Systemic delivery of (1R-1-benzo thiophen-5-yl-2[2-diethylamino)-ethoxy] ethanol hydrochloride (T-588) prevented long-term depression (LTD) of the parallel fiber (PF)-Purkinje cell (PC) synapse induced by conjunctive climbing fiber and PF stimulation in vivo.However, similar concentrations of T-588 in the brains of behaving mice and rats affected neither motor learning in the rotorod test nor the learning of motor timing during classical conditioning of the eyeblink reflex. Rats given doses of T-588 that prevented PF-PC LTD were as proficient as controls in learning to adapt the timing of their conditioned eyeblink response to a 150-or 350-ms change in the timing of the paradigm. The experiment indicates that PF-PC LTD under control of the climbing fibers is not required for general motor adaptation or the learning of response timing in two common models of motor learning for which the cerebellum has been implicated. Alternative mechanisms for motor timing and possible functions for LTD in protection from excitotoxicity are discussed.cerebellum ͉ eyeblink ͉ field potentials ͉ rotorod A longstanding hypothesis concerning cerebellar function has been the proposal that it serves as the repository for new motor skills through plasticity of the parallel fiber (PF)-Purkinje cell (PC) synapse (1, 2). In the prevailing hypothesis of ''cerebellar learning,'' the acquisition of new skills is controlled by climbing fibers (CFs), which function to depress the strength of the PF-PC synapse when the two afferents are conjointly active. The cerebellar learning hypothesis has inspired much research since the demonstration, in vivo, that near-synchronous activation of CFs and PFs by direct electrical stimulation depressed the strength of the excitatory potentials triggered by PFs in PCs (3). Because the depression required repeated pairings of CF and PF synaptic input and was retained for many hours, the phenomenon has been termed cerebellar long-term depression (LTD) and has been invoked to explain the acquisition and lifetime retention of many motor skills, including learned motor timing, reflex adaptation, and procedural and implicit learning (4).A substantial body of evidence has established the necessary intracellular events that produce PC LTD in vitro, and these events have been assumed to relate to motor learning in vivo. Moreover, a recent experiment showed that mouse PCs genetically modified to lack protein kinase C (PKC) function could not undergo LTD (5, 6); when such transgenic mice were tested in classical eyeblink conditioning, they were unable to learn the appropriate motor timing of conditioned eyeblinks [conditioned response (CR)] (7). That finding, complemented by the finding that cerebellar decortication also impaired the learned motor timing of CRs (8), has sustained the hypothesis that PF-PC LTD is required for motor learning. However, it is also evident that, up to this time, it has not been determined whether LTD occurs in awake animals as they acquire and retain new motor skills. Thus, it has been diffic...

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Abstract:Introduction: Few studies have investigated the influence of cage subsidence patterns (intraoperative endplate injury or late-onset cage settling) on bony fusion and clinical outcomes in lateral interbody fusion (LIF). This retrospective study was performed to compare the fusion rate and clinical outcomes of cage subsidence patterns in LIF at one year after surgery.Methods: Participants included 93 patients (aged 69.0±0.8 years; 184 segments) who underwent LIF with bilateral pedicle screw fixation. All segments were evaluated by computed tomography and classified into three groups: Segment E (intraoperative endplate injury, identified immediately postoperatively); Segment S (late-onset settling, identified at 3 months or later); or Segment N (no subsidence). We compared patient characteristics, surgical parameters and fusion status at 1 year for the three subsidence groups. Patients were classified into four groups: Group E (at least one Segment E), Group S (at least one Segment S), Group ES (both Segments E and S), or Group N (Segment N alone). Visual analog scales (VASs) and the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were compared for the four patient groups.Results: 184 segments were classified: 31 as Segment E (16.8%), 21 as Segment S (11.4%), and 132 as Segment N (71.7%). Segment E demonstrated significantly lower bone mineral density (-1.7 SD of T-score, p=0.003). Segment S demonstrated a significantly higher rate of polyetheretherketone (PEEK) cages (100%, p=0.03) and a significantly lower fusion rate (23.8%, p=0.01). There were no significant differences in VAS or in any of the JOABPEQ domains among the four patient groups.Conclusions: Intraoperative endplate injury was significantly related to bone quality, and late-onset settling was related to PEEK cages. Late-onset settling demonstrated a worse fusion rate. However, there were no significant differences in clinical outcomes among the subsidence patterns.

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Progressive neuronal loss in Alzheimer's disease (AD) is considered to be a consequence of the neurotoxic properties of amyloid-␤ peptides (A␤). T-817MA (1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate) was screened as a candidate therapeutic agent for the treatment of AD based on its neuroprotective potency against A␤-induced neurotoxicity and its effect of enhancing axonal regeneration in the sciatic nerve axotomy model. The neuroprotective effect of T-817MA against A␤(1-42) or oxidative stress-induced neurotoxicity was assessed using a coculture of rat cortical neurons with glia.

Study DesignRetrospective study.PurposeTo compare intraoperative endplate injury cases and no injury cases in consecutive series and to identify predisposing factors for intraoperative endplate injury.Overview of LiteratureUnintended endplate violation and subsequent cage subsidence is an intraoperative complication of extreme lateral interbody fusion (XLIF). It is still unknown whether it is derived from inexperienced surgical technique or patients' inherent problems.MethodsConsecutive patients (n=102; mean age, 69.0±0.8 years) underwent XLIF at 201 levels at a single institute. Preoperative and immediately postoperative radiographs were compared and cases with intraoperative endplate injury were identified. Various parameters were reviewed in each patient and compared between the injury and no injury groups.ResultsTwenty one levels (10.4%) had signs of intraoperative endplate injury. The injury group had a significantly higher rate of females (p=0.002), lower bone mineral density (BMD) (p=0.02), higher rate of polyetheretherketone as cage material (p=0.04), and taller cage height (p=0.03) compared with the no injury group. Multivariate analysis indicated that a T-score of BMD as a negative (odds ratio, 0.52; 95% confidence interval, 0.27–0.93; p=0.03) and cage height as a positive (odds ratio, 1.84; 95% confidence interval, 1.01–3.17; p=0.03) were predisposing factors for intraoperative endplate injury.ConclusionsIntraoperative endplate injury is correlated significantly with reduced BMD and taller cage height. Precise evaluation of bone quality and treatment for osteoporosis might be important and care should be taken not to choose excessively taller cage.

Purpose Diabetes mellitus (DM) is known as an important risk factor for surgical site infection (SSI) in spine surgery. It is still unclear however which DM-related parameters have stronger influence on SSI. The purpose of this study is to determine predisposing factors for SSI following spinal instrumentation surgery for patients with DM. Methods 110 DM patients (66 males and 44 females) who underwent spinal instrumentation surgery in one institute were enrolled in this study. For each patient, various preoperative or intraoperative parameters were reviewed from medical records. Patients were divided into two groups (SSI or non-SSI) based on the postoperative course. Each parameter between these two groups was compared. Univariate and multivariate analyses were performed to determine predisposing factor for SSI. Results The SSI group consisted of 11 patients (10 %), and the non-SSI group of 99 patients (90 %). Univariate analysis revealed that preoperative proteinuria (p = 0.01), operation time (p = 0.04) and estimated blood loss (p = 0.02) were significantly higher in the SSI group compared to the non-SSI group. Multivariate logistic regression identified preoperative proteinuria as a statistically significant predictor of SSI (OR 6.28, 95 % CI 1.58-25.0, p = 0.009).Conclusions Proteinuria is a significant predisposing factor for SSI in spinal instrumentation surgery for DM patients. DM patients with proteinuria who are likely to suffer latent nephropathy have a potential risk for SSI. For them less invasive surgery is recommended for spinal instrumentation. In this retrospective study, there was no significant difference of preoperative condition in glycemic control between the two groups.