Locomotion In Open Field Test Research Articles

Zidovudine reduces ketamine-induced psychotic symptoms in mice

Introduction: Infection with human immuno-deficiency virus (HIV) is associated with several neurological disorders including psychotic symptoms. Treatment or therapeutic management of these symptoms with conventional anti-psychotic drugs (APDs) is associated with drug-drug interaction and side effects that may cause treatment failure. Zidovudine (AZT) an anti-retroviral (ARV) drug, is a nucleoside analogue reverse transcriptase inhibitor (NRTI) with highest CNS penetrating ability, but few or nothing is known about its CNS effects.
 Objective of study: To evaluate the effect of AZT on ketamine-induced depression, hyperkinesia, and cognitive function in mice.
 Method: Acute toxicity was conducted for oral and intraperitoneal administration using Lorke’s (1983) method. Acute zidovudine alone and its concurrent (AZT + Ketamine) sub-chronic (7 days) administration was investigated using forced swim test, open field locomotor test and Y-maze test. Olanzepine (5mg/kg), Haloperidol (1 mg/kg) and Eserine (0.03 mg/kg) were used as standard controls respectively with saline as normal control. Eserine was administered intraperitoneal 30 minutes before the test, while the 5 tested zidovudine doses (12.5, 25, 50, 100 and 200 mg/kg) were administered singly orally for 60 minutes prior to the acute test while ketamine 30mg/kg intraperitoneal administered concurrently for 7 days for the sub-chronic test
 Result: The LD50 for oral and intraperitoneal administration were determined to be 3807.88 mg/kg and 2154 mg/kg respectively. Concurrent AZT administration with ketamine for 7 days, significantly (p<0.001) reduced immobility time at AZT doses of 25 mg/kg and 12.5 mg/kg compared to the control. The 7-days AZT concurrent treatments with ketamine reduced locomotion at all AZT test groups, compared to normal control group. The mean percent alternation was severely reduced in acute AZT treatments, but increased in concurrent AZT-ketamine administration.
 Conclusion: AZT ameliorate ketamine-induced psychotic-like symptoms in mice, but was found to cause cognitive deficits in normal controls.

A custom-made weight-drop impactor to produce consistent spinal cord injury outcomes in a rat model.

The main objective of this study is to design a custom-made weight-drop impactor device to produce a consistent spinal cord contusion model in rats in order to examine the efficacy of potential therapies for post-traumatic spinal cord injuries (SCIs). Adult female Sprague-Dawley rats (n = 24, 11 weeks old) were randomly divided equally into two groups: sham and injured. The consistent injury pattern was produced by a 10 g stainless steel rod dropped from a height of 30 mm to cause (0.75 mm) intended displacement to the dorsal surface of spinal cord. The neurological functional outcomes were assessed at different time intervals using the following standardized neurobehavioral tests: Basso, Beattie, and Bresnahan (BBB) scores, BBB open-field locomotion test, Louisville Swim Scale (LSS), and CatWalk gait analysis system. Hind limb functional parameters between the two groups using BBB scores and LSS were significantly different (p < 0.05). There were significant differences (p < 0.05) between the SCI group and the sham group for the hind limb functional parameters using the CatWalk gait analysis. We developed an inexpensive custom-made SCI device that yields a precise adjustment of the height and displacement of the impact relative to the spinal cord surface.

Syringic acid protects against thioacetamide-induced hepatic encephalopathy: Behavioral, biochemical, and molecular evidence

The objective of this study was to elucidate the effects of syringic acid on thioacetamide-induced hepatic encephalopathy which is a complex serious syndrome with neuropsychiatric abnormalities related to acute liver dysfunctions like cirrhosis. Rats were treated with syringic acid (50 and 100 mg/kg, p.o.) for 14 days in treatment groups. Hepatic encephalopathy was induced by three doses of (200 mg/kg i.p.) thioacetamide injection. Syringic acid effectively alleviated thioacetamide-induced hepatic injury via reduction in ammonia, AST, ALT, ALP, LDH and decrease in oxidative stress (decreased MDA, ROS and increased SOD and GSH). Syringic acid also attenuated inflammatory injury by suppressing TNF-α, IL-1β, and NF-κB and increasing IL-10. The caspase-3 expression was also down-regulated in both liver and brain tissues. Immunohistochemical results confirmed the recovery with syringic acid by downregulation of iNOS, 8-OHdG and GFAP expression. Syringic acid decreased the deteriorating effects of thioacetamide as seen by reduced ammonia concentration and also preserved astrocyte and hepatocyte structure. The behavioral test results from elevated plus maze test, similar to the open-field locomotor test results, confirmed that syringic acid can reverse behavioral impairments. In conclusion, syringic acid exerted hepatoprotective and neuroprotective effects against hepatic encephalopathy by mitigating hepatotoxicity biomarkers, exerting antioxidant, anti-inflammatory effects in addition to suppressing hyperammonemia.

Bisphenol A exposure during the embryonic period: Insights into dopamine relationship and behavioral disorders in Drosophila melanogaster

Environmental factors are involved in the pathogenesis of neurodevelopmental disorders in addition to genetic factors. In this sense, we demonstrated here that the embryonic exposure of Drosophila melanogaster to Bisphenol A (BPA) 1 mM resulted in changes in development, behavior, and biochemical markers punctuated below. BPA did not alter the oviposition and viability of the eggs, however, it was evidenced a decrease in the rate of pupal eclosion and life span of the hatched flies of the generation filial 1 (F1). F1 flies also developed behavioral changes such as incompatibility in the social interaction between them, and hyperactivity demonstrated by increased locomotion in open field tests, increased grooming, and aggression episodes. Furthermore, decreases in dopamine levels and tyrosine hydroxylase activity have also been observed in flies' heads, possibly related to oxidative damage. Through analyzes of oxidative stress biomarkers, carried out on samples of flies’ heads, we observed an increase in malondialdehyde and reactive species, decrease in the activity of the superoxide dismutase and catalase, which possibly culminated in the reduction of cell viability. Thus, it is important to emphasize that BPA developed atypical behaviors in Drosophila melanogaster, reinforce the importance of the environmental factor in the development of neurobehavioral diseases.

IDO-1 inhibition protects against neuroinflammation, oxidative stress and mitochondrial dysfunction in 6-OHDA induced murine model of Parkinson’s disease

Parkinson’s disease (PD), a common neurodegenerative motor disorder characterized by striatal dopaminergic neuronal loss and localized neuroinflammation in the midbrain region. Activation of microglia is associated with various inflammatory mediators and Kynurenine pathway (KP) being one of the major regulator of immune response, is involved in the neuroinflammatory and neurotoxic cascade in PD. In the current study, 1-Methyltryptophan (1-MT), an Indolamine-2,3-dioxygenase-1 (IDO-1) inhibitor was tested at different doses (2.5 mg/kg, 5 mg/kg and 10 mg/kg) for its effect on behavioral parameters, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, neurotransmitter levels, biochemical and behavioral alterations in unilateral 6-OHDA (3 μg/μL) murine model of PD. The results showed improved locomotion in open field test and motor coordination in rota-rod, reduced oxidative stress, neuroinflammatory markers (TNF-α, IFN-γ, IL-6), mitochondrial dysfunction and neuronal apoptosis (caspase-3). Also, restoration of neurotransmitter levels (dopamine and homovanillic acid) in the striatum and increased striatal BDNF levels were observed. Overall findings suggest that 1-MT could be a potential candidate for further studies to explore its possibility as an alternative in the pharmacotherapy of PD.

Utility of somatosensory and motor-evoked potentials in reflecting gross and fine motor functions after unilateral cervical spinal cord contusion injury.

Fine motor skills are thought to rely on the integrity of ascending sensory pathways in the spinal dorsal column as well as descending motor pathways that have a neocortical origin. However, the neurophysiological processes underlying communication between the somatosensory and motor pathways that regulate fine motor skills during spontaneous recovery after spinal cord contusion injury remain unclear. Here, we established a rat model of cervical hemicontusive injury using C5 laminectomy followed by contusional displacement of 1.2 mm (mild injury) or 2.0 mm (severe injury) to the C5 spinal cord. Electrophysiological recordings were performed on the brachial muscles up to 12 weeks after injury to investigate the mechanisms by which spinal cord pathways participate in motor function. After spinal cord contusion injury, the amplitudes of somatosensory and motor-evoked potentials were reduced, and the latencies were increased. The forelimb open field locomotion test, grooming test, rearing test and Montoya staircase test revealed improvement in functions. With increasing time after injury, the amplitudes of somatosensory and motor-evoked potentials in rats with mild spinal cord injury increased gradually, and the latencies gradually shortened. In comparison, the recovery times of somatosensory and motor-evoked potential amplitudes and latencies were longer, and the recovery of motor function was delayed in rats with severe spinal cord injury. Correlation analysis revealed that somatosensory-evoked potential and motor-evoked potential parameters were correlated with gross and fine motor function in rats with mild spinal cord contusion injury. In contrast, only somatosensory-evoked potential amplitude was correlated with fine motor skills in rats with severe spinal cord injury. Our results show that changes in both somatosensory and motor-evoked potentials can reflect the changes in gross and fine motor functions after mild spinal cord contusion injury, and that the change in somatosensory-evoked potential amplitude can also reflect the change in fine motor function after severe spinal cord contusion injury. This study was approved by the Animal Ethics Committee of Nanfang Hospital, Southern Medical University, China (approval No. NFYY-2017-67) on June 11, 2017.

Ilex paraguariensis Attenuates Changes in Mortality, Behavioral and Biochemical Parameters Associated to Methyl Malonate or Malonate Exposure in Drosophila melanogaster.

Methylmalonic acidemia is a genetic disease characterized by accumulation of organic acids, such as methylmalonic (MMA) and malonic (MA) acids. Considering that the accumulation of MMA and MA causes several damages due to oxidative stress, antioxidants are thought to play a pivotal role in preventing deleterious effects associated with exposure to such compounds. Ilex paraguariensis (IP) was used here to test the hypothesis that supplementation with the aqueous extract of this plant could exert protective effect against MMA or MA induced mortality, behavioral and/or biochemical changes in Drosophila melanogaster (DM). Initially, a curve time- and dose-response to MMA (1-10mM), MA (1-10mM) and IP (63-500μM) was performed. Thereafter, flies were concomitantly exposed to MA (5mM), MMA (5mM) and/or IP (250μg/mL) during 15days for survival assay, and for 48 hs to MA (1 or 5mM), MMA (1 or 5mM) and/or IP (250μg/mL) for subsequent investigations. Both MMA and MA exposure resulted in higher incidence of mortality, a worse performance in the negative geotaxis assay and increased locomotion in open-field test as compared with control group. Furthermore, a marked increase in non-protein thiol (NPSH) and in thiobarbituric acid reactive substances (TBARS) levels, decrease in superoxide dismutase (SOD), catalase and acetylcholinesterase (AChE) activities, and decrease in MTT and resazurin reduction were noted in MMA or MA treated groups. IP treatment offered significant protection against all alterations associated to MMA or MA exposure. This study confirm the hypothesis that supplementation with IP offers protection against changes associated to MMA or MA exposure in DM, due, at least in part, to its antioxidant effect.

Licorisoflavan A Exerts Antidepressant-Like Effect in Mice: Involvement of BDNF-TrkB Pathway and AMPA Receptors.

Depression is a highly debilitating and life-threatening psychiatric disorder. The classical antidepressants are still not adequate due to undesirable side effects. Therefore, the development of new drugs for depression treatment is an urgent strategic to achieving clinical needs. Licorisoflavan A is a bioactive ingredient isolated from Glycyrrhizae Radix and has been recently reported for neuroprotective effects. In this study, the antidepressant-like effect and neural mechanism of licorisoflavan A were explored. In the mice behavioral despair test, we observed that licorisoflavan A exhibited powerful antidepressant-like effect in forced swimming test (FST), tail suspension test (TST), without affecting locomotor activity in open field test (OFT). Additionally, licorisoflavan A administration significantly restored Chronic mild stress (CMS)-induced changes in sucrose preference test (SPT), FST, and TST, without altering the locomotion in OFT. In chronical-stimulated mice, the licorisoflavan A treatment effectively attenuated the expressions of Brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), the phosphorylations of cAMP response element binding protein (CREB), extracellular signal-regulated kinase (ERK)-1/2, eukaryotic elongation factor 2 (eEF2), mammalian target of rapamycin (mTOR), initiation factor 4E-binding protein 1 (4E-BP-1), and p70 ribosomal protein S6 kinase (p70S6K) in hippocampus of CMS-induced mice. Additionally, licorisoflavan A could reverse the decreases in synaptic proteins post-synaptic density protein 95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) caused by CMS, and its antidepressant-like effect was blocked by the AMPA receptor antagonist NBQX. These findings served as preclinical evidence that licorisoflavan A exerted potent antidepressant-like effects involving BDNF-TrkB pathway and AMPA receptors. Licorisoflavan A might be used as a potential medicine against depression-like disorder.

The behavioral effects of CBD and THC in mouse models of psychosis

Approximately 10% of the patients with long-term temporal-lobe epilepsy develop psychotic symptoms, which are known as the “psychosis of epilepsy” (POE). The relationship between the two disorders remains elusive, although they are believed to share similarities in underlying mechanisms and substrates. Previous studies have reported anti-psychotic properties of cannabidiol (CBD) and pro-psychotic properties of Δ 9-tetrahydrocannabinol (THC) in both animals and human patients. The present study investigated the behavioral effects of CBD (60 and 120 mg/kg), THC (4 mg/kg) and a combination of CBD and THC at a 15:1 ratio (60:4 mg/kg) in two mouse models of psychosis – GluN1KD and DATKO mice. The open field locomotion test (OFT) and the pre-pulse inhibition test (PPI) were used. In the OFT, CBD had no significant effect in either mouse model, whereas THC significantly decreased locomotion in both models, (accompanied by an observed impairment in ambulation). In combination, CBD increased THC’s effects in GluN1KD mice and decreased THC’s effects in DATKO mice. In the PPI test, 120 mg/kg of CBD significantly improved PPI in GluN1KD mice. Testing in DATKO mice is still in progress. The behavioral impairments seen in the two mouse models are consistent with other animal models of psychosis. The effects of CBD and THC, however, do not match the prior literature. The cannabinoids used in this work were donated by MedReleaf (Markham, ON). This study was supported in part by EpLink – The Epilepsy Research Program of the Ontario Brain Institute.

Antinociceptive and anti-inflammatory activities of Philodendron bipinnatifidum Schott ex Endl (Araceae)

Ethnopharmacological relevancePopular medicine use stems of Philodendron bipinnatifidum (Araceae) in inflammation cases, such as in erysipelas, as well as orchitis and rheumatism treatment. The present study, conducted for the first time in literature, investigate the antinociceptive and anti-inflammatory activities of P. bipinnatifidum stems ethyl acetate extract (EPB). Materials and methodsGC/MS and HPLC analysis were performed for EPB extract. We used EPB at 250, 375 and 500 mg/kg (oral route, p.o.) in male Swiss mice. The antinociceptive activity of the plant extract assessed by acetic acid induced writhing and formalin tests. To investigate the possible participation of opioid system in EPB-mediated effects, we previously administered naloxone to the mice. Anti-inflammatory activity was evaluated using carrageenan-induced paw oedema. The open-field test aimed to investigate the possible EPB effects on the locomotor and exploratory activities. To assess the protective role of EPB on carrageenan-induced oxidative stress, the levels of NPSH, TBARS, as well as SOD and CAT activities were evaluated in blood and paw tissue. The acute toxicity of the EPB was investigated using OECD 423 guideline. ResultsThe EPB chemical analysis by GC/MS and HPLC revealed the presence of flavonoids (luteolin and quercetin) and phytosterols (β-sitosterol and stigmasterol). The oral treatment with the EPB inhibited mice abdominal writhings (P < 0.01) at 375 and 500 mg/kg, and reduced the formalin effect at the first-phase (500 mg/kg, P < 0.05) and also at the second-phase (500 mg/kg, P < 0.001) of the test. EPB (375 and 500 mg/kg) did not alter spontaneous locomotion in open field test, however the number of fecal bolus was significantly lower for the EPB group at 500 mg/kg when compared to the vehicle group (P < 0.05). The pretreatment with naloxone caused significant inhibition of antinociceptive activity induced by EPB in the formalin test, revealing the possible involvement of opioid receptors. EPB extract administered at 500 mg/kg (p.o.) prevented carrageenan-induced paw oedema (P < 0.05 and 0.01) until 6 h after carragenan injection. Evaluation of TBARS and NPSH levels, SOD and CAT activities in the blood and paw tissue of animals submitted to the carrageenan assay suggested that the anti-inflammatory effect of EPB may be linked to oxidative stress inhibition. The acute administration of the EPB (2000 mg/kg, p.o.) caused no mortality, demonstrating low toxicity. ConclusionsThe extract of P. bipinnatifidum displays antinociceptive and anti-inflammatory activities, causing no toxicological effects. The pharmacological activity of this vegetal species may be related to the presence of flavonoids and phytosterols. Our results support the ethnomedical use of this vegetal species as analgesic and anti-inflammatory agent.

Effect of Aqueous Extract of Blackberry Nightshade (&lt;i&gt;Solanum nigrum&lt;/i&gt;) Leaf on Carbonated Alcoholic Herbal Beverage (CAHB)-Induced Cerebellar Damage and Behavioural Changes in Adult Wistar Rats

This study was aimed at investigating the effect of aqueous extract of Solanum nigrum leaf on carbonated alcoholic herbal beverage-induced cerebellar damage and behavioural changes. Thirty (30) adult Wistar rats weighing between 150g and 220g were allotted into 5 groups of 6 rats each. Animals in group A (control) were placed on normal diet for 56 days. Group B were further subdivided into B1 and B2. Group B1 received 9.4ml/kg of CAHB for 42days, Group B2 received 9.4ml/kg of CAHB for 42 days and were left to recover for the next 14 days. Group C received 400ml/kg (high dose) of S. nigrum only for 56 days. Group D received 9.4ml/kg of CAHB for 42 days and 200m/kg of S. nigrum for the next 14 days. Group E received 9.4ml/kg of CAHB for 42 days and 400mg/kg of S. nigrum for the next 14 days. The result showed that oral administration of CAHB at a dose of 9.4ml/kg body weight daily for 42 days when given to rats, and when they were left to recover for 14 days significantly induced: cerebellar oedema, degeneration of Purkinje cells, vascular stenosis and ulceration, as revealed by reduction in the activity of locomotive, exploratory and anxiety levels of the rats using open field locomotor test. Groups treated with the extract revealed normal cerebellar microstructure. This study has shown that the aqueous extract of S. nigrum leaf has an ameliorative effect on CAHB induced cerebellar damage and behavioural changes. Keywords : CAHB, Behavioural, Cerebellum, Wistar Rats

The T-type calcium channel antagonist, Z944, alters social behavior in Genetic Absence Epilepsy Rats from Strasbourg

Abnormalities in social behavior are a co-morbid symptom of idiopathic generalized epilepsies such as childhood absence epilepsy. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model is a spontaneously occurring absence epilepsy phenotype closely correlated to that of human absence epilepsies. Similar to the human conditions, GAERS display social abnormalities. Previous studies have only demonstrated social abnormalities in female GAERS, whereas social problems are observed in male and female patients. Seizures in GAERS result in part due to a gain-of-function missense mutation in the Cav3.2 T-type calcium channel gene. This study examined the effects of the pan-T-type calcium channel antagonist, Z944, on social interaction behaviors in male and female GAERS using an open field social interaction test. A second objective of this study was to examine the effects of Z944 on anxiety-like behavior in an open field locomotion test and elevated plus maze. Results showed a decrease in social activity in GAERS relative to non-epileptic control (NEC) rats. Acute, systemic Z944 (5 mg/kg; i.p.) consistently reduced introductory and aggressive behaviors in both GAERS and NECs whereas strain effects were observed for over-and-under crawl behaviors. In the open field locomotion test and elevated plus maze, Z944 increased anxiety-like behaviors in GAERS, whereas, Z944 produced inconsistent effects on anxiety-like behaviors in NECs. The results of this study suggest that the regulation of T-type calcium channel activity may be a useful strategy for the development of new therapeutic approaches for the treatment of social and affective abnormalities observed in absence epilepsy disorders.

An 8-Week, Low Carbohydrate, High Fat, Ketogenic Diet Enhanced Exhaustive Exercise Capacity in Mice Part 2: Effect on Fatigue Recovery, Post-Exercise Biomarkers and Anti-Oxidation Capacity.

A low-carbohydrate, high-fat ketogenic diet (KD) is a nutritional approach ensuring that the body utilizes lipids. In our previous study, we found that an eight-week ketogenic high-fat, low-carbohydrate diet increased the capacity of endurance exercise in mice without aggravated muscle injury, despite the decrease of absolute muscle volume. The potential mechanism is most possibly to be enhanced capacity to mobilize and utilize fat. In the present study, we investigated whether a ketogenic diet influences post-exercise recovery by measuring blood biomarkers, muscle and liver oxidative state as well as fatigue recovery 24 h post exercise by employing an open-field locomotion test. Several biochemistry markers indicating exercise-induced injury after exhaustive exercise were improved by KD, followed by a 24-h rest with free feed access, including lactate. No aggravated hepatic oxidative damage was observed, whereas muscular oxidative stress was increased by KD. Accelerated recovery induced by exhaustive exercise was also observed from blood biomarkers of injury. For fatigue recovery, lactate concentration, a marker often employed as exhaustion index was lowered by KD, whereas an open field test showed that KD application contributed to increased locomotion after exhaustive exercise, followed by a 24-h rest. These results suggest that KD has the potential to be used as a fatigue-preventing and/or recovery-promoting diet approach in endurance athletes.

Necrosulfonamide Attenuates Spinal Cord Injury via Necroptosis Inhibition

Spinal cord injury (SCI) is a serious trauma without efficient treatment currently. Necroptosis can be blocked post injury by special inhibitors. This study is to investigate the effects, mechanism, and potential benefit of necrosulfonamide (NSA) for SCI therapy. Pathologic condition was detected using hematoxylin-eosin staining on injured spinal cord and other major organs. Necroptosis-related factors-RIP1, RIP3, and MLKL-were detected using Western blot. Detections on mitochondrial functions such as adenosine triphosphate generation and activities of superoxide dismutase and caspase-3 were also performed. Finally, ethologic performance was detected using a 21-point open-field locomotion test. Reduced lesions and protected neurons were found in the injured spinal cord after treatment with NSA using hematoxylin-eosin staining for pathologic detection. No obvious toxicity on rat liver, kidney, heart, and spleen was detected. Rather than RIP1 and RIP3, MLKL was significantly inhibited by the NSA using Western blot detection. Adenosine triphosphate generation was obviously decreased post injury but slightly increased after the NSA treatment, especially 24 hours post injury. No significant changes were found on activities of superoxide dismutase and caspase-3 after the treatment of NSA. Ethologic performance was significantly improved using a 21-point, open-field locomotion test. Our research indicates NSA attenuates the spinal cord injury via necroptosis inhibition. It might be a potential and safe chemical benefit for SCI therapy. To our knowledge, this is the first study on the effects of NSA as treatment of traumatic SCI.

Epidermal growth factor regulates apoptosis and oxidative stress in a rat model of spinal cord injury

Spinal cord injury (SCI) leads to vascular damage and disruption of blood-spinal cord barrier which participates in secondary nerve injury. Epidermal growth factor (EGF) is an endogenous protein which regulates cell proliferation, growth and differention. Previous studies reported that EGF exerts neuroprotective effect in spinal cord after SCI. However, the molecular mechanisms underlying EGF-mediated protection in different regions of nervous system have not shown yet. In this study, we aimed to examine possible anti-apoptotic and protective roles of EGF not only in spinal cord but also in brain following SCI.Twenty-eight adult rats were divided into four groups of seven animals each as follows: sham, trauma (SCI), SCI + EGF and SCI + methylprednisolone (MP) groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic protein levels and antioxidant enzyme activities were measured in spinal cord and frontal cortex.In our study, EGF promoted locomotor recovery and motor neuron survival of SCI rats. EGF treatment significantly decreased Bax and increased Bcl-2 protein expressions both in spinal cord and brain when compared to SCI group. Moreover, antioxidant enzyme activities including catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were increased following EGF treatment similar to MP treatment. Our experiment also suggests that alteration of the ratio of Bcl-2 to Bax may result from decreased apoptosis following EGF treatment. As a conclusion, these results show, for the first time, that administration of EGF exerts its protection via regulating apoptotic and oxidative pathways in response to spinal cord injury in different regions of central nervous system.

The comparison of neurobehavioral changes and impaired locations between the mouse model of manganism and Parkinson's disease

Objective: To investigate the effect of manganese chloride (MnCl(2)) or 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) on the neurobehavioral and histopathology in C57BL/6 mice and provide evidence for the diagnosis, treatment and prevention of manganism. Methods: Adult male C57BL/6 mice were treated with MnCl(2) and MPTP respectively by intraperitoneal injection at the doses of 5, 10, 20mg Mn/kg and 30mg MPTP/kg. Controls were injected equivalent normal saline. All animals were administrated 5 times a week for 4 consecutive weeks and sacrificed after behavior tests on the fifth week. Balance ability, anxiety and depression level and cognitive function were tested respectively by vertical pole test, open field locomotion test and Morris swim task. The neuron pathological changes of striatum and substantia nigra were examined through HE-staining pathological section by using optical microscope. Results: Compared with the control group, the high dose of MnCl(2) reduced body weight obviously (P<0.01) . The results of vertical pole test showed that MnCl(2) and MPTP lengthened the pole-climbing time and turnaround time. Open field locomotion test showed that movement distance, stand-up time and central field time were decreased after the exposure of MnCl(2) or MPTP. In the Morris swim task, the escape latency time increased and the target quadrant activity time decreased significantly after the injection of MPTP as well as high-dose MnCl(2), comparing with controls (P<0.05) . Moreover, the escape latency time of high dose MnCl(2) prolonged prominently comparing with MPTP grou (P<0.05) . The results of histopathology showed that acidophilic changes elevated in MnCl(2) and MPTP group, comparing with controls. Furthermore, in striatum the oxyphil cells number increased in MnCl(2) high-dose group comparing with MPTP group (P<0.01) . On the contrary, there were more oxyphil cells in MPTP group comparing with MnCl(2) groups in substantia nigra (P<0.01) . Conclusion: Both manganese and MPTP can induce the impairment of dopaminergic neural system, but the symptons and injured location of manganism are inconsistent with PD models induced by MPTP.

Abstract WMP103: Role of the Soluble TLR4 Decoy Receptor on ICH Outcomes

Background: Of all subdivisions of stroke, intracerebral hemorrhagic stroke (ICH) only accounts for around 10-15% but is characterized by the highest mortality and morbidity. Lately, understanding immunological and inflammatory responses post-hemorrhagic stroke allows for the development of alternative therapeutic intervention. Toll-like receptors (TLR) are a large family of recognition receptors which have a regulatory pathway that is a key factor in determining the neurological outcomes of patients with ICH. In this study, we took a closer look at understanding the role that the overexpressing the soluble Toll-like receptor 4 (sTLR4) has on neuroprotection after ICH. Methods: Intracerebral injections of autologous blood were used to induce the ICH preclinical model on adeno-associated virus serotype 1 (rAAV1)-mediated FcV5 (control) and FcV5-sTLR4 expression in the brains of mice. Functional outcomes of these mice were assessed using several behavioral testing methods such as rotarod, open field locomotor test, and a neurological deficit score (NDS) at the different time-points of 24h, 48h and 72h. To assess changes to the lesion, hematoma and tissue injury, a histological stain, cresyl violet, was performed. Results: The data reveal a 41.9+/-8.2% smaller lesion volume in sTLR4 overexpressed mice. Further analysis with histological and immunochemical stains shows a trend towards a smaller tissue injury and hematoma volume, unchanged heme oxygenase 1 and iron levels, and unchanged microgliosis and astrogliosis levels. Conclusion: These findings reveal that the overexpression of sTLR4 does improve preliminary ICH outcomes. We will also discuss mechanisms behind the relationship between sTLR4 signaling and ICH along with possibilities of future methods of therapeutic interventions.

Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury?

Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining) and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

Neuroinflammatory reactions in sickness behavior induced by bacterial infection: Protective effect of minocycline.

The neurological changes elicited by bacterial infection are called sickness behavior. Minocycline (MIN) is neuroprotective with a remarkable brain tissue penetration. MIN was orally administered at a dose 90mg/kg for 3 days, whereas Escherichia coli was given as a single intraperitoneal injection (0.2mL of 24h growth) on the third day. After 24h of bacterial infection, behavioral tests namely open field and forced swimming were carried out, then animals were decapitated. Rats infected with E. coli displayed reduced struggling time in forced swimming test, as well as, exploration and locomotion in open field test with reduction in neurotransmitters (norepinephrine, dopamine, and serotonin) versus elevation in the inflammatory (tumor necrosis factor-alpha, interferon-gamma) and oxidative stress (thiobarbituric acid reactive substance, reduced glutathione) biomarkers. Inflammatory infiltrates of nuclear cells were observed in brains of infected rats. MIN administration prevented the deleterious effects of E. coli infection, thus protects against sickness behavior possibly via defending from neuroinflammation.

Oxytocin reduces alcohol consumption in prairie voles

Alcohol use disorder (AUD) negatively affects millions of people every year in the United States, and effective treatments for AUD are still needed. The neuropeptide oxytocin has shown promise for reducing alcohol drinking in mice and rats. Because oxytocin also plays a key role in complex prosocial behaviors like bonding and attachment, we tested the effect of oxytocin on alcohol drinking in prairie voles, a species that both consumes high amounts of alcohol and forms oxytocin dependent social bonds in a manner similar to humans. Oxytocin treatment (1.0, 3.0, and 10.0mg/kg, i.p.) reduced alcohol consumption in male and female prairie voles in animals that had access to 15% ethanol vs water every other day for 12 alcohol drinking sessions. In animals with continuous access to 15% alcohol and water, oxytocin (3.0mg/kg) reduced alcohol consumption only in the first hour of access after treatment, with no significant effects on consumption over the 24-hr period. In an open field locomotor test, oxytocin (1.0, 3.0, and 10.0mg/kg, i.p.) did not affect overall locomotor activity; however, ethanol (2g/kg, i.p.) increased locomotor activity in males and females, and produced anxiolytic effects (increased time in the center of an open field) in females only. Because prairie voles have been shown to match the alcohol consumption of their cage mate, we evaluated the relationship between cage mates' alcohol drinking. There was an overall pattern of social facilitation (consumption by one cage mate predicted consumption by the other cage mate); however, we found significant individual differences across cages in which many cages did not show significant matching, and, in some cases one cage mate's consumption negatively predicted the other cage mate's consumption. Overall, our data provide support for the potential of oxytocin as a treatment to reduce alcohol consumption.