Ipsilateral Rotation Research Articles

Hydroxytyrosol inhibits MAO isoforms and prevents neurotoxicity inducible by MPP+ invivo.

Parkinson's disease is considered to be due to an increase in the catabolism of dopamine by the action of monoamine oxidase (MAO) enzymes which leads to an increase in reactive oxygen species (ROS) and loss of dopaminergic neurons. Here, in a model of neurotoxicity inducible by 1-methyl-4-phenylpyridinium (MPP+), we tested the effect of hydroxytyrosol (HTy), a potent antioxidant, on generation of ROS. Five minutes after a single intravenous administration of 1.5 mg/Kg of Hty, Wistar rats received an intrastriatal micro-injection of 10 micrograms of MPP+ while control animals received saline solution. Six days later, all animals were treated with apomorphine (1 mg/Kg), subcutaneously and ipsilateral rotations were assessed within an hour. Then, the rats were sacrificed, striatal tissues were removed and their catecholamines and MAO-A and B activities were quantitated. Pretreatment with HTy significantly diminished the number of ipsilateral rotations. This recovery correlated with significant preservation of striatal dopamine and significant inhibition of of the MAO activity. These results are consistent with the inhibitory effect of HTy on the MAO isoforms and form a basis for the neuroprotective mechanism of this phenylpropanoid in MPP+ induced Parkinson's disease.

Alterations of the gut microbiota with antibiotics protects dopamine neuron loss and improve motor deficits in a pharmacological rodent model of Parkinson's disease

Parkinson's disease (PD) is a debilitating condition resulting in motor and non-motor symptoms affecting approximately 10 million people worldwide. Currently, there are no pharmacological treatments that can cure the condition or effectively halt its progression. The focus of PD research has been primarily on the neurobiological basis and consequences of dopamine (DA) neuron degeneration given that the loss of DA neurons projecting from the substantia nigra to the dorsal striatum results in the development of cardinal PD motor symptoms. Alternatively, gastrointestinal dysfunction is well recognized in PD patients, and often occurs prior to the development of motor symptoms. The gut microbiota, which contains thousands of bacterial species, play important roles in intestinal barrier integrity and function, metabolism, immunity and brain function. Pre-clinical and clinical studies suggest an important link between alterations in the composition of the gut microbiota and psychiatric and neurological conditions, including PD. Several reports have documented gut dysbiosis and alterations in the composition of the gut microbiota in PD patients. Therefore, the goal of this study was to explore the contribution of the gut microbiota to the behavioral and neurochemical alterations in a rodent toxin model of DA depletion that reproduces the motor symptoms associated with PD. We observed that chronic treatment of adult rats with non-absorbable antibiotics ameliorates the neurotoxicity of 6-hydroxydopamine (6-OHDA) in a unilateral lesion model. Specifically, immunohistochemistry against the dopaminergic neuron marker tyrosine hydroxylase (TH) showed an attenuation of the degree of 6-OHDA-induced dopaminergic neuron loss in antibiotic treated animals compared to control animals. In addition, we observed a reduction in the expression of pro-inflammatory markers in the striatum of antibiotic-treated animals. The degree of motor dysfunction after 6-OHDA was also attenuated in antibiotic-treated animals as measured by paw-rearing measurements in the cylinder test, forepaw stepping test, and ipsilateral rotations observed in the amphetamine-induced rotation test. These results implicate the gut microbiota as a potential contributor to pathology in the development of PD. Further studies are necessary to understand the specific mechanisms involved in transducing alterations in the gut microbiota to changes in dopaminergic neuron loss and motor dysfunction.

Local and Widespread Pressure Pain Hyperalgesia Is Not Side Specific in Females with Unilateral Neck Pain that Can Be Reproduced during Passive Neck Rotation.

Current evidence for widespread hyperalgesia in non-specific neck pain (NSNP) is unclear. It is currently recommended to group NSNP patients according to pain-provoking movements. The aim of this study was to investigate local and widespread pain sensitivity in females with unilateral NSNP that is reproducible during passive neck rotation compared with matched controls, and to compare the side specific effect of pain location on pressure pain sensitivity among females with unilateral NSNP. Thirty-six females with unilateral NSNP evoked during passive ipsilateral (n = 20) or contralateral (n = 16) rotation toward the painful side were compared with 20 controls. Participants reported their pain intensity at rest and during passive neck rotation and completed the Neck Disability Index. Pressure pain thresholds (PPTs) were assessed bilaterally over the anterior scalene; the sternocleidomastoid; the levator scapulae; lateral to the spinous process of C6; the median, ulnar, and radial nerves; and the tibialis anterior. The ANOVA revealed lower PPTs in females with unilateral NSNP compared with the controls (all at p < 0.001), but no differences were found between the sides, nor was there any Group × side interaction. Among females with NSNP, those with higher pain intensity during ipsilateral rotation toward the painful side showed lower PPTs over the anterior scalene, median nerve, ulnar nerve, and tibialis anterior (all, p < 0.05) than females with higher pain intensity during contralateral rotation toward the painful side. These findings demonstrated bilateral local and widespread pressure pain hyperalgesia in females with unilateral NSNP that was reproducible during passive neck rotation compared with controls. There was no side specific effect of pain location on PPTs among females with unilateral NSNP.

Dereplication of Components Coupled with HPLC-qTOF-MS in the Active Fraction of Humulus japonicus and It's Protective Effects against Parkinson's Disease Mouse Model.

Humulus japonicus is an annual plant belonging to the Cannabacea family, and it has been traditionally used to treat pulmonary tuberculosis, dysentery, chronic colitis, and hypertension. We investigated the active components against Parkinson’s disease from H. japonicus fraction (HJF) using high performance liquid chromatography (HPLC) coupled with quadruple-time-of-flight mass spectroscopy (qTOF-MS) and NMR. Fourteen compounds were isolated from HJF, including one new compound, using HPLC-qTOF-MS and NMR. The major compounds of HJF were luteolin-7-O-glucoside and apigenin-7-O-glucoside, and there was approximately 12.57- and 9.68-folds increase in the contents of these flavonoids compared to those of the 70% EtOH extract. Apigenin and luteolin exhibited the strongest inhibitory effects on monoamine oxidase (MAO) B enzyme activity. In animal studies, limb-use behavior was significantly reduced by unilateral 6-OHDA lesion and ipsilateral rotations. These results indicated that oral administration of 300 mg/kg HJF resulted in the improvement of motor asymmetry and motor impairment in unilateral 6-OHDA-lesioned mice. HJF, including active components leads to an improvement of motor behavior in a Parkinson’s disease mouse model.

A new variant ligament of the atlantooccipital joint: the lateral oblique atlantooccipital ligament.

During routine dissection of the anterior craniocervical junction (CCJ), a variant ligament just anterior to the articular capsule of the atlantooccipital joint was observed. To our knowledge, no literature has previously described this ligament. Therefore, the aim of this study was to clarify the anatomy, incidence, and biomechanics of this undescribed structure of the anterior atlantooccipital joint. Twenty-six sides from 13 fresh-frozen adult cadavers were used for this study and the morphology of the variant ligament examined. When present, its length, width, thickness, and the angle from the midline of the CCJ were measured. The variant ligament identified, when present, is distinct and located anterior to the atlantooccipital joint capsule traveling between the occipital bone and the transverse process of the atlas. The ligament was found on 12 of 26 sides (46.2%). The mean length of the ligament was 32.0 ± 5.5mm. The ligament became taut with contralateral lateral flexion and the ipsilateral rotation of the atlantooccipital joint. We propose that this ligament may be termed the lateral oblique atlantooccipital ligament. To date, this structure has not been described in any textbooks or reports in the extant medical literature. Although its function is not clear, based on its course and connections, it might function as a secondary stabilizer of the atlantooccipital joint. As the stability of the craniocervical junction is of paramount importance, knowledge of normal and variant anatomical structures in this region is important for the surgeon treating patients with pathology of this region. These slides can be retrieved under Electronic Supplementary Material.

Effects of the trunk position on muscle stiffness that reflects elongation of the lumbar erector spinae and multifidus muscles: an ultrasonic shear wave elastography study.

The present study aimed to clarify the effects of the trunk position on muscle stiffness that reflects elongation of the lumbar erector spinae and lumbar multifidus muscles using ultrasonic shear wave elastography (SWE). The study included ten healthy men. The shear elastic modulus of the left lumbar erector spinae and lumbar multifidus muscles were evaluated using ultrasonic SWE. Measurement postures for the left lumbar erector spinae muscle were (1) prone position (Rest), (2) sitting position with the trunk flexed (Flexion), (3) the Flexion position adding right trunk lateral flexion (Flexion-Lateral Flexion), and (4) the Flexion position adding right trunk rotation (Flexion-Rotation 1). The left lumbar multifidus muscle were measured in positions (1)-(3), and (5) the Flexion position adding left trunk rotation (Flexion-Rotation 2). The shear elastic modulus of the lumbar erector spinae muscle in the Flexion-Lateral Flexion position was significantly higher than that in the Rest, Flexion, or Flexion-Rotation 1 positions. Shear elastic modulus of the lumbar multifidus muscle was similar in the Flexion, Flexion-Lateral Flexion, and Flexion-Rotation 2 positions, but significantly lower in the Rest position. The results of the present study suggest that the lumbar erector spinae muscle is stretched effectively in the position adding trunk contralateral lateral flexion to flexion. The results also indicate that the lumbar multifidus muscle, which does not appear to be affected by adding trunk contralateral lateral flexion or ipsilateral rotation to flexion, is stretched effectively in the trunk flexion position.

Comparative effect of driving side on low back pain due to Repetitive Ipsilateral Rotation.

Objective:To determine the effects of repetitive ipsilateral rotation on low back pain among the taxi drivers of right and left hand drive.Methods:A total of 1200 (600 Iran+600 Pakistan) male taxi drivers, aged between 20-60 years with work experience of more than one year were randomly selected and interviewed in Tehran (Iran) & Lahore (Pakistan) to fill self-administered questionnaires in Persian and Urdu languages which contained socio-demographic, work related and LBP characteristics. Chi-square test and multiple logistic regression models were employed for statistical analyses.Results:Point, one week, one year and lifetime prevalence of LBP among right hand drive taxi drivers was 26.7%, 35.5%, 49.8% and 77.7% respectively. Point, one week, one year and lifetime prevalence of LBP among left hand drive taxi drivers was 37%, 42.7%, 53.5% and 72.3% respectively. Mean Numeric Pain rating scale (NPRS) score was 4.15 (SD=1.42) in Pakistan, while in Iran it was 4(SD=1.57). There was no significant difference regarding pain intensity (p=0.123) between drivers from both countries. Mean Roland-Morris Questionnaire (RMQ) score among drivers in Pakistan with LBP was 7.76(SD= 2.50), while in Iranian drivers who had LBP, mean RMQ score was 7.71(SD=2.99).Conclusion:Static or less dynamic muscles are more prone to LBP due to lower endurance. Lack of exercising habit, work as a driver for more number of years, driving within city, more driving hours in a day, forward bending, lifting, no seat comfort, lack of awareness regarding ergonomics and lower satisfaction level of job were the main reasons of LBP.

Multifidus muscle size changes at different directions of head and neck movements in females with unilateral chronic non-specific neck pain and healthy subjects using ultrasonography

ObjectiveThe aim of the study was to compare the dimensions of cervical multifidus muscle (CMM) in different conditions. MethodsTwenty five women with neck pain and 25 healthy subjects participated in this study. The dimensions of the CMM were measured at rest, 50% and 100% maximum isometric voluntary contraction (MIVC) at six directions of neck movements, using ultrasonography. ResultsThe size of multifidus was smaller in patients than healthy individuals at rest state (P < 0.05). A significant smaller CMM dimension was found in the affected side compared with unaffected side in patients group (P < 0.05). The result of ANOVA for MLD showed a significant difference for contraction levels (P < 0.001) and neck movements (P < 0.001) in both groups. The MLD of the CMM was significantly different between CMM at rest and 50%, and 100% MIVC (P < 0.001). No significant differences were found between the groups at 50% and 100% MIVC (P > 0.05 in both instances). The most prominent CMM size change was observed during neck extension, flexion, ipsilateral lateral-flexion, and ipsilateral rotation, respectively (P < 0.05). ConclusionsResults of the present study indicate that the size of CMM was decreased in patients with neck pain in rest state. The size of CMM changes in all directions of neck movements, although the most prominent was during neck extension. This points out CMM stabilization role's in different directions of neck movements.

Effects of vestibular disorders on vestibular reflex and imagery.

The aim of this study was to establish the effect of vestibular lesion on vestibular imagery. Subjects were required to estimate verbally their passively travelled rotation angles in complete darkness, i.e., to activate vestibular imagery. During motion, the vestibulo-ocular reflex (VOR) was measured. Thus, we examined the coherence between the vestibulo-ocular reflex and self-rotation imagery, with vestibular-lesioned patients and healthy participants. Unilateral acute and chronic patients, bilateral patients, and healthy subjects were compared. The stimulus was a sequence of eight successive passive rotations, with four amplitudes (from 90° to 360°) in two directions. The VOR gain was lower in patients with unilateral lesions, for ipsilateral rotations. The healthy subjects had the highest gain and the bilateral group the lowest, on both rotation sides. Thanks to vestibular compensation after acute unilateral neuritis, the VOR gain increased in lesion side and decreased in healthy side, resulting in a similar gain in both sides. A deficit of vestibular imagery was found exclusively in patients with bilateral hyporeflexia, on both sides. The performance in vestibular imagery was good in the control group and correct in the unilateral patients. Finally, we found a significant correlation between the efficiency of the VOR and that of vestibular imagery, exclusively in the bilateral patients. The present study shows the complex relationship between vestibular imagery and the VOR. This imagery test contributes to another assessment of the spatial handicap of vestibular patients. It seems particularly interesting for patients with bilateral canal paresis and could be used to confirm this diagnosis.

Biomechanical Evaluation of Unilateral Versus Bilateral C1 Lateral Mass-C2 Intralaminar Fixation.

Study Design:Biomechanical, cadaveric study.Objectives:To compare the relative stiffness of unilateral C1 lateral mass-C2 intralaminar fixation to intact specimens and bilateral C1 lateral mass-C2 intralaminar constructs.Methods:The biomechanical integrity of a unilateral C1 lateral mass-C2 intralaminar screw construct was compared to intact specimens and bilateral C1 lateral mass-C2 intralaminar screw constructs. Five human cadaveric specimens were used. Range of motion and stiffness were tested to determine the stiffness of the constructs.Results:Unilateral fixation significantly decreased flexion/extension range of motion compared to intact (P < .001) but did not significantly affect axial rotation (P = .3) or bending range of motion (P = .3). There was a significant decrease in stiffness in extension for both unilateral and bilateral fixation techniques compared to intact (P = .04 and P = .03, respectively). There was also a significant decrease in stiffness for ipsilateral rotation for the unilateral construct compared to intact (P = .007) whereas the bilateral construct significantly increased ipsilateral rotation stiffness compared to both intact and unilateral fixation (P < .001).Conclusion:Bilateral constructs did show improved biomechanical properties compared to the unilateral constructs. However, unilateral C1-C2 fixation using a C1 lateral mass and C2 intralaminar screw-rod construct decreased range of motion and improved stiffness compared to the intact state with the exception of extension and ipsilateral rotation. Hence, a unilateral construct may be acceptable in clinical situations in which bilateral fixation is not possible, but an external orthosis may be necessary to achieve a fusion.

The significance of rotational behavior and sensitivity of striatal dopamine receptors in hemiparkinsonian rats: A comparative study of lactacystin and 6-OHDA

A growing body of evidence indicates that impairment of the ubiquitin–proteasome (UPS) system in the substantia nigra (SN) plays an important role in the pathogenesis of Parkinson’s disease (PD). The aim of our study was to compare two unilateral rat models, one produced by intranigral administration of the UPS inhibitor lactacystin or the other induced by 6-OHDA, in terms of their effect on the amphetamine- and apomorphine-induced rotational behavior, striatal dopamine (DA) D1 and D2 receptor sensitivity and tissue levels of DA and its metabolites. We found that these models did not differ in the intensity of ipsilateral rotations induced by amphetamine. In contrast, apomorphine produced contralateral rotations only in 6-OHDA-lesioned rats, and, depending on the dose, it induced either no or moderate ipsilateral rotations in the lactacystin-lesioned group. In addition, lactacystin induced a strong reduction in the tissue DA level and its metabolites in the lesioned striatum and SN when measured three weeks after the administration which was aggravated six weeks post-lesion, reaching the level comparable to the 6-OHDA group. Binding of [3H]raclopride to D2 receptors was increased in the lesioned striatum in both investigated (PD) models six weeks after lesion. In turn, binding of [3H]SCH23390 to the striatal D1 receptors was not changed in the lactacystin group but was increased bilaterally in the 6-OHDA group. The present results add a new value to the study of DA receptor sensitivity and are discussed in the context of the validity of the lactacystin model as a suitable model of Parkinson’s disease.

α4 nicotinic acetylcholine receptor modulated by galantamine on nigrostriatal terminals regulates dopamine receptor-mediated rotational behavior

Galantamine, an acetylcholine esterase (AChE) inhibitor used to treat dementia symptoms, also acts as an allosteric potentiating ligand (APL) at nicotinic acetylcholine receptors (nAChRs). This study was designed to evaluate the allosteric effect of galantamine on nAChR regulation of nigrostrial dopaminergic neuronal function in the hemiparkinsonian rat model established by unilateral nigral 6-hydroxydopamine (6-OHDA) injection. Methamphetamine, a dopamine releaser, induced ipsilateral rotation, whereas dopamine agonists apomorphine (a non-selective dopamine receptor agonist), SKF38393 (a selective dopamine D1 receptor agonist), and quinpirole (a selective dopamine D2 receptor agonist) induced contralateral rotation. When 6-OHDA-injected rats were co-treated with nomifensine, a dopamine transporter inhibitor, a more pronounced and a remarkable effect of nicotine and galantamine was observed. Under these conditions, the combination of nomifensine with nicotine or galantamine induced the ipsilateral rotation similar to the methamphetamine-induced rotational behavior, indicating that nicotine and galantamine also induce dopamine release from striatal terminals. Both nicotine- and galantamine-induced rotations were significantly blocked by flupenthixol (an antagonist of both D1 and D2 dopamine receptors) and mecamylamine (an antagonist of nAChRs), suggesting that galantamine modulation of nAChRs on striatal dopaminergic terminals regulates dopamine receptor-mediated movement. Immunohistochemical staining showed that α4 nAChRs were highly expressed on striatal dopaminergic terminals, while no α7 nAChRs were detected. Pretreatment with the α4 nAChR antagonist dihydroxy-β-erythroidine significantly inhibited nicotine- and galantamine-induced rotational behaviors, whereas pretreatment with the α7 nAChR antagonist methyllycaconitine was ineffective. Moreover, the α4 nAChR agonist ABT-418 induced ipsilateral rotation, while the α7 nAChR agonist PNU282987 had no significant effect on rotational behavior. These results suggest that galantamine can enhance striatal dopamine release through allosteric modulation of α4 nAChRs on nigrostriatal dopaminergic terminals.

The Effects of the Position of Ipsilateral Neck Rotation on the Inhibition of the Upper Trapezius Muscle During Lower Trapezius Exercises

Background: The unilateral prone arm lift (UPAL) is commonly used to exercise the lower trapezius muscle. However, overactivation of the upper trapezius can induce pain during UPAL exercises in subjects with upper trapezius tenderness. Objects: The purpose of this study was to investigate the effects of position of ipsilateral neck rotation (INR) on the inhibition of upper trapezius muscle activity and the facilitation of the lower trapezius muscle when performing UPAL exercises. Methods: In total, 19 subjects with upper trapezius tenderness were recruited for the study. Electromyographic (EMG) activity was measured in the upper, middle, and lower trapezius muscles during UPAL with and without INR position. Wilcoxon signed-rank test was used to compare EMG activity in the trapezius muscles and the muscle ratios. Results: EMG activity in the upper trapezius muscles was decreased significantly in the INR condition compared to without the position with INR during UPAL exercises (p .05). However, the ratio of lower to upper trapezius activation showed a significant increase in the INR condition compared to the without INR condition (p<.05), indicating greater lower trapezius activation relative to the upper trapezius in the INR position than in the without INR position. Conclusions: The EMG results obtained in this study suggest that the position with INR reduced overactivation in the upper trapezius and improved muscle imbalance during lower trapezius exercises in individuals with upper trapezius tenderness.

CART modulates the effects of levodopa in rat model of Parkinson’s disease

Parkinson’s disease (PD) is an age-related disorder characterized by a progressive degeneration of dopaminergic neurons of substantia nigra (SN). The neuropeptide cocaine- and amphetamine-regulated transcript (CART) is known to closely interact with the dopamine system and regulate psychomotor activity. We screened the effectiveness of CART in reversing the symptoms of PD in a rat model. PD like condition was induced by administering 6-hydroxydopamine (6-OHDA) directly in the SN of the right side. Fifteen days later, intraperitoneal (IP) treatment with apomorphine hydrochloride to these rats, resulted in contralateral rotations in the rotation test chamber suggesting induction of PD-like symptoms. This action of apomorphine was significantly attenuated by intracerebroventricular (ICV) treatment with CART and potentiated by CART antibody. IP treatment with levodopa also produced contralateral rotation in PD induced rats, and showed anti-Parkinson-like action. Prior treatment with CART via ICV route potentiated the anti-Parkinsonian effects of levodopa, while CART antibody produced opposite effects. CART treatment per se, to PD induced rats produced ipsilateral rotations, suggesting that the peptide may promote the endogenous release of dopamine from intact neurons. While CART-immunoreactivity in arcuate nucleus, paraventricular nucleus, striatum, substantia nigra, ventral tegmental area and locus coeruleus was reduced in the PD induced rats, levodopa treatment restored the expression of CART-immunoreactivity in these nuclei. These results suggest that endogenous CART might closely interact with the dopamine containing SN-striatal pathway which is known to profoundly influence the motor system. The study underscores the importance of CART as a potential therapeutic agent in the treatment of PD.

Relationship between spinal range of motion and trunk muscle activity during trunk rotation.

[Purpose] The aim of this study was to clarify the relationship between spinal range of motion and trunk muscle activity during trunk rotation using a three-dimensional motion analysis system and surface electromyography. [Subjects and Methods] The subjects comprised 11 healthy men. A three-dimensional motion analysis system measured the trunk rotational angle of 4 segments of the thoracic vertebrae and 2 segments of the lumbar vertebrae. Surface electromyography measured the activities of the unilateral latissimus dorsi, lumbar multifidus, rectus abdominis, external oblique, internal oblique, and transversus abdominis muscles. [Results] During ipsilateral rotation at thoracic vertebral levels, the muscle activity of the latissimus dorsi and external oblique was significantly increased compared with the activity in the 0–10% range of trunk rotation. During early ipsilateral rotation at lumbar vertebral levels, the muscle activity of the internal oblique and transversus abdominis was significantly increased compared with that in the 0–10% range of trunk rotation. During contralateral rotation at both thoracic and lumbar vertebral levels, the muscle activity of the external oblique was significantly increased compared with that in the 0–10% range of trunk rotation. [Conclusion] This study indicates that it is important to consider vertebral segments and spinal range of motion during trunk rotation.

Chronic low-dose melatonin treatment maintains nigrostriatal integrity in an intrastriatal rotenone model of Parkinson’s disease

Parkinson׳s disease is a major neurodegenerative disorder which primarily involves the loss of dopaminergic neurons in the substantia nigra and related projections in the striatum. The pesticide/neurotoxin, rotenone, has been shown to cause systemic inhibition of mitochondrial complex I activity in nigral dopaminergic neurons, with consequent degeneration of the nigrostriatal pathway, as observed in Parkinson׳s disease. A novel intrastriatal rotenone model of Parkinson׳s disease was used to examine the neuroprotective effects of chronic low-dose treatment with the antioxidant indoleamine, melatonin, which can upregulate neurotrophic factors and other protective proteins in the brain. Sham or lesioned rats were treated with either vehicle (0.04% ethanol in drinking water) or melatonin at a dose of 4µg/mL in drinking water. The right striatum was lesioned by stereotactic injection of rotenone at three sites (4μg/site) along its rostrocaudal axis. Apomorphine administration to lesioned animals resulted in a significant (p<0.001) increase in ipsilateral rotations, which was suppressed by melatonin. Nine weeks post-surgery, animals were sacrificed by transcardial perfusion. Subsequent immunohistochemical examination revealed a decrease in tyrosine hydroxylase immunoreactivity within the striatum and substantia nigra of rotenone-lesioned animals. Melatonin treatment attenuated the decrease in tyrosine hydroxylase in the striatum and abolished it in the substantia nigra. Stereological cell counts indicated a significant (p<0.05) decrease in dopamine neurons in the substantia nigra of rotenone-lesioned animals, which was confirmed by Nissl staining. Importantly, chronic melatonin treatment blocked the loss of dopamine neurons in rotenone-lesioned animals. These findings strongly support the therapeutic potential of long-term and low-dose melatonin treatment in Parkinson׳s disease.

A 64-year old woman with right hand swelling and paresthesia

A 64-year old woman presented to the emergency department with a 6-month history of right lateral cervical pain and a 2-week history of erythema and swelling of her right hand and wrist, accompanied by a tingling sensation alongher right forearm. The patient denied recent occurrence of fever, recent trauma, or strenuous exercise. She appeared comfortable. Her temperature was 36.2 °C, blood pressure was 132/ 70mmHg, pulsewas 89 beats/minute andO2 saturationwas 98% in ambient room air. Physical examination of the right upper limb revealed mild erythema and non-pitting edema of the hand and wrist as well as decreased sensation to light touch and pain along the C8–T1 dermatomes. Motor strength in all muscle groups and deep tendon reflexes remained intact. Loss of the radial pulse during inspiration was noted upon ipsilateral rotation of the head during neck extension. Examination of the rest of the neck, left arm and lower limbs was normal. Laboratory work-up including complete blood count, erythrocyte sedimentation rate, and C-reactive protein was within the normal limits. A posterior–anterior chest roentgenogram was obtained (Fig. 1).

454. Prior AAV2-hIL10 Infusion Decreases AAV9-Dependent Immunotoxicity in Rat Brain

Cerebral infusion of AAV9 vectors encoding non-self proteins results in the initiation of a robust immune reaction at the site of injection due to the vector's ability to transduce antigen-presenting cells in the brain [1]. Infusion of AAV9 encoding a human gene, aromatic L-amino acid decarboxylase (hAADC), elicited an initial innate immune activation at the site of infusion that was succeeded by a robust adaptive immune response that included generation of hAADC antibodies, lymphocytic infiltration and cell-mediated elimination of transduced cells in the brain. In this study, we investigated whether the potent anti-inflammatory cytokine, human interleukin-10 (hIL10) could suppress this immune response. Four weeks prior to unilateral infusion of AAV9-hAADC into rat striatum, we infused AAV2-hIL10 bilaterally into striatum (control rats received bilaterally injection of AAV2-GFP). Six weeks after AAV9-hAADC injection, control rats revealed robust amphetamine-induced ipsilateral rotational behavior (956±203 (S.D.) turns/1 hour). In while, in AAV2-hIL10-treated rats ipsilateral rotations were reduced by 66 % compared with control rats and this effect persisted for at least 8 weeks. This neuroprotective effect of hIL10 was evident histologically. The number of surviving neurons (NeuN) was significantly increased in AAV2-hIL10-treated animals compared to AAV2-GFP-treated controls, and microglial and astrocytic activation was diminished. Whereas, in control rats, a significant number of hAADC-positive astrocytes was observed (GFAP/hAADC double fluorescent staining), astrocytic transduction in AAV2-hIL10-treated rats was almost completely suppressed. This somewhat puzzling result may be due to an effect of IL10 on astrocytic expression of an AAV9 receptor required for transduction. However, our findings suggest that expression of IL-10 in the brain may be a useful adjunctive therapy in the treatment of neurological diseases in which the expression of a foreign antigen is unavoidable.

P156 – 2357: Torticollis: Different etiologic conditions in childhood

Objective Torticollis is an abnormal head posture that occurs at all ages, seen in childhood with an estimated incidence of 1.3%. Clinical presentation includes ipsilateral tilt and controlateral rotation and translation. The purpose of this studyis to better understand the spectrum of disease in torticollis except congenital muscular torticollis. Methods 17 patients presented with complaints of twisted neck, neck pain, weakness of extremity, esotropia and gait disorder between May 2012 and November 2014 were enrolled in this study. Cranial and/or spinal MR, CT imaging, ultrasound and ph meter studies were performed in order to reveal etiology. Results Nine patient underwent surgery, two patientes received medical therapy for reflux and benign paroxysmal torticollis. For six patients only clinical follow-up was sufficient. Conclusion There is a wide differential diagnosis for a patient with torticollis, not just neurological in etiology which should be considered in any patient with torticollis. Moreover, early diagnosis of etiological disease will reduce mortality and morbidity. Therefore, clinicians managing children with torticollis must be vigilant about underlying neurological complications.

Activity of serotonin 5-HT1A receptor ‘biased agonists’ in rat models of Parkinson's disease and l-DOPA-induced dyskinesia

Serotonin 5-HT1A receptor agonists reduce l-DOPA-induced dyskinesia (LID) in animal models of Parkinson's disease (PD). Here, we compared the effects of novel 5-HT1A receptor ‘biased agonists’ on LID in hemiparkinsonian rats. F13714 preferentially activates pre-synaptic 5-HT1A autoreceptors. F15599 preferentially activates cortical postsynaptic 5-HT1A heteroreceptors. The partial agonist, tandospirone, does not differentiate these receptor subpopulations. The drugs were also tested on rotational behavior, rotarod and cylinder test for evaluation of locomotor activity, motor coordination and forelimb akinesia. Finally, the effects of F13714 and F15599 on 5-HT, DA, glutamate, and GABA release were investigated by microdialysis.F13714 abolished l-DOPA-induced AIMs even at very low doses (0.02–0.04 mg/kg). This effect was reversed by the selective 5-HT1A receptor antagonist, WAY100635. F13714 also elicited ipsilateral rotations (which were blocked by WAY100635) and potentiated the rotational activity of a sub-threshold dose of l-DOPA (2 mg/kg). F13714 profoundly inhibited striatal 5-HT release on both sides of the brain, and slightly increased DA release on the intact side. F15599 inhibited the l-DOPA-induced AIMs only at a dose (0.16 mg/kg) that reduced 5-HT release. Tandospirone produced a modest attenuation of peak AIMs severity and did not elicit rotations. F13714, F15599 and tandospirone did not modify the action of l-DOPA in the cylinder test but impaired rotarod performance at the highest doses tested.Targeting 5-HT1A receptors with selective biased agonists exerts distinct effects in the rat model of PD and LID. Preferential activation of 5-HT1A autoreceptors could potentially translate to superior antidyskinetic and l-DOPA dose-sparing effects in PD patients.