Effect of hypertonic saline on leukocyte activity after spinal cord injury

STUDY DESIGN: The effect of intravenous administration of hypertonic saline on leukocyte adhesion after compression injury of the spinal cord was evaluated. OBJECTIVES: To investigate changes in leukocyte adhesion after spinal cord injury and to evaluate the effect of hypertonic saline on this process. SUMMARY OF BACKGROUND DATA: Leukocytes have been thought to exacerbate tissue injury after ischemia-reperfusion. Downregulating and reducing the number of circulating leukocytes has attenuated tissue damage in various models of cerebral ischemia. Recently, investigators have reported that leukocytes exacerbate injury in the spinal cord after trauma. Other recent findings have indicated that hypertonic saline may play a role in decreasing leukocyte adhesion and activation. METHODS: Sprague-Dawley rats were anesthetized, and a C3-C5 laminectomy was performed. Injury was caused by 35 g of compression applied to the cord for 10 minutes. Animals were divided into three groups: sham treated, untreated, and treated. The treated animals received 7.5% hypertonic saline (5 mL/kg, intravenously) 5 minutes after the injury. Sticking leukocytes and shear rate were measured using fluorescence microscopy. RESULTS: Administration of 7.5% hypertonic saline after injury significantly decreased the number of sticking leukocytes in the venules and arterioles. Shear rate was unchanged between the groups. CONCLUSIONS: The results show that an increase in leukocyte adhesion after a compressive injury is attenuated by the administration of 7.5% hypertonic saline. The decrease in adhesion cannot be attributed to changes in the shearing forces, because no significant change was observed in the shear rate. Hypertonic saline may interfere with leukocytes directly by interfering with their ability to swell and thus may prevent activation.     

Effect of spinal cord injury on the permeability of the blood-brain and blood-spinal cord barriers to the neurotropin PACAP

BACKGROUND & AIMS: The association of prazosin to propranolol enhances the decrease in portal pressure but may cause hypotension and sodium retention. The aim of this study was to compare the portal pressure reduction and safety of the combination of propranolol plus prazosin with that of propranolol plus isosorbide-5-mononitrate (ISMN). METHODS: Fifty-six portal-hypertensive cirrhotics received randomly propranolol plus prazosin (n = 28) or propranolol plus ISMN (n = 28) orally for 3 months. Hemodynamics and liver and renal function were assessed at baseline and after 3 months. RESULTS: Propranolol plus prazosin caused a greater reduction in hepatic venous pressure gradient (HVPG) than propranolol plus ISMN (-24.2% +/- 11% vs. -16.1% +/- 11%; P < 0.01). A reduction in HVPG of > 20% was significantly more frequent in the propranolol plus prazosin group than in the propranolol plus ISMN group (85% vs. 53%; P < 0.05). Neither treatment modified hepatic blood flow, quantitative liver function test results, glomerular filtration rate, plasma renin activity, or plasma aldosterone level. Side effects occurred in 13 patients receiving propranolol plus prazosin compared with 7 receiving propranolol plus ISMN (P = 0.16). CONCLUSIONS: Propranolol plus prazosin has a greater portal pressure-lowering effect than propranolol plus ISMN. Both therapies were safe for liver and renal function. However, the combination of propranolol plus prazosin caused a greater decrease in arterial pressure and was less well tolerated than propranolol plus ISMN.     

Osteoporosis after spinal cord injury

Immobilisation secondary to spinal cord injury (SCI) is associated with marked and rapid atrophy of trabecular bone. The purpose of this study was to evaluate bone mineral density (BMD) in both the upper and lower extremities following SCI sustained for various lengths of time and to correlate the BMD to the level of the lesion, time from injury, spasticity and serum calcium, phosphorus and alkaline phosphatase (ALP) levels. A study was undertaken in 41 SCI patients with a mean age of 35.8 +/- 12.7 years. A significant difference in BMD between upper and lower extremities of the paraplegics were found. BMD of upper and lower extremities were similar in tetraplegies. The BMD values were significantly different when the upper extremity scores of paraplegics and tetraplegics were compared but BMD scores of the lower extremities were similar in the two groups. The decrease in BMD was less in the spastic patients when compared to the flaccid group. There was a positive correlation between time from injury and the degree of BMD deficit in the paralysed areas. In the whole group of patients a significant positive correlation was found between the duration of SCI and serum ALP levels.     

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.     

Adjustment following spinal cord injury.

Investigated specific coping strategies associated with psychological adjustment following spinal cord injury with a battery of assessments administered to 57 patients (median age 26.5 yrs) participating in a spinal cord injury rehabilitation program. Ss were divided into 3 groups based on degree of psychological distress. High-distress Ss reported using more Wish-Fulfilling Fantasy, Emotional Expression, Self-Blame, and Threat Minimization Coping strategies relative to the low and moderate distress groups. The Self-Blame Coping strategy was significantly correlated with psychological distress over and above age, time since injury, or level of injury. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pain associated with spinal cord injury

Management of pain after spinal cord injury remains a difficult clinical problem. In particular, neuropathic spinal cord injury pain, like other forms of deafferentation pain in which there is loss or modification of normal afferent sensory inputs, is notoriously resistant to currently available modes of treatment. Although there have been some advances in our understanding of spinal cord injury pain, the mechanisms of neuropathic spinal cord injury pain remain largely unknown and treatment is often ineffective. This review presents findings from recent publications that deal with the mechanisms and management of spinal cord injury pain.     

Employment outcomes following spinal cord injury

PURPOSE: We determined the clinical utility of proton MR spectroscopy in defining the extent of disability in benign versus secondary-progressive multiple sclerosis (MS). METHODS: Thirty patients with clinically definite MS, including 16 patients with benign MS and 14 with secondary-progressive MS, and a group of 13 healthy volunteers were studied with combined stimulated-echo acquisition mode proton MR spectroscopy and MR imaging (all patients received contrast material). RESULTS: Acute enhancing lesions of benign and secondary-progressive MS were characterized by a reduction in N-acetylaspartate (NAA)/choline and NAA/creatine and an increase in inositol compounds/creatine as compared with normal white matter. Such variations were also detected in chronic unenhancing lesions in patients with secondary-progressive MS, although they were not found in chronic unenhancing lesions in patients with benign MS. Chronic lesions of the two forms of the disease have significative differences in NAA and inositol signals. CONCLUSION: Proton MR spectroscopy is able to show metabolic changes occurring in the white matter of patients with MS. Such changes differ according to the phase (acute versus chronic) and the clinical form (benign versus secondary-progressive) of the disease.     

Effects of drugs on walking after spinal cord injury

Clonidine, a noradrenergic agonist, and cyproheptadine, a serotonergic antagonist, have each been associated with improved walking in SCI subjects. Baclofen, a GABA agonist, is frequently prescribed for spasticity but its effects on walking have not been well quantified. The objective of this study was to compare the effects of clonidine, cyproheptadine and baclofen on walking in SCI subjects with incomplete injuries. A motorized treadmill was used and harness support provided when necessary. A repeated single-subject design was employed for the twelve subjects. The greatest effects were found in more severely disabled subjects. Cyproheptadine was associated with greatly reduced need for assistance, increases in maximum treadmill speed (MTS) and reduced clonus. Clonidine was associated with increases in MTS and a generally more upright posture. Baclofen was associated with minor changes in walking. In many cases of drug effects, MTS increases and other changes were retained following washout of drugs. The significance and implications of the drug effects and the retention of effects during washout periods are discussed. It is concluded that clonidine and cyproheptadine have different effects but both appear useful for severely disabled SCI subjects. The effects of baclofen on walking after spinal cord injury remains unclear.     

Effect of timing of stabilization on length of stay and medical complications following spinal cord injury

The disposition of intramuscular artemether (AM) was studied in 26 Kenyan children with cerebral malaria. Antimalarial activity determined by bioassay was compared with total plasma AM plus dihydroartemisinin (DHA) determined by high power liquid chromatography (HPLC). Therapeutic levels were achieved in most subjects (21/26) within 1 h of receiving intramuscular AM (3.2 mg/kg), with close correlation between bioassay and HPLC measurements (r = 0.706). However, there was marked inter-individual variation, antimalarial activity was undetectable in 5 subjects ('non-absorbers'), and plasma concentrations were lower in subject with respiratory distress. The 50% parasite clearance time was significantly longer in non-absorbers (mean = 13.1 h, SD = 10.8 vs. mean = 7.8 h, SD = 5.5; P = 0.013). We conclude that the bioavailability of intramuscular AM in children with severe malaria may be highly variable, particularly in the presence of respiratory distress, and may be associated with an inadequate therapeutic response.     

Cancer of the bladder in spinal cord injury patients

Since 1963, 10 cases of bladder carcinoma have been detected in 1,052 new admissions to our center. A high percentage of these patients had squamous cell carcinoma and/or squamous elements. This relatively high incidence stimulated a prospective study of 81 spinal cord injury patients either maintained on intraurethral catheter drainage for 10 years or an external appliance for 15 years. There were changes of squamous metaplasia in 19 per cent of the cases but no cancer was detected. It remains undetermined if squamous metaplasia is a pre-malignant lesion. However, the incidence of squamous metaplasia and squamous cell carcinoma in paraplegics with chronically infected bladders is not uncommon. Any spinal cord injury patient with hematuria needs a complete bladder evaluation and any long-term paraplegic with chronic infection should undergo cystoscopy and Papanicolaou smears as part of the yearly checkup.     

Aging and life adjustment after spinal cord injury

We studied the short-term effects of Paris winter air pollution (i.e., sulfur dioxide, Black Smoke, suspended particulates with an aerodynamic diameter close to 10 microm, and nitrogen dioxide) in 40 nonsmoking mild to moderate asthmatics (52% male; mean age = 46 y; 90% treated with inhaled steroids). During a 6-mo period, subjects recorded asthma symptoms and three daily peak expiratory flow measurements. Statistical analysis (i.e., generalized estimating equation models that accounted for autocorrelation of responses, weather data, and time trends) revealed consistent and significant associations between the pollutants and asthma attacks and symptoms in the entire study group, especially in the subgroup of individuals who took inhaled beta2 agonists as needed. Pollutants correlated negatively with morning peak expiratory flow in the subgroup that took inhaled beta2 agonists as needed, and they correlated positively with daily variability in asthmatics who received regularly scheduled inhaled beta2 agonists. The effects lingered several days after exposure occurred. Low-level pollution has consistent measurable effects on nonsmoking adults who have well-treated mild or moderate asthma.     

Apoptosis after traumatic human spinal cord injury

OBJECT: Apoptosis is a form of programmed cell death seen in a variety of developmental and disease states, including traumatic injuries. The main objective of this study was to determine whether apoptosis is observed after human spinal cord injury (SCI). The spatial and temporal expression of apoptotic cells as well as the nature of the cells involved in programmed cell death were also investigated. METHODS: The authors examined the spinal cords of 15 patients who died between 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, particularly in the ascending tracts, by using histological (cresyl violet, hematoxylin and eosin) and nuclear staining (Hoechst 33342). The presence of apoptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32), a member of the interleukin-1beta-converting enzyme/Caenorhabditis elegans D 3 (ICE/CED-3) family of proteases that plays an essential role in programmed cell death. Apoptosis in this series of human SCIs was a prominent pathological finding in 14 of the 15 spinal cords examined when compared with five uninjured control spinal cords. To determine the type of cells undergoing apoptosis, the authors immunostained specimens with a variety of antibodies, including glial fibrillary acidic protein, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPase and a number of apoptotic nuclei colocalized with positive staining for this antibody. CONCLUSIONS: These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of caspase-3 of the cysteine protease family. This mechanism of cell death contributes to the secondary injury processes seen after human SCI and may have important clinical implications for the further development of protease inhibitors to prevent programmed cell death.     

Bronchial hyperresponsiveness after cervical spinal cord injury

Cervical spinal cord injury results in interruption of sympathetic airway innervation, which originates from the upper thoracic spine, whereas parasympathetic nerve supply, arising in the vagal nuclei of the brainstem, remains intact. To assess the effect of such an altered neural environment on airway reactivity, bronchoprovocation testing was performed on eight subjects with nonacute traumatic lesions of the cervical spine, all of whom were lifetime nonsmokers without history of respiratory symptoms prior to their injury. Bronchial challenge was subsequently repeated after pretreatment with the anticholinergic agent, ipratropium bromide, an inhibitor of airway muscarinic receptors. All subjects demonstrated hyperresponsiveness to methacholine (the concentration of methacholine producing a fall in FEV1 of 20 percent from baseline [PC20] = 1.42 +/- 1.61 [SD] mg/ml). Airway hyperreactivity was completely blocked by pretreatment with inhaled ipratropium bromide (mean PC20 > 25 mg/ml [p < 0.0001]). The bronchial hyperresponsiveness observed in this population most likely reflects the loss of sympathetic airway innervation and resultant unopposed cholinergic bronchoconstrictor tone which results from transection of the cervical spine. Blockade of methacholine hyperresponsiveness with ipratropium bromide suggests a muscarinic receptor-mediated phenomenon.     

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.     

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.     

A crash course in spinal cord injury

The complex management issues related to spinal cord injury traditionally have been the purview of physical medicine and rehabilitation specialists. However, changes in the healthcare system now offer primary care physicians an expanded role in helping affected patients live a healthier and more functional life. With proper understanding of the mechanisms of spinal cord injury, primary care physicians can become important members of the medical management team. Dr Yu presents a comprehensive overview of medical care issues and common complications in spinal cord injury.     

Recovery in rats after spinal cord injury

Previous studies from this laboratory have shown evidence of regeneration of long descending spinal motor tracts in rats after spinal cord transection and treatment to modify the animals' immune response. In this study, less extensive surgical lesions were combined with the most favorable drug treatment (75 mg per kilogram of cyclophosphamide in a single dose) in an effort to improve the prospects for regeneration. Less than complete spinal cord transections in the rat were frequently followed by clinical and electrophysiologic evidence of return of function. Such return of function appears to depend on a reorganization of the nervous system that results in the use of the few remaining fibers to transmit motor information rather than on regeneration. Immunosuppressive treatment had no effect on these results.     

Effects of lecithinized superoxide dismutase on rat spinal cord injury

T cell interaction with antigenic peptides leads to signal transduction and activation events in the effector cells. Recent studies of T cell responses to subtle variants of antigenic peptides can lead to alterations in the activation state of T cells. A variety of physiological roles for altered peptide ligands have recently been postulated, and their potential therapeutic applications have generated considerable interest. This review summarizes progress made in understanding the T cell signal transduction pathways and the nature of T cell responses to altered peptide ligands. Our recent observation of a self peptide as a partial agonist for a cytotoxic T cell clone directed to a foreign antigen suggests that naturally occurring altered peptide ligands may be important in regulating T cell mediated immune response.     

Neuroprotection after spinal cord injury: state of the science

There have been no reports indicating diurnal variations in MRI at different portions of each lumbar disc. Eight asymptomatic healthy volunteers between 22 and 29 years old had MRI of their lumbar spine, twice on the same day (in the morning and evening). Forty lumbar discs were studied and the signal intensity change was measured from three portions of each disc (a total of 120 portions). No visible changes could be detected between scans by blinded observers. However, the calculated signal intensity changes showed an average loss of -20.0% (ant., 5 cases), -19.0% (mid, 2 cases), and -17.5% (post., 1 case). Height loss of the disc showed an average loss of -9.9% (ant., 4 cases), -8.3% (mid., 2 cases), and -10.4% (post., 2 cases). An increase of disc bulge at L4-5 level (18.3%) was pronounced, but L5-S1 level was less than others. Loss of body height averaged a loss of 7 mm (0.39% of body height). There was no correlation between reduced signal intensity and height loss at the ant./post. portion (p = 0.42), but there was a close relation at the mid. portion (p = 0.008). Diurnal change of the disc bulge was not correlated with reduced signal intensity (p = 0.48) or height loss (p = 0.16). Intradiscal fluid change was not necessarily influenced by the disc height loss, and height loss did not necessarily have an effect on disc bulge. But diurnal change showed a trend that was reflected in reduced signal intensity, height loss, and an increase of disc bulge which was more apparent from the ant. portion to the post, portion on moving down to the lower levels. Loss of disc height was one factor in the reduction of body height. These changes occurred randomly throughout 5 lumbar disc levels in each case.