Biomedical subjects

Hisatoshi Baba

Publications and source records attributed to Hisatoshi Baba.

At least 19 recordsLinked to original sources

PubMed2006

Targeted retrograde transfection of adenovirus vector carrying brain-derived neurotrophic factor gene prevents loss of mouse (twy/twy) anterior horn neurons in vivo sustaining mechanical compression.

STUDY DESIGN: Immunohistochemical analysis after adenovirus (AdV)-mediated BDNF gene transfer in and around the area of mechanical compression in the cervical spinal cord of the hyperostotic mouse (twy/twy). OBJECTIVE: To investigate the neuroprotective effect of targeted AdV-BDNF gene transfection in the twy mouse with spontaneous chronic compression of the spinal cord motoneurons. SUMMARY OF BACKGROUND DATA: Several studies reported the neuroprotective effects of neurotrophins on injured spinal cord. However, no report has described the effect of targeted retrograde neurotrophic gene delivery on motoneuron survival in chronic compression lesions of the cervical spinal cord resembling lesions of myelopathy. METHODS: LacZ marker gene using adenoviral vector (AdV-LacZ) was used to evaluate retrograde delivery from the sternomastoid muscle in adult twy mice (16-week-old) and (control). Four weeks after the AdV-LacZ or AdV-BDNF injection, the compressed cervical spinal cord was removed en bloc for immunohistologic investigation of b-galactosidase activity and immunoreactivity and immunoblot analyses of BDNF. The number of anterior horn neurons was counted using Nissl, ChAT and AChE staining. RESULTS: Spinal accessory motoneurons between C1 and C3 segments were successfully transfected by AdV-LacZ in both twy and ICR mice after targeted intramuscular injection. Immunoreactivity to BDNF was significantly stronger in AdV-BDNF-gene transfected twy mice than in AdV-LacZ-gene transfected mice. At the cord level showing the maximum compression in AdV-BDNF-transfected twy mice, the number of anterior horn neurons was sinificantly higher in the topographic neuronal cell counting of Nissl-, ChAT-, and AChE-stained samples than in AdV-LacZ-injected twy mice. CONCLUSION: Targeted AdV-BDNF-gene delivery significantly increased Nissl-stained anterior horn neurons and enhanced cholinergic enzyme activities in the twy. Our results suggest that targeted retrograde AdV-BDNF-gene in vivo delivery may enhance neuronal survival even under chronic mechanical compression.

Adenoviridae↗

PubMed2006

Anterior versus posterior surgery for osteoporotic vertebral collapse with neurological deficit in the thoracolumbar spine.

Despite the increasing number of reports on surgical treatments for thoracolumbar osteoporotic vertebral collapse with neurological deficits, the choice of surgery remains controversial. In this retrospective study, we compared the outcomes of posterior and anterior surgeries for single-level osteoporotic vertebral collapse with neurological deficit in the thoracolumbar spine. Both posterior and anterior surgical approaches were performed with a consistent procedure for a single surgical indication at one institution. Twenty-four patients treated with posterior surgery and 28 patients treated with anterior surgery were followed-up over an average of 5 years after surgery. Radiographic results (kyphotic angle, bony fusion, and instrumentation failure), neurological improvement, and surgical complications were compared between the two groups. The average correction angle after surgery was larger in the posterior group than in the anterior group (P = 0.013), but not at final follow-up (P = 0.755). The average loss of correction was also higher in the posterior group than in the anterior group (P = 0.037). There was no significant difference in neurological outcomes between anterior and posterior approaches (P = 0.080). Two-way analysis of variance (ANOVA) showed that the neurological outcome was better in wedge type than in flat type vertebral collapse, regardless of the type of surgical approach (P = 0.0093). In wedge type vertebral collapse, neurological improvement tended to be greater after anterior than after posterior surgery. In four of six cases with instrumentation failure in the anterior group, a titanium cage subsided more than 5 mm but bony fusion was eventually achieved without causing neurological problems. In the posterior group, six cases experienced instrumentation failure during the postoperative course (two cases with screws loosened from pedicles and bodies, and one case with breakage of a screw neck). None of the patients developed instrumentation-related neurological problems. Two cases in each group developed pseudoarthrosis. In single-level osteoporotic vertebral collapse with neurological deficit, anterior surgery tended to improve neurological deficit in wedge type, but not in flat type collapse, compared with posterior surgery.

Aged↗

PubMed2006

A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.

Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the chi (2) test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P=0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.

Adolescent↗

PubMed2006

Microvascular system of anterior cruciate ligament in dogs.

This study was done to investigate the microvascular system of anterior cruciate ligament (ACL) using dogs. The objective was to study the microvascular architecture and the status of the barrier function of the capillary wall in the ACL by using microangiogram, scanning (SEM), and transmission electron microscopy (TEM). The vascular system in the ACL has been intensively studied by a number of researchers, using several microangiographic techniques in dogs, rabbits, and humans. However, most of these microangiographic studies had significant shortcomings, including the lack of three-dimensional observations and function of the blood-joint barrier in the ACL. In this study, the microstructure of the ACL was examined using microangiogram, SEM, and TEM. We investigated the vasculature of the ACL with SEM of vascular corrosion casts. In addition, we examined the status of the barrier function of the capillary wall in the ACL using the protein tracer horseradish peroxidase (HRP). Feeding vessels of the ligament were predominantly coming from the synovial-derived vessels originating from the synovium attached to the ligament near the tibial and femoral bone insertions of the ACL. The anterior cruciate ligament was surrounded by synovium, which had abundant vessels. The branches of these synovial vessels were penetrating into the ligament and making the intrinsic vascular network. It was also ascertained under SEM that the perivascular space around the intrinsic vessels were communicating through the intrinsic ligament fiber bundles and the mesh-like synovial membrane. The capillaries in the ACL were all of the continuous type under TEM. The protein tracer that was injected into the joint space passed through the synovial membrane and entered into the capillary lumen in the ACL, but the tracer that was injected intravenously did not appear in the perivascular space. The existence of a blood-ACL barrier does not necessarily imply the existence of an ACL-blood barrier. We think that the blood flow in the ACL is definitely affected by the status of joint fluid and these barriers of endothelium. The clinical relevance of the fine vascular anatomy of the ACL in trauma surgery is considered. This deserves further consideration.

Angiography↗

PubMed2006

Effects of disease severity on response to lateral wedged shoe insole for medial compartment knee osteoarthritis.

OBJECTIVE: To determine the effects of lateral wedged insoles on knee kinetics and kinematics during walking, according to radiographic severity of medial compartment knee osteoarthritis (OA). DESIGN: A prospective case control study of patients with medial compartment OA of the knee. SETTING: Gait analysis laboratory in a university hospital. PARTICIPANTS: Forty-six medial compartment knees with OA of 23 patients with bilateral disease and 38 knees of 19 age-matched healthy subjects as controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We measured the peak external adduction moment at the knee during the stance phase of gait and the first acceleration peak after heel strike at the lateral side of the femoral condyles. Kellgren and Lawrence grading system was used for radiographic assessment of OA severity. RESULTS: The mean value of peak external adduction moment of the knee was higher in OA knees than the control. Application of lateral wedged insoles significantly reduced the peak external adduction moment in Kellgren-Lawrence grades I and II knee OA patients. The first acceleration peak value after heel strike in these patients was relatively high compared with the control. Application of lateral wedged insoles significantly reduced the first acceleration peak in Kellgren-Lawrence grades I and II knee OA patients. CONCLUSIONS: The kinetic and kinematic effects of wearing of lateral wedged insoles were significant in Kellgren-Lawrence grades I and II knee OA. The results support the recommendation of use of lateral wedged insoles for patients with early and mild knee OA.

Aged↗

PubMed2006

Salvage operation for persistent low back pain and sciatica induced by percutaneous laser disc decompression performed at outside institution: correlation of magnetic resonance imaging and intraoperative and pathological findings.

OBJECTIVE: We identified several problems associated with percutaneous lumbar disc decompression (PLDD) based on a study of patients who required salvage operations for complications after undergoing PLDD at an outside institution. BACKGROUND DATA: PLDD has been performed as a new treatment for intervertebral disc herniation in recent years, and its safety and effectiveness are in the process of being established. Because the procedure is simple to perform under local anesthesia, inappropriate irradiation and application to patients for whom it is not indicated have sometimes resulted in a poor outcome and serious complications. METHODS: The patients comprised 10 with lumbar disc herniation and three with lumbar spondylolisthesis. We analyzed the magnetic resonance (MR) imaging and operative findings as well as the pathological features of surgically obtained disc specimens and studied their relationships with the clinical outcomes of the operations. RESULTS: Initial examination of all patients at our hospital showed that PLDD had no effect on low back pain or sciatica. In patients who showed MR signal changes in the end-plate, the pathological examination revealed extensive necrosis of cartilage and bone. During salvage operations, severe adhesion of herniated masses to nerve roots was often observed, with carbonized disc tissue surrounding the nerve roots and might have their nerve root injured thermally. CONCLUSION: PLDD is associated with significant risk of disc, end-plate, and nerve root injuries, contrary to the general belief that the procedure is minimally invasive. Our findings highlight the need for careful diagnosis and sufficient technical skill when selecting PLDD as a treatment option.

Adult↗

PubMed2006

Effect of compensation procedures for velocity on repeatability and variability of gait parameters in normal subjects.

UNLABELLED: OBJECTIVE To evaluate the effects of a mathematical procedure that adjusts for gait velocity on the variability seen in gait analysis. DESIGN: Evaluation before and after compensation. SETTING: Gait laboratory, Fukui University Hospital, Japan. SUBJECTS: Fourteen normal volunteers. OUTCOME MEASURES: A computerized gait analysis system with two forceplates and a light source spot measuring device was used. Gait measurement in each subject was performed on three different days. RESULTS: The gait parameters measured on three different days were significantly different, particularly step length, stride length, velocity, the components of floor-reaction forces and hip motion. In these parameters, intraclass correlation coefficient, ICC (1,1) was not high (range 0.05-0.71). However, there was a high correlation between these parameters and velocity and high repeatability was obtained following compensation for velocity (ICC (1,1), range 0.73-0.97). In contrast, compensation of parameters whose measurement was not significantly different before compensation did not improve ICC (1,1). Variability of all parameters was acceptable, however CV (an index of variability) improved significantly after compensation compared with that before compensation in six of 15 parameters. CONCLUSIONS: Our findings suggest that low repeatability in gait parameters should be considered even when the gait of normal subjects is measured on different days. A high repeatability and more acceptable variability were obtained when the data were compensated for velocity.

Analysis of Variance↗

PubMed2006

Anterior expandable strut cage replacement for osteoporotic thoracolumbar vertebral collapse.

OBJECT: The authors investigated the usefulness of using an expandable cage strut in anterior reconstruction after osteoporotic vertebral collapse in patients with neurological deficits. METHODS: Twenty-eight patients who had undergone expandable cage strut-augmented anterior thoracolumbar reconstruction participated in a follow-up review for a mean of 4.9 years. Radiographs were reviewed for kyphosis, lateral tilt of the implant, cage subsidence, the presence of a solid fusion mass, and instrumentation failure. Changes in neurological status and visual analog scale (VAS) pain score, as well as technique-related complications, were examined. The mean angles +/- the standard deviations of kyphosis correction 4 to 6 weeks after surgery and at final follow-up examination were 10.4 +/- 7.6 degrees and 5.6 +/- 6.0 degrees, respectively. The mean subsidence of the expandable cage within the adjacent vertebrae was 2.5 +/- 3.0 mm at the final follow-up examination. Neurological improvement at the final follow up was more significant in patients with Type I (wedge-type) than Type 2 (flat-type) (p = 0.037) or Type 3 (concave-type) (p = 0.006) vertebral collapse. Follow-up VAS scores were significantly higher in patients with Type 1 than Type 3 collapse (p = 0.012). In all cases the authors observed solid union with incorporation of the cage. There were no surgery-related complications. CONCLUSIONS: An expandable titanium cage strut seems useful in vertebral body replacement in patients with osteoporotic thoracolumbar collapse. Favorable results were obtained in cases of Type I collapse (wedge type) in which the middle and posterior columns remained comparatively intact.

Aged↗

PubMed2005

Targeted retrograde gene delivery into the injured cervical spinal cord using recombinant adenovirus vector.

Direct routes of gene administration (intrathecal, intracerebroventricular or intraparenchymal infusion) have been used for effective and sustained gene delivery, but serious concerns exist about possible traumatic injury as well as neural damage that may lead to further tissue necrosis, apoptosis and cell death. We evaluated targeted retrograde gene delivery through the sternomastoid muscle (innervated by the spinal accessory nerves) into the injured cervical spinal cord using a recombinant adenovirus vector. LacZ gene expression in the cervical spinal cord was noted from 3 days to 4 weeks after the injection of vector into the sternomastoid muscles of the rats. Recombinant adenovirus vector was transferred via a retrograde mechanism into the injured cervical spinal cord with high transduction efficacy (80.6--98.9%) over certain adenoviral titer and dosage. Transduction was less efficient when the vector was injected 1 and 2 weeks after spinal cord injury (44.2--56.8%). Our results indicate retrograde delivery of recombinant adenovirus vector is possible immediately after spinal cord injury, and that this method is promising for gene delivery because it is effective, selective, less invasive to the injured spinal cord, has long-lasting gene expression, and is potentially feasible treatment choice for spinal cord injury.

Adenoviridae↗

PubMed2005

Effect of mechanical compression on the lumbar nerve root: localization and changes of intraradicular inflammatory cytokines, nitric oxide, and cyclooxygenase.

STUDY DESIGN: Investigation of intraradicular inflammation induced by mechanical compression. OBJECTIVE: To investigate the mechanism of nerve root pain, this study used a lumbar nerve root compression model. SUMMARY OF BACKGROUND DATA: The manifestation of pain at sites of inflammation has a close relationship with the release of mediators from macrophages. However, the mediators involved in inflammation of nerve roots as a result of mechanical compression remain almost unknown. METHODS: In this study, the seventh lumbar nerve root of dogs was compressed with a clip for 3 weeks to observe the changes caused by compression. Immunohistochemistry was performed using the avidin-biotin-peroxidase complex method to observe the changes of T cells (CD45) and macrophages (Mac-1) after compression. Antibodies against as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (i-NOS), and cyclooxygenase (COX)-1 and 2 were used to examine the localization and changes of these mediators caused by nerve root compression. RESULTS: In control animals, resident T cells were detected, but there were no macrophages. IL-1beta and COX-2 were positive in the Schwann cells and vascular endothelial cells, while COX-1 was detected in the vascular endothelial cells. However, no cells showed TNF-alpha or i-NOS positively. After nerve root compression, numerous T cells and macrophages appeared among the demyelinized nerve fibers. The macrophages were positive for IL-1beta, TNF-alpha, i-NOS, and COX-2. CONCLUSION: Inflammatory cytokines, NO, and COX-2 may be deeply involved in radiculitis caused by mechanical compression, and these mediators seem to be important in the manifestation of root pain.

Animals↗

PubMed2005

Localization and changes of intraneural inflammatory cytokines and inducible-nitric oxide induced by mechanical compression.

STUDY DESIGN: Investigation of intraneural inflammation induced by mechanical compression. OBJECTIVES: In order to investigate the mechanism of neuropathy, this study used a median nerve compression model in dogs. Immunohistochemistry was used to examine the localization and changes of inflammatory cytokines and nitric oxide (NO). SUMMARY OF BACKGROUND DATA: The manifestation of pain at sites of inflammation has a close relationship with the release of mediators from macrophages such as interleulin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), as well as with NO. However, the mediators involved in inflammation of nerve due to mechanical compression remain almost unknown. METHODS: In this study, the median nerve of dogs was compressed with a clip for three weeks to observe the changes caused by compression. Immunohistochemistry was done by the avidin-biotin-peroxidase complex method to observe the changes of T cells (CD45) and macrophages (Mac-1) after compression. Antibodies against IL-1beta, TNF-alpha, and inducible nitric oxide synthesis (i-NOS) were used to examine the localization and changes of these mediators caused by nerve compression. RESULTS: In control animals, resident T cells were detected, but there were no macrophages. IL-1beta was positive in the Schwann cells and vascular endothelial cells. However, no cells showed TNF-alpha or i-NOS positively. After nerve compression, numerous T cells and macrophages appeared among the demyelinized nerve fibers. The macrophages were positive for IL-1beta, TNF-alpha and i-NOS. CONCLUSION: Inflammatory cytokines and NO may be involved in intraneural inflammatory changes arising from mechanical compression. Such mediators may be of importance in the manifestation of neuropathy.

Animals↗

PubMed2005

Effect of lumbar nerve root compression on primary sensory neurons and their central branches: changes in the nociceptive neuropeptides substance P and somatostatin.

STUDY DESIGN: This study examined the effect of lumbar nerve root compression on nociceptive neuropeptides in the axonal flow using an in vivo model. OBJECTIVES: The aim was to investigate changes in axonal flow after nerve root compression by using immunohistochemical techniques to detect substance P (SP) and somatostatin (SOM), which is thought to be involved in temperature and pain sensation. SUMMARY OF BACKGROUND DATA: Disturbance of intraradicular blood flow and nerve fiber deformation caused by mechanical compression are thought to be involved in the pathophysiology of diseases characterized by radicular symptoms, such as lumbar disc herniation and lumbar canal stenosis. However, little research has been conducted into the changes of axonal flow associated with nerve root compression. METHODS: In dogs, the lumbar nerve roots were compressed using four types of clips with different pressures. Changes of SP and SOM levels in the spinal dorsal horn, dorsal root, and dorsal root ganglions were examined immunohistochemically after compression for 24 hours or 1 week. RESULTS: After compression for 24 hours, axonal flow in the dorsal root was impaired, accumulation of SP and SOM was observed distal to the site of compression, and there was a decrease in the number of dorsal root ganglion cells showing positively for these neurotransmitters. Compression for 1 week resulted in a decrease in the number of SP- and SOM-positive fibers in the spinal dorsal horn. CONCLUSION: Change of axonal flow resulting from direct nerve compression could affect the metabolism of neurotransmitters that flow inside the axons and may be a primary cause of the decline in nerve function.

Animals↗

PubMed2005

Multivariate analysis of the neurological outcome of surgery for cervical compressive myelopathy.

BACKGROUND: The neurological outcome of decompressive surgery for cervical myelopathy is influenced by several factors. Although each factor may have an independent effect, it is more likely that the outcome is influenced by more than one factor. We examined the results of multivariate analysis and multiple regression analysis of the neurological outcome of patients treated by cervical cord decompression. METHODS: A total of 77 patients with cervical spondylotic myelopathy (43 men, 34 women) and 58 with ossification of the posterior longitudinal ligament (OPLL) (39 men, 19 women) were studied with an average follow-up interval of 8.3 years. The clinical data, neurological and radiological findings, and results of spinal cord evoked potentials (SCEPs) were retrieved from the medical records and included in the analysis. RESULTS: Multivariate analysis indicated that the outcome for patients with spondylosis was positively influenced, in order of importance, by increased transverse area of the cord >or=60%, presence of single-level anterior fusion, a high preoperative neurological score, normal epidural SCEPs, and clinical features of brachialgia and cord type. In patients with OPLL, multivariate analysis showed that the long-term outcome was positively influenced, in order of importance, by the presence of mixed or localized OPLL, normal epidural SCEPs, high preoperative neurological score, a single-vertebra spondylectomy with anterior fusion, laminoplasty, widening of the transverse area of the cord >or=40%, and an expansion rate of the spinal canal after laminoplasty >or=40%. CONCLUSIONS: We suggest that multivariate analysis is useful for assessing the neurosurgical outcome in patients with cervical compressive myelopathy.

Adult↗

PubMed2005

Changes of calcitonin gene-related peptide in primary sensory neurons and their central branch after nerve root compression of the dog.

OBJECTIVE: To investigate changes in axonal flow after nerve root compression by using immunohistochemical techniques to detect calcitonin gene-related peptide (CGRP), which is thought to be involved in pain sensation. DESIGN: Experimental, controlled study. SETTING: University medical school in Japan. ANIMALS: Forty adult mongrel dogs (weight, 7-15kg). INTERVENTIONS: In dogs, the lumbar nerve roots were compressed using 4 types of clips with different pressures. Changes of CGRP levels in the spinal dorsal horn, dorsal root, and dorsal root ganglia (DRG) were examined immunohistochemically after compression for 24 hours or for 1 week. MAIN OUTCOME MEASURES: CGRP-positive neurons and CGRP-positive fibers. RESULTS: After compression, axonal flow in the dorsal root was impaired, accumulation of CGRP was observed distal to the site of compression, and the number of DRG cells showing positively for CGRP decreased. Compression for 1 week resulted in a decrease in the number of CGRP-positive fibers in the spinal dorsal horn. CONCLUSIONS: These findings indicate that CGRP dynamics are modified by nerve compression.

Animals↗

PubMed2005

Dynamic analysis of the resultant force acting on the hip joint during level walking.

The present study was designed to determine the resultant force acting on the hip joint during walking using a new dynamic analysis method. Our model utilized joint motion, ground reaction force, and muscle strength data from 18 women (6 normal women aged 20-24 years, 6 normal women aged 50-57 years, and 6 female patients with osteoarthritis, aged 50-66 years). We analyzed the resultant force using the multibody dynamic analysis system. To determine the factors that influence the force acting on the hip, we examined the effect of age and total hip arthroplasty. The maximum resultant force acting on the femoral head was dependent on the subject body weight and correlated with muscle strength and walking speed. The results of this study highlight the agreement between computer simulation analysis and actual measurement of the resultant force acting on the hip. Our results suggest that muscle strength and walking speed are significant determinants of the resultant force acting on the hip.

Adult↗

PubMed2005

[Blood circulation of cauda equina and nerve root].

It is generally considered that the genesis of radiculopathy associated with pathologic conditions of the spine, such as lumbar disc herniaton and lumbarl canal stenosis, may result from both mechanical compression and vascular problems. In this article, we have reviewed about the blood circulation of cauda equina and nerve root under normal and pathologic conditions.

Adult↗

PubMed2005

Imaging of intraneural edema by using gadolinium-enhanced MR imaging: experimental compression injury.

BACKGROUND AND PURPOSE: Compressive and entrapment neuropathies are diseases frequently observed on routine clinical examination. A definitive diagnosis based on clinical symptoms and neurologic findings alone is difficult in many cases, however, and electrophysiologic measurement is used as a supplementary diagnostic method. In this study, we examined to use protein tracers (Evans blue albumin or horseradish peroxidase) and gadolinium-enhanced MR imaging to determine the changes of blood-nerve barrier permeability in compressive neuropathies. METHODS: In dogs, the median nerve was compressed for 1 hour by using five kinds of clips with various strengths (7.5-90-g force). After clip removal, the combined tracers of Evans blue albumin and gadolinium or horseradish peroxidase was administered intravenously as a tracer. After the animals were euthenized, we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve under fluorescence microscopy. The horseradish peroxidase-injected specimens were observed by transmission electron microscopy. RESULTS: On enhanced MR imaging, intraneural enhancement was caused by 60- and 90-g-force compression after 1 hour. Marked extravasation of protein tracers in the nerve occurred where there was compression by 60- and 90-g-force compression, and capillaries in the nerve showed the opening of tight junction and an increase of vesicular transport under the electron microscopy. This situation indicated breakdown of the blood-nerve barrier, with consequent edema formation and was seen as enhancement on MR imaging. CONCLUSION: Gadolinium-enhanced MR imaging can detect morphologic and functional changes of blood-nerve barrier in the nerve induced by mechanical compression.

Animals↗

PubMed2004

Netrin-1 is crucial for the establishment of the dorsal column-medial lemniscal system.

The dorsal column-medial lemniscal system is a significant sensory pathway that mediates touch and limb position sense. In this system, axons from the second-order neurons in the dorsal column nuclei form the internal arcuate fibers, cross the ventral midline (floor plate) within the medulla oblongata, and then project to the thalamus as the medial lemniscus. Here we demonstrate that Netrin-1, which is secreted from the floor plate in the medulla oblongata, is indispensable to the formation of the dorsal column-medial lemniscal system. Axons from the dorsal column nuclei cross the midline at around embryonic day 11 in mice. Concurrently, Netrin-1 mRNA and its receptor DCC (deleted in colorectal cancer) were expressed in the floor plate and commissural axons there, respectively. In our explant culture experiments, the floor plates of the embryonic 11-day-old mutant Netrin-1 homozygous mice did not attract axons from the dorsal column nuclei of ICR mice, while those from the wild type littermates did. Moreover, we observed that although the dorsal column nuclei developed in situ in mutant mice, their axons were not attracted toward the floor plate: they did not cross midline and remained ipsilaterally, without forming the internal arcuate fibers, in embryonic 17-day-old mutant Netrin-1 homozygous mice.

Afferent Pathways↗