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Biomedical subjects

Y Kotani

Publications and source records attributed to Y Kotani.

At least 37 records · Page 2Linked to original sources

Platelet-activating factor increases the expression of metalloproteinase-9 in human bronchial epithelial cells.

Platelet-activating factor (PAF) plays an important role in the pathogenesis of bronchial asthma. To investigate the role of PAF in the maintenance and remodeling of the extracellular matrix, we evaluated the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 from human bronchial epithelial cells after PAF treatment. Gelatin zymography of human bronchial epithelial cell-conditioned media showed major pro-matrix metalloproteinase-9 and minor pro-matrix metalloproteinase-2 expression and these expressions were totally inhibited by the metalloproteinase inhibitor EDTA. The identification of matrix metalloproteinase-9 was confirmed by Western blot analysis. Northern blotting and zymography demonstrated that PAF induced the mRNA of matrix metalloproteinase-9 from human bronchial epithelial cells and an increase in the gelatinolytic activity of pro-matrix metalloproteinase-9 but not in that of pro-matrix metalloproteinase-2. Lyso-PAF did not induce matrix metalloproteinase-9 mRNA or the gelatinolytic activity of pro-matrix metalloproteinase-9. CV6209, an receptor antagonist of PAF, reduced the increases of pro-matrix metalloproteinase-9 mRNA and gelatinolytic activity induced by PAF. Another receptor antagonist of PAF, hexanolamine PAF, did not inhibit the increases in the synthesis or release of pro-matrix metalloproteinase induced by PAF. Based on these results, we propose that matrix metalloproteinase-9 may be actively involved in the PAF-induced physiopathological remodeling in human bronchial epithelial cells.

Bronchi↗

The effect of stimulus discriminability on stimulus-preceding negativities prior to instructive and feedback stimuli.

Stimulus-preceding negativity (SPN) was recorded in time estimation tasks that allowed the pre-instruction SPN and the pre-feedback SPN to be compared. In the task in which an acoustic tone was presented 3 s after a voluntary movement, (a) the level of stimulus discriminability (easy and difficult), and (b) the information content of the acoustic tone (feedback and instruction) were manipulated. The pre-instruction SPN over the right hemisphere tended to be larger under the difficult than under the easy level of discriminability, but the difference was only marginally significant. In contrast, the pre-feedback SPN over the right hemisphere was significantly larger under the easy than under the difficult level of discriminability. These findings suggest that the level of stimulus discriminability influences the pre-instruction and the pre-feedback SPN differently, and that it is probable that the pre-feedback and the pre-instruction SPN do not have the same functional significance.

Adult↗

Beta2-adrenergic receptor polymorphisms affect airway responsiveness to salbutamol in asthmatics.

We examined the beta2-adrenergic receptor (beta2AR) polymorphisms (Arg16-->Gly, Gln27-->Glu) and clinical status for 117 asthmatics. Airway responsiveness to methacholine and beta2-agonists was evaluated with Astograph. The atopic factors, pulmonary function test, and airway responsiveness to methacholine did not differ significantly among the different beta2AR genotypes. Asthmatics homozygous for Gly16 showed significantly lower airway responsiveness to inhaled salbutamol than those heterozygous for Arg/Gly16 or homozygous for Arg16. Asthmatics heterozygous for Gln/Glu27 had significantly later asthma onsets than those homozygous for Gln27. These results suggest that beta2AR polymorphisms play an important role in the airway responsiveness to inhaled beta2-agonist and the initial asthma onset.

Adolescent↗

The role of anteromedial foraminotomy and the uncovertebral joints in the stability of the cervical spine. A biomechanical study.

STUDY DESIGN: The biomechanical role of the cervical uncovertebral joint was investigated using human cadaveric spines. Sequential resection of cervical uncovertebral joints, including clinical anteromedial foraminotomy, was conducted, followed by biomechanical testing after each stage of resection. OBJECTIVES: To clarify the biomechanical role of uncovertebral joints and clinical anteromedial foraminotomy in the cervical spine and their effects on interbody bone graft stability. SUMMARY OF BACKGROUND DATA: Although the biomechanical role of the cervical uncovertebral joints has been considered to be that of a guiding mechanism in flexion and extension and a limiting mechanism in posterior translation and lateral bending, there have been no studies quantifying this role. According to results in quantitative anatomic studies, anatomic variations exist in uncovertebral joints, depending on the vertebral level, articular angulation, and relative height of the joints. METHODS: Fourteen human functional spinal units at C3-C4 and C6-C7 underwent sequential uncovertebral joint resection, with each stage of resection followed by biomechanical testing. The uncovertebral joint was divided anatomically into three parts on each side: the posterior foraminal part, the posterior half, and the anterior half. The loading modes included torsion, flexion, extension, and lateral bending. A simulated anterior bone graft construct was also tested after each uncovertebral joint resection procedure. RESULTS: Significant changes in stability were observed after sequential uncovertebral joint resection in all loading modes (P < 0.05). The biomechanical contribution of uncovertebral joints decreased in the following order: the posterior foraminal part, the posterior half, and the anterior half. Unilateral and bilateral foraminotomy most affected the stability of the functional spinal unit during extension, causing a 30% and 36% decrease in stiffness of the functional spinal unit, respectively. The effect was less in torsion and lateral bending. After sequential resection, there was a statistically significant difference between decreases in torsional stiffness at C3-C4 and C6-C7 (P < 0.05). The stiffness of the simulated bone graft construct decreased progressively during flexion and lateral bending after each foraminotomy (P < 0.05). Increased bone graft height of 79% returned stability to the preforaminotomy level. CONCLUSIONS: This is the first study to quantitate the biomechanical role of uncovertebral joints in cervical segmental stability and the effect at each intervertebral level. The effect differs because of anatomic variations in uncovertebral joints. The major biomechanical function of uncovertebral joints includes the regulation of extension and lateral bending motion, followed by torsion, which is mainly provided by the posterior uncovertebral joints. This study highlights the clinical assessment of additional segmental instability attributed to destruction of the uncovertebral joints during surgical procedures or by neoplastic lesions.

Biomechanical Phenomena↗

Video-assisted thoracoscopic surgery versus open thoracotomy for anterior thoracic spinal fusion. A comparative radiographic, biomechanical, and histologic analysis in a sheep model.

STUDY DESIGN: In this in vivo investigation, a sheep model was used to compare the efficacy of a video-assisted thoracoscopic approach and a traditional thoracotomy in promoting a successful interbody spinal arthrodesis. OBJECTIVES: To compare the incidence of successful anterior spinal arthrodesis among three stabilization techniques-iliac crest, Bagby and Kuslich device, and Z-plate--performed using a video-assisted thoracoscopic approach and conventional open thoracotomy approaches. SUMMARY OF BACKGROUND DATA: A clinical outcome study on open versus endoscopic spinal fusion is not yet available. Moreover, no basic scientific investigations have been conducted to determine whether the success of an endoscopic arthrodesis is comparable to that of a conventional open procedure. METHODS: Fourteen Western Crossbred sheep underwent three identical destabilization procedures at T5-T6, T7-T8, and T9-T10, in which the anterior and middle osteoligamentous columns of the spine were resected, followed by three randomized reconstruction procedures using iliac autograft alone, and Z-plate stabilization with iliac autograft. In seven sheep, the entire destabilization-reconstruction procedure was performed using a video-assisted thoracoscopic surgical approach. In the remaining seven, the procedure was performed by conventional open thoracotomy. RESULTS: Histomorphometric and biomechanical evaluation demonstrated that the video-assisted thoracoscopic approach and open thoracotomy arthrodesis had comparable bone formation and biomechanical properties (P > 0.05). However, the Z-plate fusions, as a group, demonstrated increased flexion-extension stiffness properties and trabecular bone formation compared with the autograft and Bagby and Kuslich device fusions (P < 0.05). CONCLUSIONS: Thoracic interbody spinal fusions performed by thoracoscopy have demonstrated histologic, biomechanical, and radiographic equivalence to those performed by a thoracotomy approach. However, in the endoscopy group, intraoperative complications causing longer operative times, higher estimated blood loss, and increased animal morbidity indicated a substantial learning curve associated with the adoption of this surgical technique.

Analysis of Variance↗

The effects of spinal fixation and destabilization on the biomechanical and histologic properties of spinal ligaments. An in vivo study.

STUDY DESIGN: An animal study was conducted to assess whether different surgical procedures of spinal fixation and destabilization would influence the biomechanics and histology of lumbar spinal ligaments. OBJECTIVES: To investigate the effects of spinal fixation and destabilization as well as surgical intervention itself on the biomechanical and histologic properties of lumbar spinal ligaments. SUMMARY OF BACKGROUND DATA: Although several investigators have reported normal biomechanical properties of different spinal ligaments, there have been no studies in which changes in spinal ligament properties, secondary to the altered biomechanical environment provided by such surgical procedures as spinal fixation and destabilization, have been investigated. METHODS: Thirty-six mature sheep were divided into four groups: Group I: nonsurgical control: Group II: sham operation consisting of bilateral posterolateral exposure at L4-L5; Group III: spinal fixation using transpedicular screws and plates and bilateral posterolateral bone graft at L4-L5; and Group IV: spinal destabilization consisting of bilateral facetectomy and anterior discectomy at L4-L5. Four months after surgery, the biomechanical analysis included destructive tensile testing of four different bone-ligament-bone complexes at the operative and proximal adjacent levels: anterior longitudinal ligament, posterior longitudinal ligament, ligamentum flavum, and supraspinous and interspinous ligaments combined. Histomorphometric analyses of the vertebral body and spinal ligaments were performed histomorphometrically. RESULTS: Biomechanical analysis results demonstrated remarkable changes in the structural and mechanical ligament properties at the operative level. The fixation group's ligaments showed consistent decreases in the ultimate load and elastic modulus compared with those parameters in the control group (P < 0.05). Histologically, the fixation group's ligamentum flavum showed marked vacuolation in the ligament substance, whereas the interspinous ligament exhibited significant insertion changes compared with little change in substance. In all eight sheep in Group IV, unintentional bilateral facet fusions were obtained; and in all eight animals in Group III with pedicle instrumentation and posterolateral fusion, solid arthrodesis was exhibited. This allowed a distinction to be made between the stress-shielding effect of spinal instrumentation and arthrodesis (Group III) versus spinal fusion alone (Group IV) on both spinal ligament and vertebral body. Group II (sham) had a significant decrease in supraspinous and interspinous ligaments, but nonsignificant decreases in the stress-shielding effect of 10-12% in other ligaments. CONCLUSIONS: Posterior spinal instrumentation and fusion led to decreased biomechanical properties of the ligamentum flavum, posterior longitudinal ligament, and interspinous and supraspinous ligaments. The stress-shielding effects were ligament dependent and were most pronounced on the posterior side. The altered biomechanical environment produced by spinal fixation, surgical intervention itself, or nonphysiologic mobilization can affect the ligamentous properties in vivo, possibly serving as the impetus for low back pain.

Animals↗

Clinical significance of plasma vascular endothelial growth factor in gastrointestinal cancer.

Circulating vascular endothelial growth factor (VEGF) was measured in gastric and colorectal cancer patients using an enzyme-linked immunosorbent assay (ELISA). Firstly, serum and plasma samples were collected from 20 normal controls to compare the values of VEGF and to determine which specimen type was most suitable for detecting circulating VEGF. Seventeen of 20 normal controls had plasma VEGF levels under the limit of detection (15 pg/ml) and the levels of the remaining three controls were 21, 22 and 38 pg/ml. In contrast, all serum samples indicated high levels of VEGF (mean 238 pg/ml), ranging from 44 to 450 pg/ml. In a time-course test of two normal controls serum VEGF values increased markedly between 30 and 60 min and remained high, whilst plasma VEGF values were low up to 480 min. Thus, plasma samples are more suitable for the measurement of circulating VEGF. Next, plasma VEGF levels were examined in 44 patients with gastric cancer (8 early, 7 advanced without remote metastasis and 29 metastatic), 13 with colorectal adenoma (2 with focal cancer) and 26 with colorectal carcinoma (8 advanced without metastasis and 18 metastatic) before treatment. An extremely high plasma concentration of VEGF was seen in some cancer patients with metastasis. To discriminate these patients, a cut-off level was determined, considering both the distribution of the sample concentration and the upper limit of 95% confidence area of VEGF in the cancer patients without metastasis. The cut-off value was 108 pg/ml and most cancer patients without metastases had VEGF levels below the cut-off value. In 11 of 29 metastatic gastric cancer patients (38%) and 9 of 18 metastatic colorectal cancer patients (50%), plasma VEGF levels were higher than the cut-off value. Survival was also analysed in the patients with metastasis. It was significantly longer in the patients with low VEGF levels (below the cut-off) than in those with high VEGF levels (logrank test, P = 0.042). 34 patients with metastasis (19 gastric cancer and 15 colorectal cancer) were treated with systemic chemotherapy, and their pretreatment levels of plasma VEGF and conventional tumour markers (CEA and CA19-9) were evaluated in relation to response. The response to chemotherapy was significantly higher in patients with low VEGF levels (< or = 108 pg/ml) than in those with high VEGF levels (P = 0.047). Such a difference was not observed with CEA/CA19-9. In conclusion, plasma VEGF is a useful marker for tumour metastasis and patient survival, and a possible predictive factor for the response of patients with gastrointestinal cancer to chemotherapy.

Adult↗

The effect of spinal destabilization and instrumentation on lumbar intradiscal pressure: an in vitro biomechanical analysis.

STUDY DESIGN: In vitro biomechanical testing was performed in human cadaveric lumbar spines, using pressure needle transducers to analyze the effects of spinal destabilization and instrumentation on lumbar intradiscal pressures. OBJECTIVES: To quantify changes in lumbar intradiscal pressures at three adjacent disc levels under conditions of spinal reconstruction, and to evaluate the possibility of pressure-induced disc pathology secondary to spinal instrumentation. SUMMARY OF BACKGROUND DATA: Lumbar intradiscal pressures under in vivo and in vitro conditions and the use and development of spinal instrumentation have been investigated comprehensively. However, the effects of spinal destabilization and instrumentation on lumbar intradiscal pressure have not been delineated clearly. METHODS: In 11 human cadaveric lumbosacral specimens, specially designed pressure needle transducers quantified intradiscal pressure changes at three adjacent disc levels (L2-L3, proximal; L3-L4, operative; and L4-L5, distal) under four conditions of spinal stability: intact, destabilized, laminar hook and pedicle screw reconstructions. Biomechanical testing was performed under axial compression (0-600 N), anterior flexion (+12.5 degrees) and extension (-12.5 degrees), after which the level of degeneration and disc area (cm2) were quantified. RESULTS: In response to destabilization and instrumentation, proximal disc pressures increased as much as 45%, and operative pressure levels decreased 41-55% (P < 0.05), depending on the instrumentation technique. Linear regression and correlation analyses comparing intradiscal pressure to the grade of disc degeneration were not significant (r = 0.24). CONCLUSIONS: Changes in segmental intradiscal pressure levels occur in response to spinal destabilization and instrumentation (P < 0.05). Intradiscal cyclic pressure differentials drive the metabolic production and exchange of disc substances. Conditions of high or low disc pressure secondary to spinal instrumentation may serve as the impetus for altered metabolic exchange and predispose operative and adjacent levels to disc pathology.

Adult↗

The role of spinal instrumentation in augmenting lumbar posterolateral fusion.

STUDY DESIGN: Using a sheep model, clinically practical posterolateral intertransverse process fusion was successfully achieved and biomechanically tested to determine the load-sharing environment provided by spinal instrumentation and posterolateral fusion mass following solid arthrodesis. OBJECTIVES: To quantify the in vivo load-sharing capacity of spinal instrumentation on augmenting the posterolateral intertransverse fusion. The hypothesis was that transpedicular screw fixation maintains the biomechanical contribution to the posterolateral fusion stability even after successful arthrodesis because of its providing anterior and middle column support. SUMMARY OF BACKGROUND DATA: Although many previous studies have documented the biological and biomechanical advantages of posterolateral fusion, it is known that posterolateral fusion without spinal instrumentation allowed significant remaining motion at the fused segment even after the solid arthrodesis. Whether spinal instrumentation, especially transpedicular screw fixation, augments in vivo posterolateral fusion stability after solid arthrodesis has not been previously investigated. METHODS: Radiographic, macroscopic, and biomechanical analyses of a posterolateral intertransverse process fusion model were performed on 18 sheep at 4 months postoperatively. The load-sharing contribution of the spinal instrumentation was calculated based on the stability with or without spinal instrumentation tested in five loading modalities. Histomorphometry of the vertebral body spanned by spinal instrumentation provided the information regarding the biological effect of the load-sharing capacity of spinal instrumentation on bone remodeling. RESULTS: All sheep who received posterolateral intertransverse process fusion demonstrated successful solid arthrodesis and high biomechanical quality of the posterolateral fusion mass when compared to previous posterolateral fusion models. The significant difference in stiffness between fixation and subsequent fixation removal was observed in flexion, despite maintaining high lateral bending stiffness equivalent to the fixation (with instrumentation) level. This significant load-sharing contribution of spinal instrumentation detected in flexion corresponded to 27% when compared to the fixation level. The qualitative and quantitative bone histology showed 64% of the volumetric density of bone in the fixation group when compared to that of the sham group as well as narrow trabeculae and reduced connection of trabeculae. CONCLUSIONS: The continuance in support offered by transpedicular screw fixation was assured in vivo after the solid posterolateral intertransverse process fusion. This was clearly demonstrated under eccentric loads in a sagittal plane, suggesting that transpedicular screw fixation was able to provide anterior and middle column support and resist eccentric loads.

Analysis of Variance↗

Prosaposin facilitates sciatic nerve regeneration in vivo.

Prosaposin, a multifunctional protein, is the precursor of saposins, which activate sphingolipid hydrolases. In addition to acting as a precursor for saposins, prosaposin has been shown to rescue hippocampal CA1 neurons from lethal ischemic damage in vivo and to promote neurite extension of neuroblastoma cells in vitro. Here we show that prosaposin, when added to a collagen-filled nerve guide after sciatic nerve transection in guinea pigs, increased dramatically the number of regenerating nerve fibers within the guide. To identify the target neurons of prosaposin during peripheral nerve regeneration, we determined the degree of atrophy and chromatolysis of neurons in the spinal anterior horn and dorsal root ganglia on the prosaposin-treated and untreated side. The effect of prosaposin on large spinal neurons and small neurons of the dorsal root ganglion was more conspicuous. Subsequent immunohistochemistry demonstrated that the atrophy of cholinergic large neurons in the anterior horn is prevented to significant extent by prosaposin treatment. These findings suggest that prosaposin promotes peripheral nerve regeneration by acting on alpha-motor neurons in the anterior horn and on small sensory neurons in the dorsal root ganglion. The present study raises the possibility of using prosaposin as a tool for the treatment of peripheral nerve injuries.

Animals↗

A hydrophilic peptide comprising 18 amino acid residues of the prosaposin sequence has neurotrophic activity in vitro and in vivo.

Prosaposin, a 517-amino-acid glycoprotein, not only acts as the precursor of saposin A, B, C, and D but also possesses neurotrophic activity to rescue hippocampal CA1 neurons from ischemic damage in vivo and to promote neurite extension of neuroblastoma cells in vitro. Recently, the trophic activity of prosaposin on human neuroblastoma cells has been shown to reside in the NH2-terminal hydrophilic sequence (LIDNNRTEEILY) of the human saposin C. Here we show that prosaposin, saposin C, and a peptide comprising the 18-amino-acid sequence (18-mer peptide; LSELIINNATEELLIKGL) located in the NH2-terminal hydrophilic sequence of the rat saposin C-domain promoted survival and neurite outgrowth of cultured rat hippocampal neurons in a dose-dependent manner. Moreover, infusion for 7 days of the 18-mer peptide into the lateral ventricle of gerbils, starting either 2 h before or immediately after 3 min of forebrain ischemia, protected ischemia-induced learning disability and hippocampal CA1 neuronal loss. Thus, we ascribe the in vitro and in vivo trophic actions of prosaposin on hippocampal neurons to the linear 18-mer sequence and raise the possibility that this peptide can be used as an agent for the treatment of forebrain ischemic damage.

Amino Acid Sequence↗

The Mitek Mini G2 suture anchor: biomechanical analysis of use in the hand.

We inserted 36 Mitek Mini G2 suture anchors (Mitek Surgical Products, Westwood, MA) into various sites of 14 fresh cadaver hands. A single-strand 0-Ethibond suture (Ethicon, Sommerville, NJ) was threaded through each anchor, inserted into bone, and loaded to failure. In all cases, either the anchor pulled out (11 of 36) or the suture broke (25 of 36). No anchors fractured. We also measured the breaking strength of six types of suture material (without anchors) commonly used by hand surgeons; all failed at much lower loads than those generated in our anchor pullout model. We conclude that the Mitek Mini G2 suture anchor possesses sufficient pullout strength for tendon and ligament fixation in the hand, including the distal phalanx.

Adult↗

Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA).

An unstable expansion of CAG repeat in the coding region of the DRPLA gene on chromosome 12p is the mutation specific for hereditary dentatorubral-pallidoluysian atrophy (DRPLA). We studied the CAG expansion in brain and other tissues from six unrelated DRPLA patients. The CAG repeat lengths showed distinct differences between tissues. The sizes of the CAG expansion in various regions of the brain except the cerebellum were generally larger by several repeats than in other peripheral tissues. Brain samples showed greater variation of the expansion compared with other tissues, but neither the size of the CAG expansion nor the degree of CAG repeat variation parallels the detailed findings of neuropathological involvement. We conclude that somatic instabilities of the CAG repeat cause tissue variability of the CAG repeat size in DRPLA but other region or cell type-specific factors would be involved to explain the selectivity of cell damage in DRPLA.

Adult↗

The 3'-untranslated region of mouse myelin basic protein gene increases the amount of mRNA in immortalized mouse oligodendrocytes.

The 3'-untranslated region (UTR) of the myelin basic protein (MBP) mRNA has been found previously to enhance the translational efficiency of the coding region by two-fold in cell-free translational systems. In this study, we transfected eukaryotic expression vectors containing the reporter cDNA for chloramphenicol acetyltransferase (CAT) with or without the mouse MBP cDNA 3'-UTR into cultured cells. CAT activity in the mouse oligodendrocyte cell line, N20.1, transfected with a CAT cDNA containing the MBP 3'-UTR [CAT-MBP 3'-UTR], was twice as high as that of the CAT cDNA without the 3'-UTR; CAT activities for the two constructs were the same in the mouse fibroblast cell line, NIH 3T3. Using reverse transcriptase PCR quantitative analysis, the expression of mRNA was determined. The level of the [CAT-MBP 3'-UTR] mRNA was about ten times higher than CAT mRNA in N20.1 cells but they were the same in NIH 3T3 cells. We conclude that the 3'-UTR of MBP gene increases gene expression at both the mRNA and protein levels in oligodrocyte cell lines, probably through a post-transcriptional mechanism such a message stabilization.

3T3 Cells↗

Biomechanical analysis of cervical stabilization systems. An assessment of transpedicular screw fixation in the cervical spine.

STUDY DESIGN: The biomechanical stability of seven cervical reconstruction methods including the transpedicular screw fixation was evaluated under four instability patterns. These four modalities, based on the range and grade of instability, allowed a reproducible biomechanical assessment to establish the in vitro role of internal fixation in the cervical spine. OBJECTIVES: This study biomechanically investigated the stability of seven reconstruction methods in the cervical spine as influenced by four instability patterns and assessed whether three-column fixation for the cervical spine using transpedicular screw fixation would provide increased stability over that of conventional cervical fixation systems. METHODS: A total of 24 calf cervical spine specimens were divided into four experimental groups. The spinal constructs including seven reconstruction techniques--the posterior AO titanium reconstruction plate, Bohlman's posterior triple-wiring, transpedicular screw fixation, anterior iliac bone graft, anterior AcroMed plate, anterior AO titanium locking plate, and combined fixation with the AO anterior plate and posterior triple-wiring--were tested under four loading modes. RESULTS: Anterior plating methods provided less stability than that of posterior constructs under axial, torsional, and flexural loading conditions. Exclusive posterior procedures provided increased stability compared with the intact spine in one level fixation, however, did not sustain the torsional stability when the anterior and middle column was eliminated in two-level fixation. The stabilizing capabilities of both the combined fixation and transpedicular screw fixation were clearly demonstrated in all loading modes, however, those of the latter were superior in multilevel fixation. CONCLUSION: Front and back approaches, employing the anterior plate and posterior triple-wiring, and transpedicular screw fixation demonstrated clear biomechanical advantages when the extent of instability increased to three-column or multilevel. Three-column fixation for the cervical spine using transpedicular screw fixation offers increased stability over that of conventional cervical fixation systems, particularly in multiple level constructs.

Animals↗

Protection by prosaposin against ischemia-induced learning disability and neuronal loss.

Prosaposin, the protein precursor of saposins A, B, C, and D which activate sphingolipid hydrolases, is abundant in several brain regions including the hippocampus. We infused prosaposin continuously for 7 days into the lateral ventricle of gerbils starting 3 hours before 3-min of forebrain ischemia. Using the step-down passive avoidance task, we demonstrated that ischemia-induced learning disability is prevented almost completely by prosaposin infusion. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 field of the hippocampus as well as synapses within the strata moleculare, lacunosum/radiatum and oriens of the field were significantly more numerous in gerbils infused with prosaposin infusion than in those receiving saline infusion. These findings suggest that prosaposin possesses neurotrotrophic activity to protect hippocampal CA1 neurons from lethal ischemic damage.

Animals↗