various ADL on two occasions (T1 and T2; interval 34.5 +/- 1.5 months). Parameters of physical capacity were aerobic power (VO(2peak)) and maximal power output (PO(max)). Physical strain was estimated by the heart rate response relative to the heart rate reserve. VO(2peak) at T2 (1.75 +/- 0.55 1*min(1)) did not significantly differ from that at T1 (1.67 + 0.47 1*min(-1)). Absolute PO max improved (P < 0.05) from 64.9 +/- 25.9 (T1) to 71.7 +/- 27.2 W (T2), whereas relative PO(max) did not change. Activity level, time since injury, change in body mass, and occurrence of rehospitalization were the most important predictors of changes in physical capacity. Changes in relative VO(2peak) were related (P < 0.05) to changes in strain during transfers to the shower wheelchair (r = -0.39) and shower seat (r = -0.46), and during the curb ascent (r = -0.47). In conclusion, the hypothesized decline in physical capacity did not occur over the 3-yr period. Maintenance of physical capacity, which may in part be achieved through sport participation and improved medical care, together with avoidance of excessive body mass, may be useful to prevent high levels of strain during ADL.     

CDR3 size spectratyping and sequencing of spectratype-derived TCR of spinal cord T cells in autoimmune encephalomyelitis

To characterize the nature of autoimmune disease-inducing T cells in the target organ, oligoclonal expansion of spinal cord T cells of Lewis rats with experimental autoimmune encephalomyelitis (EAE) was examined by complementarity-determining region 3 (CDR3) size spectratyping. It is known that TCR of in vitro-established myelin basic protein-specific T cell clones and lines have a short CDR3 and that the amino acid sequence in this region is highly preserved. On the basis of these findings, we analyzed 22 spectratypes of the TCR beta-chain (Vbeta1-20). Among them, only Vbeta8.2 and Vbeta17 showed oligoclonal expansion of TCR with a short CDR3 at the early stage of EAE. More interestingly, the spectratype profile of Vbeta8.2 seen at the early stage was preserved throughout the course of EAE, whereas that of Vbeta17 became more diverse at the peak stage of the disease. Analysis of nucleotide and predicted amino acid sequences of Vbeta8.2 CDR3 derived from the spectratypes revealed that the clones with CASSDSSYEQYFGPG, which is one of the representative sequences of encephalitogenic T cell clones, constituted the predominant population not only at the early stage but also at the peak and recovery stages (71, 71, and 60%, respectively). These findings imply that although the phenotype of T cells in the target organ diversifies as the autoimmune disease progresses, disease-associated TCR spectratype(s) are preserved throughout the course of the disease. Thus, CDR3 size spectratyping is a powerful tool for the screening of disease-inducing T cells in an autoimmune disease of unknown pathomechanism.     

Nitric oxide and the immunomodulation of experimental allergic encephalomyelitis

Previous studies examining the effect of nitric oxide synthase (NOS) inhibition on the course of experimental allergic encephalomyelitis (EAE) have yielded conflicting results. This may relate to the use of nonspecific inhibitors and to differences between active and adoptive EAE. We examined the effect of treatment with L-N-(1-iminoethyl)lysine (L-NIL), a selective inhibitor of the cytokine-inducible isoform of NOS, on the clinical course of active and adoptive EAE in Lewis rats. We find that while L-NIL treatment of recipients is protective in adoptive EAE, treatment of active EAE with L-NIL leads to a marked accentuation of disease expression. In L-NIL-treated animals treated with myelin basic protein/complete Freund's adjuvant (MBP/CFA), disease onset is accelerated and clinical symptoms are more severe. Accentuation of integrated disease scores is seen even if L-NIL treatment is started 5 days following immunization. The histological findings in involved spinal cords from L-NIL-treated animals with active EAE are similar to those from untreated animals with similar clinical scores. L-NIL treatment of MBP/CFA-immunized animals does not prevent recovery from clinical symptoms, nor does it allow for reinduction of disease in animals previously immunized with MBP/CFA. Treatment of F344 rats, a strain which is relatively nonsusceptible for EAE, with L-NIL results in consistent evidence of EAE following immunization with MBP/CFA. These findings, together with our previous work on interstitial nephritis, support a role for endogenously generated NO in immunoregulation of T cell responses following immunization with antigen in CFA, and suggest that inducibility of NOS expression may be an important susceptibility factor for autoimmunity.     

Changes in brain and spinal cord water content during recurrent experimental autoimmune encephalomyelitis in female Lewis rats

Regional changes in percent water content, a measure of regional levels of edema, were determined in female Lewis rats during key stages of recurrent experimental autoimmune encephalomyelitis (rEAE). The changes in percent water content of the spinal cord and brainstem closely paralleled the clinical and, to a lesser extent, histological course of rEAE (increasing during exacerbations and decreasing during remissions), whereas the percent water content of the forebrain, thalamus/midbrain, hypothalamus, and cerebellum remained constant and equal to control levels at all stages of the disease process. These results suggest that edema formation and resolution in the brainstem and spinal cord may be significant determinants of the transient and recurrent course of neurological dysfunction exhibited by rats with rEAE.     

Effects of caudal traction of the spinal cord on evoked spinal cord potentials in the cat

This study attempts clarify the mechanism of neurological deficits in tethered cord syndrome using evoked spinal cord potentials (ESCPs). ESCPs in response to both sciatic nerve (SN-ESCP) and spinal cord stimulation (SC-DESCP) were recorded from the dorsal epidural space. With a fixed degree of caudal traction on the spinal cord in ten cats for 2-4 hours, ESCPs were increased in amplitude in the N1 and N2 deflections of the SC-DESCPs to 158% and 154% at L5 and decreased to 91% and 76% after transient augmentation at L3. On the other hand, the amplitude in the N1 deflection of the SN-ESCPs at L3 and L5 was decreased to 40% and 68%. These findings suggest that not only the force but also the duration of traction influence the degree of the spinal cord dysfunction. When the spinal cords of 17 cats received compression with traction and without traction, the SN-ESCPs of the former became positive earlier than that of the latter. The extent of the recovery in amplitude of both SC-DESCPs and SN-ESCPs propagated over compression site was far limited in the former than in the latter. These results would indicate that the spinal cord subjected to traction is vulnerable to compression.     

Nitric oxide localized to spinal cords of mice with experimental allergic encephalomyelitis: an electron paramagnetic resonance study

Experimental allergic encephalomyelitis (EAE) is a demyelinating autoimmune disorder that can be induced in susceptible mice by T lymphocytes sensitized to central nervous system (CNS) myelin components and is a prime animal model for the human CNS demyelinating disorder, multiple sclerosis (MS). Although CNS inflammation in which T lymphocytes and activated macrophages are the predominant cell types is observed in mice with EAE and in humans with MS, the exact mechanisms underlying the CNS damage and demyelination are not understood. Nitric oxide (NO), a gaseous free radical, has recently been shown to be a cytolytic product of activated macrophages. Using electron paramagnetic resonance spectroscopy, the nitric oxide free radical complexed with iron-sulfur proteins has been identified in affected spinal cords of mice with EAE, concurrent with the diminution of iron-sulfur proteins. These results indicate NO may play a role in the disease process of EAE, and perhaps MS.     

Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat

Acute, monophasic experimental allergic encephalomyelitis (EAE) in the Lewis rat shows pathological similarities to the human disease multiple sclerosis (MS). Rats that recover from EAE are essentially resistant to disease reinduction, unlike MS in which relapses are frequently associated with common bacterial and viral infections. As macrophage-derived interleukin (IL)-12 is a critical component of innate resistance to bacterial infection and appears to directly activate encephalitogenic T cells in vivo, the ability of this cytokine to reinduce paralysis in EAE was examined. Paralytic disease was exacerbated by intraperitoneal IL-12 administration and could be reinduced up to 1 week after recovery from the primary clinical episode. Concomitant with worsening of initial clinical signs and relapse was an increase in the ratio of macrophages to T cells in brain stem perivascular cuffs and the expression of inducible nitric oxide synthase in cells with both macrophage and microglial morphology. These findings suggest that IL-12 may contribute to macrophage-mediated disease exacerbation and relapse in patients with MS.     

Effect of spinal cord transection on N-methyl-D-aspartate receptors in the cord

Spinal cord injury can lead to an exaggeration of transmission through spinal pathways, resulting in muscle spasticity, chronic pain, and abnormal control of blood pressure and bladder function. These conditions are mediated, in part, by N-methyl-D-aspartate (NMDA) receptors on spinal neurons, but the effects of cord injury on the expression or function of these receptors is unknown. Therefore, antibodies to the NMDA-R1 receptor subunit and binding of [3H]MK-801 were used to assess NMDA receptors in the spinal cord. Receptor density in rats with intact spinal cords was compared to that in rats 1 and 2 weeks after spinal cord transection (SCT) at the mid-thoracic level. At 1 and 2 weeks after SCT, [3H]MK-801 binding was reduced in most laminae in cord segments caudal to the injury, whereas no decrease in amount of R1 subunit immunoreactivity was observed. No significant changes in [3H]MK-801 binding and NMDA-R1 immunoreactivity could be seen rostral to the transection. Since [3H]MK-801 binding requires an open ion channel, the discrepancy between [3H]MK-801 binding and immunocytochemistry may indicate a loss of functional receptors without a consistent change in their total number. Therefore, the exaggerated reflexes that are well established in rats 2 weeks after cord injury must be mediated by a mechanism that withstands attenuation of NMDA receptor function.     

Epidural spinal cord stimulation in the management of spasms in spinal cord injury: a prospective study

Forty-eight spinal cord injury victims were implanted with an epidural spinal cord stimulation system to treat spasms that had not satisfactorily responded to medical therapy. All the patients were at least 6 months after the injury. The protocol included assessment by independent examiners preoperatively and at 3, 6, 12 and 24 months after the implant. Pre- and postoperative data collection included the frequency and severity of the spasms. Combining the frequency and intensity scores into a 'severity' score provided a more accurate clinical picture. No patient observed neurological deterioration following the surgical procedure or the neurostimulation treatment. A statistically significant reduction in the severity of the spasms was observed in the follow-up evaluations, with results that progressively increased in time. It is appears that spinal cord stimulation is an effective and safe alternative in the management of spasms in spinal cord injury victims. Its exact role in relation to intrathecal baclofen infusion and ablative procedures remains to be defined.     

Magnetic resonance imaging of PLP-induced experimental allergic encephalomyelitis in Lewis rats

Despite epidemiological studies indicating a positive relationship between alcohol and stroke, little is known with regard to effect of chronic alcohol on neuronal injury after stroke. In this study, we examined the effect of chronic ethanol on mRNA levels of sarcoplasmic or endoplasmic Ca2+-ATPase (SERCA2b) and inositol 1,4, 5-triphosphate receptor (IP3R1) in gerbils subjected to global cerebral ischemia induced by ligation of both common carotid arteries. Gerbils were given daily by intragastric intubation either a liquid diet containing ethanol (4 g/kg) or the same diet with an isocaloric amount of sucrose for 35 days. They were subsequently subjected to a 5 min ischemic insult followed by reperfusion for 48 h. In agreement with other studies, ischemic insult caused significant decreases (P<0.05) in mRNA levels of both IP3R1 and SERCA2b in the hippocampal CA1 region but not in the dentate gyrus. Nevertheless, despite a significant (P<0.05) decrease in SERCA2b mRNA in the Purkinje neurons, chronic ethanol did not alter the expression of this mRNA species in the hippocampal CA1 neurons nor did it alter the decrease in SERCA2b mRNA due to cerebral ischemic insult. Since IP3R1 and SERCA2b are key mediators for regulation of intracellular Ca2+ stores, the decrease in SERCA2b mRNA but not IP3R1 mRNA in cerebellar neurons may be an important mechanism underlying alteration of calcium homeostasis and cerebellar degeneration upon chronic ethanol consumption.     

Electrophysiology of barbiturate withdrawal in the spinal cord

Cats were made physically dependent on sodium pentobarbital using the "maximally tolerable" dosing technique. All animals treated this way receive equieffective doses chronically and all become severly dependent. After 5 weeks of treatment each cat displayed withdrawal signs indicative of severe physical dependence. At specific times after the last dose, electrophysiological measurements of spinal cord segmental reflex function were made. Under brief volatile anesthesia, a C1 spinal section was performed. The lumbar spinal cord was exposed by laminectomy and a hindleg was dissected to provide peripheral nerves for stimulation. Recordings were taken from ventral roots L7 and S1 that had been cut near their exits through the dura. Following single, supramaximal sciatic nerve shocks, monosynaptic (2N) responses were not altered during withdrawal, but both the amplitude and duration of polysynaptic response and of afterdischarge were increased withdrawing cats. The rate of 2N synaptic recovery, measured by a paired stimuli technique, was found to be increased during withdrawal. The 2N pathway was able to transmit more effectively during repetitive stimulation since there was less decrement in response during transmission. The relationship between post-tetanic potentiation and tetanic frequency was shifted toward lower frequencies. The size of the motor neuron pool, estimated by maximum post-tetanic potentiation, and the 2N discharge zone were not altered. Background discharge ("noise") was increased during withdrawal.     

Iron deposits in the central nervous system of SJL mice with experimental allergic encephalomyelitis

Iron has been proposed to promote oxidative tissue damage in multiple sclerosis (MS). In order to gain insights about how iron gets processed during MS, the deposition of iron was investigated in the CNS of mice with experimental allergic encephalomyelitis (EAE), which is a commonly used animal model of MS. Control mice (adjuvant only) and EAE mice (myelin basic protein plus adjuvant), were sacrificed at 4-8 days (preclinical phase), 10-13 days (clinical phase), or 18 days (recovery phase) post injection. Sections from the cerebrum, hindbrain, and cervical, thoracic and lumbar spinal cord were stained as previously described (J. Neurosci. Res. 29:413, 1991), and scored blindly for histopathological staining. There was minimal histopathological staining at any age in control animals or during the preclinical stage in EAE animals. At the clinical stage of EAE, stained pathological features (macrophages, extravasated RBC and granular staining) were significantly increased compared to the preclinical stage. In the recovery phase, macrophage and granular staining persisted but there was loss of extravasated RBC. Dual labeling studies revealed that granular deposits were present in astrocytes and in locations that appeared to be extracellular. In order to gain insights about the origin of iron deposits in EAE mice, additional studies were performed on brains of mice with extravasated blood lesions. These brains had granular, macrophage and RBC staining. Thus, each of the stained features in EAE animals could be due to the extravasation of blood which occurs in the SJL model of EAE, although some of the iron could have originated from myelin and oligodendrocytes damaged during EAE.     

Intramedullary cavernous malformations of the spinal cord

Cavernous malformations of the spinal cord are extremely rare lesions. The 58 reported cases in the English literature and 9 of the authors' own cases are reviewed. The clinical presentation, patient characteristics, radiographic appearance, and histopathologic features are reviewed. The optimal surgical management and outcomes of treatment for intramedullary spinal cord cavernous malformations are discussed in detail.     

The effect of prolonged spinal cord compression on the extent of morphological changes in experimental spinal cord injury in rabbits

The analysis of early spinal cord decompression influence on the extent of morphological and microvascular changes after traumatic cord injury was the subject of this study, carried out on Polish-breed rabbits divided into two groups. Microvascular changes were evaluated in the first group of 20 animals and morphological changes in the second group of 36 rabbits. The injury causing paraplegia was performed at D9-D10 level by Allen method modified. Every group was subdivided into 4 subgroups depending on the duration of cord compression 2, 4, 6 and 12 hours. Fragments of cord were taken for examination 12 hours after decompression, from sites 0.5, 1.0 and 1.5 cm distant from the injury level. Histopathological analysis was performed by light and electron microscopy and for the analysis of microcirculation with microangiography the Górkiewicz method was used. Great changes were found in nerve fibres, vascular endothelium and microcirculation. The most pronounced lesions were found in the subgroup with 6-hour compression, in the form of haemorrhage, central necrosis and oedema within and around axona as well as destruction of myelin sheaths. Early decompression (within 6 hours) can reduce the extent of morphological and vascular changes.