Biomedical subjects

Shinichi Kikuchi

Publications and source records attributed to Shinichi Kikuchi.

At least 37 records · Page 2Linked to original sources

PubMed2004

Lumbar sympathectomy increases blood flow in a dog model of chronic cauda equina compression.

OBJECTIVE: This study was designed to assess changes in blood flow of the dog cauda equina after lumbar sympathectomy using an experimental chronic cauda compression model. METHODS: The cauda equina was compressed at 10 mm Hg with a plastic balloon in all animals (n = 12). One week later, bilateral lumbar sympathectomy was carried out in the LSX group (n = 7), and vessels of the cauda equina were thereafter observed for 90 minutes using a specially designed microscope supplied with a video camera. Five animals did not undergo sympathectomy and were used as controls. The volume of blood flow was calculated from two parameters: velocity (mm/s) and diameter (microm) of a vessel observed in each animal. RESULTS: The increment in vessel diameter in the LSX group was pronounced at 30 and 45 minutes after sympathectomy compared with the control group (P < 0.05). Blood flow in the LSX group was increased at 30 minutes depending on dilation of the vessel diameter compared with the control group (P < 0.05). The velocity in the observed vessels remained unchanged throughout the measurements. CONCLUSIONS: These data suggest that lumbar sympathectomy could induce an increase in blood flow of the compressed cauda equina. As lumbar sympathetic block increases blood flow not only in the lower limbs but also in the cauda equina, it might be evaluated for a conservative treatment of intermittent claudication due to lumbar spinal canal stenosis.

Animals↗

PubMed2004

Sustained MAPK activation is dependent on continual NGF receptor regeneration.

It still remains intriguing how signal specificity is achieved when different signals are relayed by the common intracellular signal transduction pathways. A well documented example for signal specificity determination is found in rat phaeochromocytoma PC12 cells where epidermal growth factor (EGF) stimulation produces a transient mitogen-activated protein kinase (MAPK) activation and leads to cell proliferation while nerve growth factor (NGF) initiates a sustained MAPK activation and induces cell differentiation. In this simulation, we demonstrated that NGF-induced sustained MAPK activation may mainly depend on continual regeneration of NGF receptors and that the presence of a small pool of surface receptors is enough to maintain a sustained MAPK activation. On the other hand, MAPK activation is not significantly sensitive to the half-life of internalized receptors and the levels of NGF-specific MAPK phosphatase MAP kinase phosphatase-3 (MKP-3), though cytoplasmic persistence of internalized NGF-bound receptors and the MKP-3 dependent feedback control also contribute to the sustaining of MAPK activation. These results are consistent with the recent experimental evidence that persistent tyrosine receptor kinase A (TrkA) activity is necessary to maintain transcription in the differentiating PC12 cells (Chang et al. 2003) and a sustained Src kinase activity is detected in response to NGF stimulation (Gatti 2003). It is suggested that sustained or transient MAPK activation induced by different growth factor and neurotrophins, which is crucial to their signaling specificity, could be satisfactorily accounted for by their specific receptor turnover kinetics rather than by the activation of specific downstream signaling cascades.

Animals↗

PubMed2004

Anatomic and clinical investigation of a low signal peripheral line (black line) around the lumbar herniated nucleus pulposus on magnetic resonance imaging.

It has been reported that a low signal peripheral line (black line) around the lumbar herniated nucleus pulposus (HNP) on magnetic resonance imaging (MRI) can be used for the evaluation of the interruption of the posterior longitudinal ligament (PLL). However, the previous reports have showed that different rates of agreement between MRI and surgical findings. In order to clarify this matter, the black line on MRI was assessed by a combined anatomic and clinical investigation. Three cadavers were used for the anatomic part of the study. For the clinical study, 11 patients with the diagnosis as HNP and 5 healthy volunteers were subjected to MRI to compare with the results from the anatomic study. The lumbo-sacral spine was dissected en bloc from the cadavers. The first imaging on MRI of the specimens was performed with the dural sac; the second imaging was performed after the dural sac and the nerve roots have been removed but with the PLL left; the third imaging was performed after the PLL was completely removed. After completion of imaging, the specimens were cut in sagittal and horizontal planes for histological evaluation. In the cadavers after removing the PLL histologically, the black lines were still shown on MRI. Finally, after changing encoding, the black lines were interrupted at some disc levels in the cadaver specimen, the patients with HNP, and healthy volunteers. Therefore the black lines could be interpreted as a chemical shift artifact. These results indicate that the continuity or the discontinuity of the black line is not appropriate sign to diagnose whether disruption of the PLL has occurred or not.

Adult↗

PubMed2004

Pathoanatomic investigation of cervical spondylotic myelopathy.

Multiple dural sac and spinal cord indentations are often observed on MRI in cervical spondylotic myelopathy. However, it is rare that all of the indented levels contribute to clinical symptoms. Pathological changes in cervical compression myelopathy have previously been reported. Still the critical degree of spinal cord compression needed to induce pathologic changes is unknown. To clearfy this matter the relationships between the spinal cord as well as the dural sac indentations, and pathological changes of the cervical spinal cord were investigated in cadavers. Sixty-eight cadavers were used for this study. The dural sac and the spinal cord were observed especially regarding presence of indentations. The spinal cord was removed from the specimens in order to perform histopathological examination. The indentations of the dural sac and the spinal cord were observed at C4/ 5, C5/6, C6/7 and C3/4 intervertebral levels in order of incidence. However, all of the dural sac indentations were not correlated with spinal cord indentations. Pathological changes in the spinal cord were observed in two specimens with less than 30% of the AP compression ratio. One specimen with 20.9% in the AP compression ratio had remarkable histopathological changes. In the other specimen with 29.6% in the AP compression ratio, diffuse demyelination was distributed in the lateral white matter. The results indicate that the critical degree of the AP compression ratio is 30% to induce histopathological changes in the spinal cord. If a spinal cord indentation in the patient with cervical spondylotic myelopathy on imaging, i.e. MRI, show less than 30% in the AP compression ratio, the clinical symptoms, i.e. numbness, tickling and paresthetic pain, may not be improved after the surgery because of some histopathological changes in the spinal cord.

Adult↗

PubMed2003

ISSLS prize winner: Erythropoietin inhibits spinal neuronal apoptosis and pain following nerve root crush.

STUDY DESIGN: The authors investigated the association of L5 proximal nerve root injury with spinal cord neuronal apoptosis (histologic) and whether exogenous erythropoietin therapy might reduce apoptosis/or pain (behavioral). OBJECTIVES: The first objective was to determine whether nerve root crush induces specific programmed cell death of spinal neurons in the dorsal and ventral horn and whether this is correlated with pain behaviors. The second objective was to determine if exogenous erythropoietin might reduce apoptosis and/or pain. SUMMARY OF BACKGROUND DATA: Whether spinal neuronal apoptosis is correlated with pain behaviors following nerve root injury remains unknown. It has been hypothesized that neuroprotective factors may alleviate pain behaviors by protecting neurons from death. Erythropoietin is a hematopoietic growth factor that recently has been demonstrated as a potent neuroprotective factor against ischemic damage in the brain. The effects of erythropoietin on pain and spinal cord neurons have not been examined. METHODS: Sprague-Dawley rats received a L5 proximal nerve root crush injury or sham operation and were separated into two treatment groups for subcutaneous injection: 1) vehicle; 2) recombinant human erythropoietin, 2680 U/kg. The rats were sacrificed, and spinal cords were removed for apoptotic and immunohistochemical analysis at 0, 1, and 3 days after surgery. To determine whether recombinant human erythropoietin prevented mechanical allodynia in animals with nerve root crushes (n = 12/group), both treatment groups were tested for pain behaviors using the von Frey test at -1, -2, -3, 1, 3, 7, 11, and 14 days after surgery. RESULTS: After nerve root injury, apoptotic neurons increased by 80% in the ipsilateral spinal cord and moderately in contralateral spinal cord in vehicle-treated animals compared to uninjured controls. Recombinant human erythropoietin reduced (P < 0.05) neuronal apoptosis in both superficial dorsal and ventral horns of the spinal cord. This corresponded with identification of erythropoietin and its receptors on spinal neurons and reductions in TNF-alpha colocalization in ventral horn neurons. Mechanical allodynia developed in the corresponding ipsilateral hind paw within 1 day and was sustained until day 14. Recombinant human erythropoietin-treated animals demonstrated faster recovery from mechanical allodynia compared with vehicle-treated controls (P < 0.05). CONCLUSIONS: Our findings indicated that L5 proximal nerve root crush increased neuronal apoptosis in the superficial dorsal and ventral horn that correlated with mechanical allodynia. Exogenous recombinant human erythropoietin facilitated receptor-mediated neuroprotection of spinal cord neurons and faster recovery from mechanical allodynia. Erythropoietin may be a potential therapeutic factor for patients with low back pain by providing pain relief and neuroprotection.

Animals↗

PubMed2003

Immunoreactivity of brain-derived neurotrophic factor in rat dorsal root ganglion and spinal cord dorsal horn following exposure to herniated nucleus pulposus.

The pain mechanisms underlying radiculopathy due to disc herniation are still incompletely understood. This study assessed changes in brain-derived neurotrophic factor (BDNF) expression, a modulator of nociceptive information, in the dorsal root ganglion (DRG) and spinal cord dorsal horn following experimental disc herniation. Immunohistochemical analysis revealed an increase in percentage of BDNF-immunoreactive (IR) neurons profiles in the affected DRG and marked elevation in the BDNF-IR regions within both the superficial and deep layers at the corresponding spinal level with a peak at 3 days after nucleus pulposus (NP) application. These results thus show that herniated NP increases the BDNF production in the pain-processing neurons. Such changes can contribute to the development of inflammatory hyperalgesia.

Animals↗

PubMed2003

Expression pattern of glypican-1 mRNA after brain injury in mice.

Glypican-1, a heparan sulfate proteoglycan, is expressed in various tissues including developing and postnatal central nervous system. It serves as a receptor for heparin-binding molecules such as fibroblast growth factors (FGFs). We investigated whether glypican-1 was expressed after brain injury in adult mice. In situ hybridization study showed that glypican-1 mRNA was expressed in the region surrounding necrotic tissue, and that the signal intensity peaked 7 days after the cryo-injury. In addition, both FGF-2 and amyloid precursor protein (APP) were concurrently upregulated and colocalized with glypican-1 mRNA. Since FGF-2 and APP can bind to glypican-1 in vitro, the present study suggested that their autocrine/paracrine interactions with glypican-1 may be involved in neuronal regeneration and/or neurite-outgrowth inhibition after brain injury.

Amyloid beta-Protein Precursor↗

PubMed2003

Effects of neutralizing antibodies to tumor necrosis factor-alpha on nucleus pulposus-induced abnormal nociresponses in rat dorsal horn neurons.

STUDY DESIGN: The effect of an anti-tumor necrosis factor alpha (anti-TNFalpha) antibody on abnormal discharges caused by application of nucleus pulposus to the nerve root was investigated in an electrophysiologic study. OBJECTIVES: To assess whether inhibition of TNFalpha can reduce nucleus pulposus-induced abnormal discharges. SUMMARY OF BACKGROUND DATA: It has been shown that TNFalpha, a proinflammatory cytokine, is a key pathogenic factor in the development of nucleus pulposus-induced abnormal discharges as a pain sensation. However, the electrophysiologic mechanisms involved in sciatica after disc herniation still have not been elucidated. METHODS: Extracellular activities of wide-dynamic-range neurons were assessed in 21 rats. Autologous nucleus pulposus harvested from the tail was applied to the L5 nerve root. The animals were simultaneously treated with antibodies to TNFalpha (anti-TNF + nucleus pulposus group) and with phosphate-buffered saline (nucleus pulposus group). As a control (control group), a similar volume of muscle was applied to the nerve root with phosphate-buffered saline. Responses of wide-dynamic-range neurons to noxious and innocuous stimuli were examined for 2 hours. RESULTS: Discharges evoked during noxious stimulation and discharges after withdrawal of stimulation in the nucleus pulposus group were significantly higher than those in the control group (P < 0.05). In the anti-TNF + nucleus pulposus group, discharges after withdrawal of stimulation were remarkably inhibited, as compared with those of the nucleus pulposus group (P < 0.05). However, evoked discharges during stimulation apparently were not inhibited. Responses to innocuous stimulation did not change throughout the measurements. CONCLUSIONS: These data indicate that application of TNFalpha antibodies to the nerve root partially prevents the nucleus pulposus-induced abnormal nociresponses. Therefore, anti-TNFalpha treatment may have a therapeutic effect on sciatica after lumbar disc herniation.

Animals↗

PubMed2003

Slit and glypican-1 mRNAs are coexpressed in the reactive astrocytes of the injured adult brain.

The slit family serves as a repellent for growing axons toward correct targets during neural development. A recent report describes slit mRNAs expressed in various brain regions in adult rats. However, their functions in the adult nervous system remain unknown. In the present study, we investigated whether slit mRNAs were expressed in the cryo-injured brain, using in situ hybridization. All slit family members were expressed at the lesion. Slit2 mRNA was the most intensely expressed in the cells surrounding the necrotic tissue. A double-labeling study showed that slit2 mRNA was expressed in the glial fibrillary acidic protein (GFAP)-positive reactive astrocytes. In addition, glypican-1, a heparan sulfate proteoglycan that serves as a high-affinity receptor for Slit protein, was coexpressed with slit2 mRNA in the reactive astrocytes. These findings suggested that slit2 might prevent regenerating axons from entering into the lesion in concert with glypican-1.

Animals↗

PubMed2003

Dynamic modeling of genetic networks using genetic algorithm and S-system.

MOTIVATION: The modeling of system dynamics of genetic networks, metabolic networks or signal transduction cascades from time-course data is formulated as a reverse-problem. Previous studies focused on the estimation of only network structures, and they were ineffective in inferring a network structure with feedback loops. We previously proposed a method to predict not only the network structure but also its dynamics using a Genetic Algorithm (GA) and an S-system formalism. However, it could predict only a small number of parameters and could rarely obtain essential structures. In this work, we propose a unified extension of the basic method. Notable improvements are as follows: (1) an additional term in its evaluation function that aims at eliminating futile parameters; (2) a crossover method called Simplex Crossover (SPX) to improve its optimization ability; and (3) a gradual optimization strategy to increase the number of predictable parameters. RESULTS: The proposed method is implemented as a C program called PEACE1 (Predictor by Evolutionary Algorithms and Canonical Equations 1). Its performance was compared with the basic method. The comparison showed that: (1) the convergence rate increased about 5-fold; (2) the optimization speed was raised about 1.5-fold; and (3) the number of predictable parameters was increased about 5-fold. Moreover, we successfully inferred the dynamics of a small genetic network constructed with 60 parameters for 5 network variables and feedback loops using only time-course data of gene expression.

Algorithms↗

PubMed2003

Pathomechanisms of nerve root injury caused by disc herniation: an experimental study of mechanical compression and chemical irritation.

STUDY DESIGN: An electrophysiologic and histologic study on nerve roots after mechanical compression and/or local application of nucleus pulposus (NP) was performed. OBJECTIVE: To assess the effects of mechanical compression and/or chemical irritation caused by NP. SUMMARY OF BACKGROUND DATA: It has been shown that application of NP to nerve roots without compression induces histologic and functional changes in nerve roots and the dorsal root ganglia. In clinical situations, however, mechanical compression has also been considered an important factor in disc herniation. METHODS: Eighteen dogs (9-15 kg) were used in this study. Four groups were used to assess the effect of each factor: 1) sham group (n = 3); 2) NP group (NP applied under the S1 lamina) (n = 5); 3) comp group (a plastic balloon placed under the S1 lamina) (n = 5); and 4) comp+NP group (a balloon and NP placed under the S1 lamina) (n = 5). Ascending cauda equina action potentials (CEAPs) and cauda equina-sensory nerve conduction velocity (SCV) were recorded before, immediately after, and 1 week after treatment. Histologic changes were also assessed by light microscopy. RESULTS: There were no significant differences in CEAP and SCV among the four groups immediately after the treatment. However, 1 week after treatment, the amplitudes in the NP group, comp group, and comp+NP group were statistically significantly lower compared with those in the sham group. The comp+NP group showed significantly lower amplitude than did the NP group and comp group. Immediately after treatment, SCV in the NP group and comp group did not show significant differences compared with that in the sham group. However, 1 week after treatment, SCV in the comp+NP group was significantly lower compared with that in the sham group. Histologic changes such as intraneural edema, Schwann cell edema, and nerve fiber injury seemed to be more pronounced in the comp+NP group than in the other groups. CONCLUSIONS: It was shown that each of the assessed factors induces nerve dysfunction. However, the combination of mechanical compression (mass effect of herniated NP) and chemical irritation (inflammation around nerve root) may induce more nerve root injury than each factor per se.

Animals↗

PubMed2003

A histologic and functional study on cauda equina adhesion induced by multiple level laminectomy.

STUDY DESIGN: A histologic and functional study on cauda equina adhesion induced by multiple-level laminectomy was performed using rats. OBJECTIVE: To assess the relation between the extent of laminectomy and histologic and functional changes of the cauda equina induced by laminectomy. SUMMARY OF BACKGROUND DATA: It has been demonstrated that laminectomies may induce cauda equina adhesion, transiently or permanently. However, the relation between the extent of laminectomy and histologic and functional changes of the cauda equina induced by laminectomy is still unclear. METHODS: Sprague-Dawley rats (250-300 g) were used. They were divided into four groups: no-laminectomy group (n = 5) and single, double, and triple level laminectomy groups (n = 20, respectively). At 24 hours and 1, 3, and 6 weeks after laminectomy, rats in each group were killed, and specimens were obtained from L4 to L6. The histologic changes were assessed using the classification of Yamagami. Walking durations on treadmill test and ascending spinal nerve-evoked potential were assessed in laminectomy groups before laminectomy, then weekly for 1 to 6 weeks after laminectomy. RESULTS: With the greater extent of laminectomy, the decrease in cauda equina adhesions was more delayed. There was no difference in walking durations and ascending spinal nerve-evoked potential between pre- and postlaminectomy. CONCLUSIONS: The extent of laminectomy was related to recovery time of induced cauda equina adhesion. However, a delay in recovery from cauda equina adhesion may not produce a recognizable delay in recovery from clinical symptoms.

Animals↗

PubMed2003

Validation of the Japanese version of the Roland-Morris Disability Questionnaire.

The study was designed to validate a translated, culturally adapted questionnaire. We examined the reliability, validity, and responsiveness of the Japanese version of the Roland-Morris Questionnaire (RDQ) when assessing disability in Japanese patients with low back pain. The RDQ is a reliable, validated scale used to measure disability caused by low back pain. However, no validated Japanese version of this questionnaire is available. A series of 214 outpatients with low back pain participated in this validation study. The patients were given the RDQ and the SF-36, and assessed their pain and global rating of health. Among them, 57 who were clinically stable were given the RDQ again 2 weeks later. The reliability was examined based on the test-retest method and internal consistency. Sufficient reliability was demonstrated with a Chronbach's. coefficient of 0.85, and the reproducibility for the 30 patients was r = 0.91. The principal component analysis showed unidimensionality. The RDQ score of the 133 patients was significantly improved after treatment. The Japanese version of the RDQ is a useful scale that is easy to use with reliability, validity, and responsiveness when assessing patients with low back pain.

Adult↗

PubMed2003

Kinetic simulation of signal transduction system in hippocampal long-term potentiation with dynamic modeling of protein phosphatase 2A.

We modeled and analyzed a signal transduction system of long-term potentiation (LTP) in hippocampal post-synapse. Bhalla and Iyengar [Science 283(1999) 381] have developed a hippocampal LTP model. In the conventional model, the concentration of protein phosphatase 2A (PP2A) was fixed. However, it was reported that dynamic inactivation of PP2A was essential for LTP [J. Neurochem. 74 (2000) 807]. We introduced a dynamic modeling of PP2A; inactivation (phosphorylation) of PP2A by calcium/calmodulin-dependent protein kinase II (CaMKII) in the presence of calcium/calmodulin, self-activation (autodephosphorylation) of PP2A, and inactivation (dephosphorylation) of CaMKII by PP2A. This model includes complex feedback loops; both CaMKII and PP2A are autoactivated, while they inactivate each other. Moreover, we proposed an analysis strategy for model validation by applying the results of sensitivity analysis. In our system, calcineurin (CaN) played an essential role, rather than the activation of protein kinase C (PKC) as documented in the conventional model. From results of the analysis of our model, we found the following robustness as characteristics of bistability in our model: (1). PP2A reactions against calcium ion (Ca(2+)) perturbation; (2). PP2A inactivation against PP2A increase; (3). protein phosphatase 1 (PP1) activation against PF2A increase; and (4). PP2A reactions against PP2A initial concentration. These properties facilitated LTP induction in our system. We showed that another mechanism could introduce bistable behavior by adding dynamic reactions of PP2A.

Animals↗

PubMed2003

Inhibition of p38 MAP kinase activity enhances axonal regeneration.

Tumor necrosis factor alpha (TNF)-induced cellular signaling through the p38 mitogen-activated protein kinase (p38 MAPK) pathway plays a critical role in Wallerian degeneration and subsequent regeneration, processes that depend on Schwann cell (SC) activity. TNF dose-dependently induces Schwann cell and macrophage activation in vivo and apoptosis in primary SC cultures in vitro, while inhibition of p38 MAPK is thought to block these cellular processes. We show with Western blots that after sciatic nerve crush injury, phosphorylated p38 (p-p38) MAPK is significantly increased (P < 0.01) in distal nerve segments. In tissue sections, p38 co-localized immunohistochemically with activated Schwann cells (GFAP) and to a lesser degree with macrophages (ED-1). In other experiments, animals were gavaged with Scios SD-169 (10 or 30 mg/kg) or excipient (PEG300) 1 day before and daily after crush injury to the sciatic nerve. SD-169 is a proprietary oral inhibitor of p38 MAPK activity. The rate of axonal regeneration was determined by the functional pinch test and was significantly increased in treated animals 8 days after crush injury (P < 0.05; 30 mg/kg dose). In SD-169-treated animals with nerve transection, nerve fibers regenerating through a silicone chamber were morphologically more mature than untreated nerves when observed 28 days after transection. TNF immunofluorescence of distal nerve segments after crush injury suggested that SD-169 reduced SC TNF protein. In support of these findings, SD-169 significantly reduced (P < 0.05) TNF-mediated primary SC death in culture experiments. We conclude that inhibition of p38 activity promotes axonal regeneration through interactions with SC signaling and TNF activity.

Animals↗

PubMed2003

Anatomic study of the axis for surgical planning of transarticular screw fixation.

Transarticular screw fixation has shown increased stability compared with other posterior stabilization techniques. However, there have been few reports on vertebral artery injury related to the screw insertion. The current study measured the parameters of the pedicle and vertebral artery groove of the axis and clarified the accuracy and safety of the transarticular screw fixation. Direct measurements were taken from 98 dry axis vertebrae. The width and height of the pedicle were measured. The mediolateral and anteroposterior dimensions of the vertebral artery groove also were measured. Forty-one percent had asymmetry. In 20% of the specimens, the pedicle was smaller than the diameter of the screw (3.5 mm). The pedicle of the axis has large anatomic variability and asymmetry. Some pedicles were not suitable for atlantoaxial transarticular screw fixation. The risks associated with screw fixation should be prevented by preoperative computed tomography with three-dimensional reconstruction. Screw trajectory reconstruction with coronal and sagittal reconstruction is useful to evaluate the pedicle width and height.

Atlanto-Axial Joint↗

PubMed2002

Quantifying the stress induced by distress in patients with lumbar disc herniation in terms of natural killer cell activity measurements: chromium release assay versus multiparameter flow cytometric assay.

STUDY DESIGN: A comparative study was conducted. OBJECTIVES: To attempt quantification of the stress in patients with lumbar disc herniation by measuring natural killer cell activity, and to evaluate the assay methodology. SUMMARY OF BACKGROUND DATA: Stressful events may have adverse effects on health. Distress in the patient with lumbar disc herniation also may be a stressful event. Previous findings have shown the activity of natural killer cells to be impaired in medical student volunteers and after bereavement or other stressful life events. However, the stress in patients with spinal disorders has not been evaluated. The standard assay for natural killer cell activity has been the chromium release assay. However, this assay requires the use of radioactive chromium. Flow cytometric assay is a nonradioactive method that analyzes the activated natural killer lymphocyte subsets: CD45+, CD56+, CD69+. METHODS: Peripheral blood lymphocytes were obtained from 20 patients with lumbar disc herniation (mean age, 30.8 years) and 20 healthy individuals (mean age, 38.9 years). Both chromium release assay and flow cytometric assay were performed for each patient. RESULTS: The mean natural killer cell activity in the patients (8.0% +/- 4.3%) was significantly lower than in the 20 healthy adult volunteers (12.6% +/- 4.5%). The mean natural killer cell activity in the healthy volunteers was 12.6% +/- 4.5% for the chromium release assay and 11.0% +/- 4.1% for the flow cytometric assay. The correlation (r = 0.77) of natural killer cell activity between the two methods was high. CONCLUSIONS: Natural killer cell activity in the patients with lumbar disc herniation was significantly lower than in healthy individuals, and the stress induced by pain and other distress may be present in patients with lumbar disc herniation. For measuring natural killer cell activity, flow cytometric assay is a reproducible assay, and it may be a viable alternative to the standard chromium release assay.

Adult↗

PubMed2002

Local application of disc-related cytokines on spinal nerve roots.

STUDY DESIGN: To analyze the effects of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma on cauda equina function and to define if any of these cytokines could induce nerve root dysfunction comparable with the situation with application of nucleus pulposus. SUMMARY OF BACKGROUND DATA: Proinflammatory cytokines derived from the intervertebral disc have been suggested to mediate the nucleus pulposus-induced nerve root injury following local application of nucleus pulposus. However, it is not known if such cytokines may induce similar injury if applied separately. METHODS: A total of 29 pigs were used. Nucleus pulposus was harvested from lumbar discs and applied to the sacrococcygeal cauda equina following laminectomy of the first coccygeal vertebra in seven pigs. Five pigs received 1.66 microg of tumor necrosis factor-alpha, five pigs received 0.85 microg of interleukin-1beta, and five pigs received 1.66 microg of interferon-gamma. Seven pigs received autologous fat for control. Nerve conduction velocity was studied by local electrical stimulation and recordings in the tail muscles 7 days after the application. RESULTS: Application of nucleus pulposus and fat induced similar effects as seen in previous studies, with normal nerve conduction velocity for fat and a significant reduction for nucleus pulposus. Application of both interleukin-1beta and IFN-gamma induced slight reductions of nerve conduction velocity compared with fat, but they were not statistically significant. Tumor necrosis factor-alpha, however, induced a reduction of the velocity that was even more pronounced than for nucleus pulposus. CONCLUSION: Based on previous observations and the data of the present study, one may conclude that tumor necrosis factor-alpha from nucleus pulposus cells seems to be intimately involved with the basic pathophysiologic events leading to both nerve root dysfunction and pain after local, epidural application of nucleus pulposus. One may therefore also suspect that pharmacologic inhibition of tumor necrosis factor-alpha may at least theoretically be considered in the clinical situation with disc herniation and sciatica.

Action Potentials↗