Spine Types Research Articles

Radiographic Categorization of the Hip-spine Syndrome in the Setting of Hip Osteoarthritis and Sagittal Spinal Malalignment

Interplay between degenerative hip and spine conditions (Hip-Spine Syndrome [HiSS]) warrants effective communication between respective surgeons. We identified radiographic parameters to distinguish a subset of patients with HiSS by evaluating hip osteoarthritis (HOA) in patients with and without spinopelvic malalignment, categorizing patients into respective HiSS types, and comparing radiographic parameters. All patients with full-body orthogonal radiography from 2013 to 2016 were reviewed (n = 1,389). Using sagittal/coronal hip radiographs, HOA (Kellgren-Lawrence Grade) was noted, and pelvic incidence-lumbar lordosis mismatch (PI-LL) > 10° was considered spinal malalignment. Patients groups included non-HiSS (PI-LL ≤ 10°/Grade 0/n = 444), Hip (PI-LL ≤ 10°/Grade 3-4/n = 78), Spine (PI-LL > 10°/Grade 0/n = 297), or Hip-Spine (PI-LL > 10°/Grade 3-4/n = 30). Parameters were compared using ANOVA with post-hoc Bonferroni analysis. HiSS Hip type patients had less hip extension capability compared with non-HiSS, Spine, and Hip-Spine type patients, reflected by lowest pelvic tilt (PT)/sagittal retroversion (11.3° versus 16.5°/29.2°/25.2°, respectively) and less hip extension per sacrofemoral angle (10.1° versus 19.5°/28.4°/23.1°, respectively) (P < 0.001), as well as 4.7° increase in anterior tilt/sagittal anteversion compared with age-matched individuals. Hip-Spine type patients had less pelvic retroversion than Spine type patients (P = 0.045); these differences were greater when referenced to age-matched individuals (P < 0.001). Hip-Spine type patients had less hip extension than Spine type patients (P = 0.013). Hip type patients had greater knee flexion than non-HiSS type patients (6.4° versus 2.6°; P < 0.001). Moreover, Hip-Spine type patients had comparable lower extremity alignment compared with Spine type patients, except for greater posterior pelvic shift. Our novel HiSS categorization used established classification methods and supported PT use to potentially improve the ability to discern HiSS types/pathologies in a subset of patients with HOA and spinal sagittal malalignment. HOA grade 3 to 4 with PT <15° are categorized as Hip type and those with PT >25° are Hip-Spine type with sagittal malalignment, which may impact acetabular arthroplasty component placement.

Determination of S1 screw adjustment parameters using by 3D CT images in healthy subjects

Background: The aim of this study was to investigate the anthropometry of the posterior superior iliac spine (PSIS) types in the Turkish population and to determine the safe limits of the length and angle of the sacrum by the posterior lumber approach in lumbosacral instrumentation surgery. Material and Method: Sacral regions (left and right pedicle lengths and pedicle angles) and PSIS types of healthy subjects were evaluated using 3D images. Results: A total of 111 patients (58 males and 53 females) were included in the study. The mean age was 46.9 ± 14.8 in males and 44.3 ± 16.4 in females. In men, the right pedicle length was 52.83 mm, the left pedicle length was 53.81 mm, the right pedicle angle was 35.84, the left pedicle angle was 35.13, and the caudal angle was 39.24 degrees. In females, right pedicle length was 48.88 mm, left pedicle length was 49.28 mm, right and left pedicle angle was 35.83, and caudal angle was 39.24 degrees. PSIS type 1 was found to be 58.6%, type 2 32.4% and type 3 9%. Conclusion: Optimal screw lengths, angles and proper screw orientations can be easily and safely operated in posterior stabilization. In this study, morphometric and anthropometric information related to sacral screw orientation were also determined. These data may help to prevent surgical complications by contributing to the surgeon about preoperative anatomical structure in lumbosacral surgery stabilization procedures.

224. Does Roussouly type affect revision surgery rates for proximal junctional kyphosis (PJK) and adjacent segment degeneration (ASD) after fusion for adult scoliosis?

BACKGROUND CONTEXT As spine types have been classified into 4 Roussouly types based upon their sacral slope and shape, it is unclear if certain types lead to higher or lower rates of adjacent segment breakdown after spinal fusion for scoliosis. PURPOSE There are certain Roussouly types that may predispose patients to a higher rate of proximal segment breakdown compared to others. STUDY DESIGN/SETTING Retrospective review of a single center North American spine center scoliosis cases from 2004 to 2016. PATIENT SAMPLE A total of 193 patients with minimum 2-year follow up were included. Mean follow up was 45 months. OUTCOME MEASURES PJK and ASD can occur after fusion for adult scoliosis. It is unclear if one Roussouly type predisposes or protects against proximal segment breakdown. We wished to investigate if certain Roussouly types were associated with higher or lower rates of adjacent segment breakdown. METHODS Retrospective review at a single North American spine center scoliosis cases. Radiographs were reviewed, and all cases were classified by Roussouly type (1 to 4) based upon preoperative 3-foot standing lateral radiographs. Records were reviewed for revision surgery proximal to the construct only, for either ASD or PJK, and patients were excluded if surgery was performed for infection, wound problems, implant failure, or surgery at the original index levels. Fusion types were classified as short ( RESULTS Patients were classified as type 1: 48, type 2: 66, type 3: 56, and type 4: 23. When evaluated by Roussouly type, there was no difference in revision surgery rates for ASD or PJK. However, when evaluating only type 2 spines, short fusion had a revision surgery rate of 35.1% (13/37) compared to 13.8% (7/29) for long fusions (p=0.0491). With regards to the entire cohort of 193 patients, short segment fusions had a revision surgery rate at the proximal level of 33.6% (36/107) compared to a long fusion rate of 16.3% (14/86), p=0.0014. CONCLUSIONS Short segment fusions had a statistically higher rate of surgery for proximal pathology for all spine types, and Roussouly type 2 spines had a higher rate of proximal pathology surgery with short fusions compared to long fusions. We could not detect a difference of revision surgery rates for proximal pathology for adult scoliosis based solely upon Roussouly type. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Increases in dendritic spine density in BLA without metabolic changes in a rodent model of PTSD.

Imaging studies have shown abnormal amygdala function in patients with posttraumatic stress disorder (PTSD). In addition, alterations in synaptic plasticity have been associated with psychiatric disorders and previous reports have indicated alterations in the amygdala morphology, especially in basolateral (BLA) neurons, are associated with stress-related disorders. Since, some individuals exposed to a traumatic event develop PTSD, the goals of this study were to evaluate the early effects of PTSD on amygdala glucose metabolism and analyze the possible BLA dendritic spine plasticity in animals with different levels of behavioral response. We employed the inescapable footshock protocol as an experimental model of PTSD and the animals were classified according to the duration of their freezing behavior into distinct groups: "extreme behavioral response" (EBR) and "minimal behavioral response". We evaluated the amygdala glucose metabolism at baseline (before the stress protocol) and immediately after the situational reminder using the microPET and the radiopharmaceutical 18F-FDG. The BLA dendritic spines were analyzed according to their number, density, shape and morphometric parameters. Our results show the EBR animals exhibited longer freezing behavior and increased proximal dendritic spines density in the BLA neurons. Neither the amygdaloid glucose metabolism, the types of dendritic spines nor their morphometric parameters showed statistically significant differences. The extreme behavior response induced by this PTSD protocol produces an early increase in BLA spine density, which is unassociated with either additional changes in the shape of spines or metabolic changes in the whole amygdala of Wistar rats.

Motor learning induces plastic changes in Purkinje cell dendritic spines in the rat cerebellum

IntroductionThe paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. MethodsAdult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. ResultsThe learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. ConclusionThe initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent “silencing” of memory consolidation processes, based on the regulation of the neuronal excitability.

Nanoscale imaging reveals miRNA-mediated control of functional states of dendritic spines

Dendritic spines are major loci of excitatory inputs and undergo activity-dependent structural changes that contribute to synaptic plasticity and memory formation. Despite the existence of various classification types of spines, how they arise and which molecular components trigger their structural plasticity remain elusive. microRNAs (miRNAs) have emerged as critical regulators of synapse development and plasticity via their control of gene expression. Brain-specific miR-134s likely regulate the morphological maturation of spines, but their subcellular distributions and functional impacts have rarely been assessed. Here, we exploited atomic force microscopy to visualize in situ miR-134s, which indicated that they are mainly distributed at nearby dendritic shafts and necks of spines. The abundance of miR-134s varied between morphologically and functionally distinct spine types, and their amounts were inversely correlated with their postulated maturation stages. Moreover, spines exhibited reduced contents of miR-134s when selectively stimulated with beads containing brain-derived neurotropic factor (BDNF). Taken together, in situ visualizations of miRNAs provided unprecedented insights into the "inverse synaptic-tagging" roles of miR-134s that are selective to inactive/irrelevant synapses and potentially a molecular means for modifying synaptic connectivity via structural alteration.

Antagonizing Increased miR-135a Levels at the Chronic Stage of Experimental TLE Reduces Spontaneous Recurrent Seizures.

Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The antiepileptic drugs currently available to treat mTLE are ineffective in one-third of patients and lack disease-modifying effects. miRNAs, a class of small noncoding RNAs which control gene expression at the post-transcriptional level, play a key role in the pathogenesis of mTLE and other epilepsies. Although manipulation of miRNAs at acute stages has been reported to reduce subsequent spontaneous seizures, it is uncertain whether targeting miRNAs at chronic stages of mTLE can also reduce seizures. Furthermore, the functional role and downstream targets of most epilepsy-associated miRNAs remain poorly understood. Here, we show that miR-135a is selectively upregulated within neurons in epileptic brain and report that targeting miR-135a in vivo using antagomirs after onset of spontaneous recurrent seizures can reduce seizure activity at the chronic stage of experimental mTLE in male mice. Further, by using an unbiased approach combining immunoprecipitation and RNA sequencing, we identify several novel neuronal targets of miR-135a, including Mef2a Mef2 proteins are key regulators of excitatory synapse density. Mef2a and miR-135a show reciprocal expression regulation in human (of both sexes) and experimental TLE, and miR-135a regulates dendritic spine number and type through Mef2. Together, our data show that miR-135a is target for reducing seizure activity in chronic epilepsy, and that deregulation of miR-135a in epilepsy may alter Mef2a expression and thereby affect synaptic function and plasticity.SIGNIFICANCE STATEMENT miRNAs are post-transcriptional regulators of gene expression with roles in the pathogenesis of epilepsy. However, the precise mechanism of action and therapeutic potential of most epilepsy-associated miRNAs remain poorly understood. Our study reveals dramatic upregulation of the key neuronal miRNA miR-135a in both experimental and human mesial temporal lobe epilepsy. Silencing miR-135a in experimental temporal lobe epilepsy reduces seizure activity at the spontaneous recurrent seizure stage. These data support the exciting possibility that miRNAs can be targeted to combat seizures after spontaneous seizure activity has been established. Further, by using unbiased approaches novel neuronal targets of miR-135a, including members of the Mef2 protein family, are identified that begin to explain how deregulation of miR-135a may contribute to epilepsy.

Reconstruction of vertebral body in thoracolumbar AO type A post-traumatic fractures by balloon kyphoplasty: a series of 85 patients with a long follow-up and review of the literature.

Traumatic fractures of the thoracolumbar spine are common injuries, accounting for approximately 90% of all spinal traumas. Optimal management of these fractures still gives rises to much debate in the literature. Currently, one of the treatment options in young patients with stable traumatic vertebral fractures is conservative treatment using braces. Kyphoplasty as a minimally invasive procedure has been shown to be effective in stabilizing vertebral body fractures, resulting in immediate pain relief and improving physical function with early return to work activity. The aim of our study was to report VAS, ODI scores, and kyphosis correction following treatment. This is a retrospective study to investigate the clinical and radiological results 10 years after percutaneous balloon kyphoplasty followed by cement augmentation with polymethylmethacrylate (PMMA) or calcium phosphate cements (CPC), according to age, in 85 consecutive patients affected by 91 AO spine type A traumatic fractures of the thoracolumbar spine (A1, A2, and A3). Clinical follow-up was performed with the Visual Analogic Scale (VAS) at the preoperative visit and in the postoperative follow-up after 1 week, 1, 6, 12 months, and each year up to 10 years. Additionally, the Oswestry Disability Index (ODI) improvement was calculated as the difference between the ODI scores at the preoperative visit and at final follow-up. Finally, the Cobb angle from this cohort was assessed before surgery, immediately postoperatively, and at the end of follow-up. Kyphoplasty markedly improved pain and resulted in statistically significant vertebral height restoration and normalization of morphologic shape indexes that remained stable for at least 10 years following treatment. The present study showed that kyphoplasty and cement augmentation are an effective method of treatment for selected type A fractures.

Influence of between-joists bridging elements on static and dynamic response of wood joisted floors

Excessive vertical vibration of lightweight floors caused by walking or similar activities can be annoying to building occupants. Previous studies have shown that the vibrational performance of floors having wood joists is enhanced by installing one or more lines of bridging elements that form transverse spines in the across-span direction. This paper presents an experimental study that defined relationships between the effective flexural rigidity of such spines and response characteristics of wood joisted floors. Behaviors of spines having both normal and special types of bridging elements were investigated, with the special types of elements able to create a broad range of spine flexural rigidities. It was found that all types of transverse bridging spines have a small influence on fundamental natural frequency but can increase higher order modal frequencies considerably. Relatively stiff types of transverse bridging spines reduced static deflections caused by concentrated gravity forces considerably. An experimental method is presented for quantifying effective flexural rigidities of transverse bridging spines. Suggestions are made concerning application of the research findings in vibration serviceability design of lightweight wood joisted floors.

Moderate Interrater and Substantial Intrarater Reproducibility of the Roussouly Classification System in Patients With Adult Spinal Deformity

Study DesignReproducibility study of a classification system. ObjectivesTo provide the inter- and intrarater reproducibility of the Roussouly Classification System in a single-center prospective cohort of patients referred for Adult Spinal Deformity. Summary of Background DataThe Roussouly Classification System was developed to describe the variation in sagittal spine shape in normal individuals. A recent study suggests that patients' spine types could influence the outcome following spinal surgery. The utility of a classification system depends largely on its reproducibility. MethodsSixty-four consecutive patients were included in a blinded test-retest setting using digital radiographs. All ratings were performed by four spine surgeons with different levels of experience. There was a 14-day interval between the two reading sessions. Inter- and intrarater reproducibility was calculated using Fleiss Kappa and crude agreement percentages. ResultsWe found moderate interrater (κ = 0.60) and substantial intrarater (κ = 0.68) reproducibility. All 4 raters agreed on the Roussouly type in 47% of the cases. The most experienced rater had significantly higher intrarater reliability compared to the least experienced rater (κ = 0.57 vs 0.78). The two most experienced raters also had the highest crude agreement percentage (75%); however, they also had a significant difference in distribution of spine types. ConclusionThe current study presents moderate interrater and substantial intrarater reliability of the Roussouly Classification System. These findings are acceptable and comparable to previous results of reproducibility for a classification system in patients with Adult Spinal Deformity. Additional studies are requested to validate these findings as well as to further investigate the impact of the classification system on outcome following surgery.

α4βδ GABAA Receptors Trigger Synaptic Pruning and Reduce Dendritic Length of Female Mouse CA3 Hippocampal Pyramidal Cells at Puberty

Synaptic pruning during adolescence is critical for optimal cognition. The CA3 hippocampus contains unique spine types and plays a pivotal role in pattern separation and seizure generation, where sex differences exist, but adolescent pruning has only been studied in the male. Thus, for the present study we assessed pruning of specific spine types in the CA3 hippocampus during adolescence and investigated a possible mechanism in the female mouse. To this end, we used Golgi-impregnated brains from pubertal (∼PND 35, assessed by vaginal opening) and post-pubertal (PND 56) mice. Spine density was assessed from z-stack (0.1-μm steps) images taken using a Nikon DS-U3 camera through a Nikon Eclipse Ci-L microscope and analyzed with NIS Elements. Spine density decreased significantly (P < 0.05) during adolescence, with 50–60% decreases in mushroom and stubby spine-types (P < 0.05, ∼PND35 vs. PND56) in non-proestrous mice. This was associated with decreases in kalirin-7, a spine protein which stabilizes the cytoskeleton and is required for spine maintenance. Because our previous findings suggest that pubertal increases in α4βδ GABAA receptors (GABARs) trigger pruning in CA1, we investigated their role in CA3. α4 expression in CA3 hippocampus increased 4-fold at puberty (P < 0.05), assessed by immunostaining and verified electrophysiologically by an increased response to gaboxadol (100 nM), which is selective for α4βδ. Knock-out of α4 prevented the pubertal decrease in kalirin-7 and synaptic pruning and also increased the dendritic length, demonstrating a functional link. These data suggest that pubertal α4βδ GABARs alter dendritic morphology and trigger pruning in female CA3 hippocampus.

Partial Vertebrectomies without Instrumented Stabilization During En Bloc Resection of Primary Bronchogenic Carcinomas Invading the Spine: Feasibility Study and Results on Spine Balance

It is unknown whether spinal instrumentation is required to prevent deformity after partial vertebrectomy in the treatment of primary bronchogenic carcinomas invading the spine (PBCIS). In this study, we focus on the postoperative spine deformity in patients who underwent operation for partial vertebrectomies without instrumentation during en bloc PBCIS resection. Our objective was to determine whether deformity depends on the type of vertebral resection and if any vertebral resection threshold can be observed to justify additional spinal instrumentation. This is a retrospective study, including all patients with PBCIS operated without spinal instrumentation from 2009 to 2018. Partial vertebrectomies were classified into categories A, B, and C depending on vertebral resection. Patients had long-term radiologic follow-up to assess the spine deformity evolution. Eighteen patients were included. The median follow-up was 27 months. Four patients underwent a secondary posterior instrumentation surgical procedure due to progressive spinal deformity. A low-risk group of deformation was characterized as type A resection and type B resection on less than 3 vertebrae. There are no validated criteria to justify a systematic spinal instrumentation when performing a partial vertebrectomy during en bloc resection of PBCIS. Performed alone without spine instrumentation, both type A and type B resections on less than 3 resected vertebrae were not subject to sagittal and coronal deformity even after a long follow-up, emphasizing that a systematic stabilization is not needed in this low-risk group. These results could help to reduce the perioperative morbidity of these procedures that are usually long and complex.

Selective Loss of Thin Spines in Area 7a of the Primate Intraparietal Sulcus Predicts Age-Related Working Memory Impairment.

Brodmann area 7a of the parietal cortex is active during working memory tasks in humans and nonhuman primates, but the composition and density of dendritic spines in area 7a and their relevance both to working memory and cognitive aging remain unexplored. Aged monkeys have impaired working memory, and we have previously shown that this age-induced cognitive impairment is partially mediated by a loss of thin spines in prefrontal cortex area 46, a critical area for working memory. Because area 46 is reciprocally connected with area 7a of the parietal cortex and 7a mediates visual attention integration, we hypothesized that thin spine density in area 7a would correlate with working memory performance as well. To investigate the synaptic profile of area 7a and its relevance to working memory and cognitive aging, we investigated differences in spine type and density in layer III pyramidal cells of area 7a in young and aged, male and female rhesus macaques (Macaca mulatta) that were cognitively assessed using the delayed response test of working memory. Area 7a shows age-related loss of thin spines, and thin spine density positively correlates with delayed response performance in aged monkeys. In contrast, these cells show no age-related changes in dendritic length or branching. These changes mirror age-related changes in area 46 but are distinct from other neocortical regions, such as V1. These findings support our hypothesis that cognitive aging is driven primarily by synaptic changes, and more specifically by changes in thin spines, in key association areas.SIGNIFICANCE STATEMENT This study advances our understanding of cognitive aging by demonstrating the relevance of area 7a thin spines to working memory performance. This study is the first to look at cognitive aging in the intraparietal sulcus, and also the first to report spine or dendritic measures for area 7a in either young adult or aged nonhuman primates. These results contribute to the hypothesis that thin spines support working memory performance and confirm our prior observation that cognitive aging is driven by synaptic changes rather than changes in dendritic morphology or neuron death. Importantly, these data show that age-related working memory changes are not limited to disruptions of the prefrontal cortex but also include an association region heavily interconnected with prefrontal cortex.

Chronic asthma-induced behavioral and hippocampal neuronal morphological changes are concurrent with BDNF, cofilin1 and Cdc42/RhoA alterations in immature mice

IntroductionRecent studies have found that persistent hypoxia caused by chronic asthma, especially during childhood, affects the development and function of the brain, but the mechanism is unclear. In the present study, BDNF and its signal pathway was investigated in mediating chronic asthma induced-neuronal changes that lead to behavior alterations. MethodsThe chronic asthma model was induced by sensitization with ovalbumin for more than 9 weeks in immature mice. Morris water maze test (MWMT), open field test (OFT) and elevated plus maze test (EPMT) were used to conduct behavioral evaluation. Neuronal morphology in hippocampal CA1, CA3 and DG was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. BDNF signaling pathway related molecules was determined by Western blotting. ResultsChronic asthma does affect the behavioral performances of immature mice evaluated in MWMT, OFT, and EPMT. The analysis by three-dimensional reconstruction software found that following the behavioral alteration of asthmatic mice, dendritic changes also occurred in hippocampal neurons, including shortened dendrite length, significantly reduced number of dendritic branches, decreased density of dendritic spines, and reduced percentage of functional dendritic spine types. At the same time, by immunofluorescence and western blotting, we also found that alterations in dendritic morphology were consistent with activation of cofilin1 and changes in BDNF-Cdc42/RhoA levels. Some of the changes mentioned above can be alleviated by intranasal administration of budesonide. ConclusionOur data suggest that response similar to nicotine withdrawal or/and hypoxia induced by childhood chronic asthma enhances the BDNF-Cdc42/RhoA signaling pathway and activates cofilin1, leading to the remodeling of actin, causing the loss of dendritic spines and atrophy of dendrites, eventually resulting in behavioral alterations.

Anterior inferior iliac spine morphology: quantitative and qualitative assessment in an asymptomatic population.

To assess the prevalence of anterior inferior iliac spine (AIIS) types, and to investigate the quantitative measurements that characterize AIIS morphology in an asymptomatic adult population. In this prospective study, 358 hips from 179 consecutive subjects (age range, 19-82 years; 91 males, 88 females), who underwent CT examination for reasons other than hip problems and were negative for hip impingement test, were analyzed. AIIS types were determined (1, flat wall of the ilium between distal end of AIIS and acetebular rim; 2, bony eminence between distal end of AIIS and acetebular rim; and 3, extension of AIIS to the anterior superior acetebular rim) and AIIS tip angle (TA), direct distance (DD) of the anterior acetabular rim to AIIS as well as projectional distances in vertical (VD) and horizontal (HD) planes were measured. Age- and gender-related factors were searched using two-way ANOVA test under three age groups (18-39, 40-59, and ≥ 60years). There were 238 (66.5%) type 1, 118 (33.0%) type 2, and two (0.5%) type 3 AIISs, with significant difference between AIIS types among age groups and genders (P < 0.001). VD and DD showed age- and gender-related (P < 0.001, P < 0.001), and TA demonstrated gender-related differences (P < 0.001). Inter-observer agreement was good for TA and moderate to poor for other measurements. Type 1 AIIS is the most common shape across all age groups in adult females and in young and middle-aged adult males. TA, DD, and VD might be reliably used for the evaluation of AIIS morphology.

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal

Heightened distractibility is a core symptom of Attention Deficit Hyperactivity Disorder (ADHD). Effective treatment is normally with chronic orally administered psychostimulants including amphetamine. Treatment prevents worsening of symptoms but the site of therapeutic processes, and their nature, is unknown. Mounting evidence suggests that the superior colliculus (SC) is a key substrate in distractibility and a therapeutic target, so we assessed whether therapeutically-relevant changes are induced in this structure by chronic oral amphetamine. We hypothesized that amphetamine would alter visual responses and morphological measures. Six-week old healthy male rats were treated with oral amphetamine (2, 5 or 10 mg/kg) or a vehicle for one month after which local field potential and multiunit recordings were made from the superficial layers of the SC in response to whole-field light flashes in withdrawal. Rapid Golgi staining was also used to assess dendritic spines, and synaptophysin staining was used to assess synaptic integrity. Chronic amphetamine increased local field potential responses at higher doses, and increased synaptophysin expression, suggesting enhanced visual input involving presynaptic remodelling. No comparable increases in multiunit activity were found suggesting amphetamine suppresses collicular output activity, counterbalancing the increased input. We also report, for the first time, five different dendritic spine types in the superficial layers and show these to be unaffected by amphetamine, indicating that suppression does not involve gross postsynaptic structural alterations. In conclusion, we suggest that amphetamine produces changes at the collicular level that potentially stabilise the structure and may prevent the worsening of symptoms in disorders like ADHD.

Novel antidepressant effects of Paeonol alleviate neuronal injury with concomitant alterations in BDNF, Rac1 and RhoA levels in chronic unpredictable mild stress rats.

Increasing evidence has suggested that major depressive disorder (MDD) is highly associated with brain-derived neurotrophic factor (BDNF) levels, dendrites atrophy, and loss of dendritic spines, especially in emotion-associated brain regions including the hippocampus. Paeonol is a kind of polyphenols natural product with a variety of therapeutic effects. Recent studies have reported its antidepressant effects. However, it is unclear what signaling pathways contribute to improve MDD. The present study investigated the effect of Paeonol on hippocampal neuronal morphology and its possible signaling pathways in chronic unpredictable mild stress (CUMS) rat model. Using CUMS rat model, the antidepressant-like effect of Paeonol was validated via depression-related behavioral tests. Neuronal morphology in hippocampal CA1 and DG was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. BDNF signaling pathway-related molecules was determined by Western blotting. Paeonol attenuated CUMS-induced depression-like behaviors, which were accompanied by hippocampal neuronal morphological alterations. After Paeonol treatment for 4weeks, the dendritic length and complexity and the density of dendritic spines markedly increased in the hippocampal CA1 and the dentate gyrus (DG). However, CUMS or Paeonol treatment does not selectively affect dendritic spine types. Simultaneously, administration of Paeonol deterred CUMS-induced cofilin1 activation that is essential for remolding of dendritic spines. The induction of CUMS downregulated BDNF levels and upregulated Rac1/RhoA levels; however, the tendency of these was inhibited by treatment with Paeonol. Our data suggest that BDNF-Rac1/RhoA pathway may be involved in attenuation of CUMS-induced behavioral and neuronal damage by Paeonol that may represent a novel therapeutic agent for depression.

Subspinal impingement: clinical outcomes of arthroscopic decompression with one year minimum follow up.

This study was designed to (1) evaluate the clinical outcomes after arthroscopic subspinal decompression in patients with hip impingement symptoms and low AIIS, and to (2) assess the presence of low anterior inferior iliac spine on the pre-operative radiographs of patients with established subspinal impingement diagnosed intra-operatively. Retrospective analysis of patients who underwent arthroscopic subspinal decompression has been performed. The indications for surgery were femoroacetabular impingement (FAI), or subspinal impingement. Pre-operative radiographs were assessed for anterior inferior iliac spine type. Intra-operative diagnosis of low anterior inferior iliac spine was based on the level of anterior inferior iliac spine extension relative to the acetabulum and the presence of reciprocal labral and chondral lesions. In patients where low anterior inferior iliac spine was not diagnosed on pre-operative radiographs, the pre-operative radiographs were re-read retrospectively to assess missed signs of low anterior inferior iliac spine. Thirty-four patients underwent arthroscopic subspinal decompression between 2012 and 2015. The patients were followed for a median of 25months (13-37months). Intra-operatively, grade 2 anterior inferior iliac spine was found in 27 patients and grade 3 anterior inferior iliac spine was found in 7 patients. MHHS, HOS, and HOSS scores increased from median (range) pre-operative scores of 55 (11-90), 48 (20-91) and 20 (0-80) to 95 (27-100), 94 (30-100) and 91 (5-100), respectively (p < 0.0001, p = 0.001, p < 0.0001, respectively). Pre-operative diagnosis of low AIIS was made in 6/34 patients via AP radiographs. On retrospective analysis of pre-operative radiographs, signs of low AIIS were still not observed in 21/34 (61.8%) patients. Arthroscopic subspinal decompression of low AIIS yielded significantly improved outcome measures and high patient satisfaction at a minimum of 13months follow-up. Low AIIS is often under-diagnosed on AP pelvis and lateral frog radiographs and if left untreated, may result in unresolved symptoms and failed procedure. IV.

S193. EX VIVO SIGNATURE OF PSYCHOSIS AND TREATMENT RESPONSE IN PATIENT-DERIVED NEURONS

BackgroundPostmortem studies in schizophrenia show well-replicated neuronal differences in the prefrontal cortex (PFC), specifically showing lower dendritic spine density in upper-layer cortical pyramidal neurons. Animal models that recapitulate features of psychosis also show lower dendritic spine density and synapse number in the PFC, with a more pronounced effect in upper-layer cortical neurons. Furthermore, the decrease in dendritic spines and synapses in animal models have been shown to be reversible with antipsychotic treatment. Results from postmortem brains, animal models and in vitro rodent cultures provide a strong impetus to test the hypothesis that dendritic spine biology plays an important role in the biology of schizophrenia and in mediating the effects of antipsychotic medications.MethodsTo extend these findings, we studied cortical neurons generated from subjects with schizophrenia. We reprogrammed induced pluripotent stem cells (iPSCs) from human subjects with schizophrenia and from matched healthy controls. We differentiated human iPSCs along the forebrain lineage to generate mature cortical neurons. We developed a robust experimental approach to delineate and quantify spines in the dendrites as well as methods to outline and measure the spines in order to classify the different spine types. We also developed methodology for functional characterization of individual neurons using calcium imaging in the cortical neuron cultures.ResultsWe found that cortical neurons generated from the iPSCs of schizophrenia patients had a lower density of dendritic spines when compared to cortical neurons generated from the iPSCs of healthy control subjects. We also delineated the different composition of spine types in cortical neurons from schizophrenia patients when compared to those from healthy control subjects. In cortical neurons from schizophrenia subjects, we found that clozapine exposure in vitro leads to a robust increase in dendritic spine density.DiscussionWe found that cortical neurons from iPSCs of schizophrenia subjects recapitulate the dendritic spine differences reported in postmortem brains of schizophrenia subjects. Moreover, we found that human cortical neurons from schizophrenia subjects show increased dendritic spine density when exposed in vitro to clozapine. The ability to delineate cellular features related to disease biology in iPSC-derived neurons opens the door to understand the pathophysiology of schizophrenia and lay the foundations for the development of novel therapeutics.

The Impact of Selected Aspects of Life on the Incidence of Back Pain in Relation to Age of Patients

&lt;b&gt;Intodruction:&lt;/b&gt; The most common reasons for back pain in modern society include inadequate physical activity, obesity and lack of basic knowledge on the correct positions of the spine. There are also other reasons such as pathological changes including damage and degeneration of annular fibers in the spinal disk, posttraumatic back pain and incorrect posture. &lt;br/&gt;&lt;b&gt;Materials and methods:&lt;/b&gt; On the basis of a survey study on the population of 240 individuals (120 males and 120 females) we aimed to answer the following questions: how body index, physical activity, type of profession and education level correlate with the frequency of back pain in relation to age. Furthermore, responders reported the most commonly injured spine regions and types of treatments. &lt;br/&gt;&lt;b&gt;Results and Conclusions:&lt;/b&gt; Obese individuals more often suffer from back pain. Moderate physical activity is beneficial on spine prophylaxis. Aging correlates with higher risk of back pain. Back pain is the most commonly reported in the lumbar region. Common painkiller medications and restricted physical activity represent main treatments of back pain. Visiting a doctor, physiotherapy and therapeutic massage are less common. These conclusions hold true for both males and females.