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Nonenhancing motor eloquent gliomas: navigated transcranial magnetic stimulation oncobiological signature.

Preoperative grading of nonenhancing motor eloquent gliomas is hampered by a lack of specific imaging surrogates. Tumor grading is crucial for the informed consent discussion before tumor resection. In this paper, the authors hypothesized that navigated transcranial magnetic stimulation (nTMS)-derived metrics could provide significant information to distinguish between high- and low-grade motor eloquent gliomas that present as nonenhancing tumors and therefore contribute to improving patient counseling, timing of treatment, preoperative planning, and intraoperative strategies. The authors conducted a retrospective single-center cohort study of patients admitted for tumor surgery between January 2018 and April 2022 with a nonenhancing motor eloquent glioma and preoperative bilateral nTMS mapping. nTMS data including resting motor threshold (RMT), interhemispheric RMT ratio (iRMTr), Cortical Excitability Score (CES), area and volume of cortical activation, and motor evoked potential (MEP) characteristics were obtained and integrated with demographic and clinical data. Thirty patients met the inclusion criteria, and 10 healthy participants were recruited for comparison. Seizures were the most common presenting symptom (25 patients) and WHO grade 3 the most common tumor grade (21 patients). The area and volume of functional cortical activation of both the abductor pollicis brevis and first dorsal interosseous muscles were decreased in healthy participants compared with patients with WHO grade 3 glioma (p < 0.05). An abnormal iRMTr for the lower limbs (16.7% [1/6] WHO grade 2, 76.2% [16/21] WHO grade 3, 100% [3/3] WHO grade 4; p = 0.015) and a higher CES (maximal abnormal CES: 0% [0/6] WHO grade 2, 38% [8/21] WHO grade 3, 66.7% [2/3] WHO grade 4; p = 0.010) were associated with the prediction of high-grade lesions. A total of 7280 MEPs were analyzed. A significant increase in the amplitude and a significant decrease in latency in the MEPs for the first dorsal interosseous and abductor digiti minimi muscles (p < 0.0001) were identified in healthy participants compared with WHO grade 3 glioma patients. Nonenhancing motor eloquent gliomas have a different impact on both anatomical and functional reorganization of motor areas according to their WHO grading.

Memory impairment effect of Cannabidiol Oil and Prednisolone Treatment: Alteration of Neuro-oxidant markers and Acetylcholinesterase Activity in the Hippocampus of Cadmium-Induced Toxicity in Male Wistar Rats

Background: There have been conflicting reports on the effect of Cannabis products on learning and memory. Hence this study investigated CBD oil's and prednisolone treatment's cognitive impact on cadmium-induced toxicity in male Wistar rats.&#x0D; Methods: Forty rats weighing between 150g to 200g were assigned into 8 groups (1-8) of five animals each. Group A control, Group B-H received 1mg/kg body weight prednisolone; 1.5mg/kg Cadmium; 1mg/kg pred+0.2mg/kg CBD-oil; 0.2mg/kg CBDoil+2mg/kg cadmium; 3mg/kg pred+2mg/kg cadmium; 0.1mg/kg CBD-oil and 0.2mg/kg CBD-oil respectively. The administration was done using gavage for 14 days. A T-maze test apparatus was used to determine the latency of object recognition before and after administration.&#x0D; Results: There was a significant decrease in latency of object recognition in prednisolone, cadmium, and 0.2mg/kg CBD-oil treated groups than control after administration. Calcium ion significantly (P&lt;0.05) increased in the cadmium+ 0.1mg/kg CBD-oil treated group and decreased in the pred+CBD-oil group compared to the control. Acetylcholinesterase significantly (P&lt;0.05) increased in prednisolone, pred+cadmium, and 0.2mg/kg CBD-oil treated groups and decreased in cadmium, pred.+CBD-oil, cadmium+CBD-oil, and 0.1mg/kg CBD-oil treated groups compared to control. Catalase significantly increased in pred+cadmium, 0.1mg/kg CBD-oil, and 0.2mg/kg CBD-oil treated groups compared to control. SOD significantly decreased in the treatment groups than the control. Malondialdehyde significantly increased in cadmium, pred+CBD-oil, cadmium+CBD-oil, 0.1mg/kg CBD-oil, and 0.2mg/kg CBD-oil than control. Glutathione peroxidase significantly decreased in treated groups compared to control. Reduced glutathione significantly decreased across treated groups than the control. Histology of the hippocampus revealed visible pathologic changes in pred+cadmium, 0.1mg/kg CBD-oil, and 0.2mg/kg CBD-oil treated groups with cellular vacuolization, Perivascular leucocyte infiltration, and pycnotic nuclei, indicating slight inflammation and detrimental effects of the treatment in the histoarchitecture of the hippocampus.&#x0D; Conclusions: CBD oil, prednisolone, and cadmium administration at different doses induced biochemical alterations, and exacerbated cognitive and neurobehavioral decline by enhancing oxidative stress, acetylcholinesterase activity, and alteration in the cytoarchitecture of the hippocampus

Brainstem impairment in obstructive sleep apnoea and the effect of CPAP treatment: an electrophysiological blink reflex study

PurposeThis study aimed to evaluate the functionality of the brainstem structures through the blink reflex (BR) test in patients with obstructive sleep apnoea (OSA) and to assess the effects of continuous positive airway pressure (CPAP) treatment on BR responses.MethodsPatients with moderate-severe OSA and controls underwent BR testing. Patients with OSA who were adherent to CPAP therapy repeated BR testing at 6 months follow-up. CPAP adherence was defined as CPAP use for ≥ 4 hour per night on > 5 nights per week with residual apnoea-hypopnea index less than 5 events per hour.ResultsA total of 22 patients with OSA (86% male, mean age 57.8 ± 10.6 years) and 20 controls (60% male, mean age 55.3 ± 9.3 years) were included. Patients with OSA showed longer right and left R1 latency, as well as delayed right ipsilateral and contralateral R2 latencies compared to controls. Patients with OSA who were compliant with CPAP treatment (n = 16; 88% men, mean age 58.8 ± 9.7 years) showed a significant decrease in latency of the right ipsilateral and contralateral R2 responses at 6 months.ConclusionThis study showed an abnormal pattern of BR responses in patients with OSA, consistent with a significant impairment of brainstem functionality in OSA. CPAP treatment partially improved the BR responses, suggesting the importance of treating OSA.

Trends in referral patterns to presurgical evaluation at a European reference center

PurposeTo determine if growing evidence for epilepsy surgery as an early treatment option is reflected in the decrease of latencies between epilepsy onset and referral for presurgical evaluation MethodsRetrospective analysis of latencies in 1646 patients (children and adults) from the time of epilepsy diagnosis to first presurgical workup in the period from 1999 to 2019 based on electronic patient charts at a tertiary epilepsy center. Time spans 1999–2009 and 2010–2019, prior to and following the ILAE definition of pharmacoresistance, and the role of etiological factors were assessed. ResultsOver the whole period, the mean latency between diagnosis and a presurgical workup was 15.3 y. There was a significant reduction in the latencies between the periods 1999–2009 (16.9 y) and 2010–2019 (13.4 y), (p < 0.0001). In a linear regression analysis, the latency decreased by 2.6 months/year from 17.4 in 1999 to 13.1 y in 2019 (p < 0.001). Subgroup analyses showed significant decreases in latency to presurgical evaluation in patients with hippocampal sclerosis from 24.4 to 19.5 y, in malformations of cortical development from 16.4 to 13.2 y, and in nonlesional patients from 18.1 to 12.8 y, in contrast to patients with MR evidence for brain tumors with similar latencies across time (10.5 vs. 9.5 y, n.s.). ConclusionThe reduction of the time span to a first presurgical evaluation was highly significant over time, yet moderate in its degree. Overall, the aim of early diagnostic evaluation for epilepsy surgery options after established pharmacoresistance was only achieved for a minority of patients.

Glimepiride Prevents 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Induced Dopamine Neurons Degeneration Through Attenuation of Glia Activation and Oxidative Stress in Mice.

It is well established that there is a link between type 2 diabetes mellitus and Parkinson's disease (PD) evidenced in faster progression and more severe phenotype in patients living with diabetes suggestive of shared cellular pathways; hence, antidiabetic drugs could be a possible treatment options for disease modification. This study evaluated the effect of glimepiride (GMP), a third generation sulphonylurea, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice. Sixty mice were divided randomly into six individual groups of 10 mice each and dose orally as follows: group 1: vehicle (10ml/kg, p.o.); group 2: MPTP (20mg/kg, i.p. × 4 at 2-h interval); groups 3-5: GMP (1, 2, or 4mg/kg, p.o.) + MPTP (20mg/kg, i.p. × 4 at 2-h interval); and group 6: GMP (4mg/kg, p.o.). Effect of glimepiride on motor activities were appraised with the use of open-field test and rotarod performance while non-motor activity was evaluated using force swim test (FST; depression) and Y-maze test (working memory). MPTP induced significant decrease in latency to fall on rotarod, distance covered/rearing in open field, mean speed and climbing in FST, and percentage alternation behavior in Y-maze suggestive of motor and non-motor dysfunction. However, MPTP-induced motor and non-motor dysfunction were ameliorated with glimepiride post-treatment. In addition, MPTP-induced increase in oxidative stress parameters and cholinergic neurotransmission was attenuated by glimepiride. In addition, MPTP-induced nigral dopamine neuron loss (decrease in tyrosine hydroxylase-positive neuron (TH)) and neuroinflammation (activation of glial fibrillary acid protein (GFAP) and ionized calcium binding adaptor molecule 1 (iba-1)) were ameliorated by GMP administration. This study showed that glimepiride ameliorates MPTP-induced PD motor and non-motor deficits through enhancement of antioxidant defense signaling and attenuation of neuroinflammatory markers. Thus, this could be useful as a disease-modifying therapy in the management of PD.

The impact of multisensory integration and perceptual load in virtual reality settings on performance, workload and presence

Real-world experience is typically multimodal. Evidence indicates that the facilitation in the detection of multisensory stimuli is modulated by the perceptual load, the amount of information involved in the processing of the stimuli. Here, we used a realistic virtual reality environment while concomitantly acquiring Electroencephalography (EEG) and Galvanic Skin Response (GSR) to investigate how multisensory signals impact target detection in two conditions, high and low perceptual load. Different multimodal stimuli (auditory and vibrotactile) were presented, alone or in combination with the visual target. Results showed that only in the high load condition, multisensory stimuli significantly improve performance, compared to visual stimulation alone. Multisensory stimulation also decreases the EEG-based workload. Instead, the perceived workload, according to the “NASA Task Load Index” questionnaire, was reduced only by the trimodal condition (i.e., visual, auditory, tactile). This trimodal stimulation was more effective in enhancing the sense of presence, that is the feeling of being in the virtual environment, compared to the bimodal or unimodal stimulation. Also, we show that in the high load task, the GSR components are higher compared to the low load condition. Finally, the multimodal stimulation (Visual-Audio-Tactile—VAT and Visual-Audio—VA) induced a significant decrease in latency, and a significant increase in the amplitude of the P300 potentials with respect to the unimodal (visual) and visual and tactile bimodal stimulation, suggesting a faster and more effective processing and detection of stimuli if auditory stimulation is included. Overall, these findings provide insights into the relationship between multisensory integration and human behavior and cognition.

Effect of acute bout of moderate exercise on P300 component of event-related potential in young women during different phases of menstrual cycle: A pilot study

Objectives: Ovarian hormones not only regulate reproductive functions but also are implicated in emotional and cognitive processing. But, menstrual cycle studies do not provide convincing evidences. However, evidence supports a link between estrogen depletion and risk for Alzheimer’s disease. Physical exercise has shown to improve a person’s attentiveness and cognitive skills. Since both exercise and ovarian hormones may affect cognition, the present study intends to determine the effect of acute bout of moderate exercise on cognitive processing in young women in early proliferative phase and mid-luteal phase. Materials and Methods: It was a cross-sectional, observational study conducted on young, normally menstruating women of 18-35 years (n = 20). Each participant attended two laboratory sessions, early follicular phase (initial 3 days post-menstruation) and mid luteal phase (days 21-24). The participants filled up Godin Leisure-Time Exercise Questionnaire (GLTEQ) and their basal central, brachial blood pressures and P300 Event Related Potential (ERP) were recorded. Then, the subjects performed step test till they achieved 60-80% of their maximum heart rate. Afterwards, their central and brachial blood pressure and heart rate were recorded. The participants then filled up Borg perceived exertion scale questionnaire. Post exercise P300 ERP was recorded after 15 min of exercise. Results: Significant changes in all cardiovascular parameters in post-exercise session were observed in both phases of menstrual cycle. The amplitude and latencies of P300 ERP showed no significant difference at resting state (pre-exercise) during both phases. P300 ERP latency showed significant decrease in post-exercise session when recorded at Cz (P = 0.024, P = 0.05) and Pz position (P = 0.03, P = 0.003) in both phases except in Fz position. But there was no significant change in amplitude. MANCOVA analysis revealed that only amplitude of P300 ERP (P = 0.023) in post-exercise session during mid-luteal phase was affected by basal activity level significantly. Conclusion: The present study documented that an acute bout of moderate exercise caused significant decrease in latency of P300 ERP in the participants during both phases of menstrual cycle. Therefore, it can be stated that even acute bout of moderate exercise significantly enhances attention allocation, working memory in the participants; thereby it enhances cognitive functioning of the individual.

Increasing Access to Autism Spectrum Disorder Diagnostic Consultation in Rural and Underserved Communities: Streamlined Evaluation Within Primary Care.

Preliminary feasibility and clinical utility research has demonstrated that implementation of a streamlined diagnostic model embedded within primary care (PC) clinics promotes early identification of young children with autism spectrum disorder (ASD). Use of this model results in dramatically reduced waits for diagnostic consultation, high levels of family/provider satisfaction, and reductions in referrals to overtaxed tertiary diagnostic centers. The current study extends this work by providing data before/after implementation of a streamlined model across a diverse range of PC clinics that provide health care to rural and underserved communities. The streamlined assessment involved record/history review, diagnostic interview, standard rating scales, and an interactive screening tool. Eighty children between the ages of 19 and 47 months were seen across 5 different clinics. Data were collected through chart review. Implementation of streamlined model resulted in a significant decrease in latency to diagnostic conclusion from a mean of 144.7 to 49.9 days. Children were likely to experience a greater reduction in wait times if they were a PC patient versus a non-PC patient. Results show significant reduction in wait times for ASD diagnostic decisions across both PC and non-PC patients. By reducing waits and identifying concerns more efficiently, we may increase the ability of families to access early intervention and support services.

Central nervous system depressant activity of Jatamansi (Nardostachys jatamansi DC.) rhizome.

Background:Sleep disorders have a comparatively high prevalence worldwide and create a burden on the health system. Pharmacological agents used for insomnia are associated with considerable side effects. Therefore, searching for safe and effective agents from plant-based natural sources is a worthy effort. Jatamansi (Nardostachys jatamansi DC.) rhizome has been recommended for insomnia and mental conditions in the Indian system of medicine.Aim:This study aimed to determine central nervous system (CNS) depressant activity of Jatamansi (N. jatamansi) rhizome on experimental animals.Materials and methods:Gross behavior study and open field test (locomotor activity) were performed by using Charle’s foster albino rats whereas rota-rod test and pentobarbital-induced sleep test in Swiss albino mice. Animals were divided into 3 groups (per model) having six animals in each group. The control group was treated with water, the standard group with diazepam and the test drug with powder of N. Jatamansi rhizome. Results were calculated by one-way ANOVA and post hoc test with P < 0.05 as significant.Results:Data suggested that Jatamansi did not produce a significant effect on the behavior of animals. It reduced the horizontal activity significantly (P < 0.001) in the open field apparatus. The test drug did not show a significant decrease in latency of fall-off time in rota-rod performance in mice. Still, it exerted a significant effect by a reduction in latency of onset of sleep (P < 0.01) and also extended the total duration of sleep (P < 0.05) in albino mice in comparison to the control group.Conclusion:This study shows that Jatamansi rhizome powder possesses CNS depressant activity without affecting gross behavior and muscle coordination in rats.

Haloperidol-induced parkinsonism is attenuated by varenicline in mice.

Background Parkinson's disease (PD) is a neurodegenerative disorder of the central nervous system (CNS). However, there is no known drug to stop/slow down this neurodegeneration. Varenicline is an anti-smoking drug and has the potential to prevent neurodegeneration. Thus, the present study was designed to evaluate the effect of varenicline in animal models of PD. Methods Levodopa and haloperidol were administered in doses of 30 and 1 mg/kg, intraperitoneally (i.p.), respectively. Group 1 was administered haloperidol; groups 2, 3 and 4 were administered haloperidol along with varenicline in doses of 0.5, 1.5 and 2.5 mg/kg, i.p., respectively and group 5 was administered levodopa along with haloperidol. Varenicline was administered daily, 30 min prior to the administration of haloperidol. Varenicline was administered for the first 8 days, and then from the 9th day until the 15th day. Behavioral assessment (rotarod and catalepsy tests) was performed on days 9 and 15. Assessment of striatal dopamine levels and histopathology were also performed. Results In the haloperidol-treated groups, significant decrease in latency to fall off (on rotarod) and increase in catalepsy duration (in catalepsy test) were observed as compared to the control group. In the levodopa-treated group, significant increase in latency to fall off the rotarod and significant decrease in catalepsy duration were observed as compared to the haloperidol-treated groups. Further, on day 9, varenicline (2.5 mg/kg) significantly increased the latency to fall off the rotarod, while varenicline (0.5 and 1.5 mg/kg) did not cause any significant change in latency to fall off the rotarod as compared to the haloperidol-treated group. On day 15, significant increase in latency to fall off the rotarod was observed in varenicline (at all doses) as compared to the haloperidol-treated group. In the catalepsy test, the varenicline-treated (at all doses) groups showed significant decrease in duration of catalepsy on day 9 and day 15 as compared to the haloperidol-treated group. Significant decrease in striatal dopamine levels was observed among the haloperidol-treated groups as compared to the control group. Further, varenicline-treated (at all doses) and levodopa-treated groups showed significant increase in striatal dopamine levels when compared with the haloperidol-treated group. In histology, varenicline (0.5 mg/kg) showed moderate decrease in neurons, while varenicline (1.5 and 2.5 mg/kg) showed mild decrease in neurons. However, the levodopa-treated group did not show any significant decrease in neurons. Thus, varenicline has shown promising results and has provided novel strategy for the treatment of PD.

CNS Activity of Myristica fragrans Houtt. - An Experimental Study

Objective: To evaluatethe role of Myristica fragrans Houtt. for its analgesic, sedative and anxiogenic activity.Method: Charles Foster rats were administered orally the ethanolic extract (EEMF) and fractions of extract in ethyl acetate (EAMF), chloroform (CMF), and n-hexane (HMF). They were screened for sedative activity using Pentobarbitone sleep potentiation test, analgesic activity using Eddy’s hot plate and Tail flick test; and anxiogenic or anxiolytic activity using Open field test.Result: In pentobarbitone induced sleep potentiation test, the ethanolic extract (EEMF) and ethyl acetate fraction (EAMF) showed significant decrease in latency of sleep and highly significant increase in duration of sleep. In Open field test, EEMF, EAMF and HMF showed highly significant decrease in locomotion parameters as shown by decrease in rearing, preening and ambulation. In Eddy’s hot plate test and Tail flick test, highly significant increase in reaction time was seen in EEMF, EAMF, HMF groups.Conclusion: The observed results suggest that Myristica fragrans has analgesic, anxiogenic and sedative activity.Bangladesh Journal of Medical Science Vol.17(1) 2018 p.98-106

Systematic review and meta-analysis of the efficacy of different exercise programs in pilocarpine induced status epilepticus models.

To conduct a systematic review and meta-analysis of studies testing exercise in animal models of pilocarpine induced status epilepticus (SE) and to compare the efficacy of different training strategies used in those studies. We searched 2 online databases (Pubmed and Web of Science) for studies analyzing the efficacy of different trainings in pilocarpine-induced SE models. Training was categorized into forced physical training (PT), voluntary PT and resistance PT. Two reviewers independently extracted data on study quality, behavioral seizures, and histological, chemical and cognitive outcomes. Data were pooled by means of a meta-analysis. Among 17 selected studies; 174 animals from 8 studies with 10 comparison groups showed that exercise intervention after induction of SE significantly decreased spontaneous recurrent seizures with [mean difference (MD)=-1.80, 95% confidence interval (CI): -3.22, -0.37, p=0.02] and 60 animals showed statistically significant decrease in latency in Morris water maze (standardized mean difference (SMD)=-2.57, 95% CI: -4.06, -1.08, p=0.0007). Although not statistically significant, still a remarkable increase in number of CA1 neurons and hippocampal BDNF level (MD=2.27, [95% CI: -1.20, 5.73], p=0.19, SMD=1.07, [95% CI: -0.36, 2.51], p=0.14 respectively) and a decrease in mossy fibers sprouting (SMD=-1.03, [95% CI: -3.06, 1.00], p=0.32) were observed. PT interventions in 72 animals before induction of SE showed favorable increase in latency to develop SE (MD=8.34, [95% CI: -3.10, 19.78], p=0.15) but no remarkable improvements in latency for the first motor sign and motor signs intensity. PT after SE reduces the recurrent seizures and improves the morphological, biochemical and cognitive profiles of pilocarpine epileptic models. Resistance PT was identified as particularly effective in reducing behavioral seizures. The efficacy of training was also dependent upon duration.

3D network-on-chip design for embedded ubiquitous computing systems

A novel 3D NoC topology for embedded ubiquitous computing is proposed.A minimal routing algorithm with path diversity in the 3D NoC Topology is used.A power efficient architecture design for NoC-based embedded ubiquitous computing is introduced. Ubiquitous High-Performance Computing applications, such as cyber-physical systems, sensor networks and virtual reality require the support of terascale embedded systems that can deliver higher performance than current systems. Multi-cores, many-cores and heterogeneous processors are becoming the typical design choices to satisfy these requirements. Inter core communication has been one of the major challenges as it affects the bandwidth and power consumption of the multi-cores processors. Network-on-Chips (NoCs) present a fast and scalable interconnection solution to fulfill the requirements of Ubiquitous High-Performance Computing applications. This paper proposes a novel 3D Network-on-Chip called Octagon for Ubiquitous Computing (OUC) that is designed for Embedded Ubiquitous Computing Systems. OUC provides low network diameter and path diversity. Simulation results show that the proposed topology achieves a significant decrease in latency and an average 21.54% and 12.89% improvement in average throughput under hotspot and uniform traffic pattern respectively.

Intra-amygdala microinjections of chlorpheniramine impair memory formation or memory retrieval in anxiety- and fear-mediated models.

H1 receptor histaminergic antagonist, chlorpheniramine (CPA) participates in cognitive performance in various animal models. However, little is known regarding the effects of CPA microinjection into the amygdala on emotional behavior. The purpose of this study was to investigate whether CPA microinjection into the amygdala has the same effect on two models, one anxiety- and the other fear-mediated, in various memory stages using the elevated plus maze (EPM) and the inhibitory avoidance task (IAT) tests. Two experiments were performed with seventy-two adult male Swiss mice. Behavioral testing was performed on two consecutive days, and in both experiments, before each trial, the animals received bilateral microinjections of saline (SAL) or CPA (0.16 nmol). The animals were re-exposed to the EPM or IAT 24h after the first trial. Four experimental groups were tested: SAL-SAL, SAL-CPA, CPA-SAL and CPA-CPA. In experiment 1, a decreased open arm exploration (% open arm entries, %OAE and% open arms time, %OAT) for SAL-SAL and SAL-CPA was showed, while these measures did not decrease for the CPA-SAL and CPA-CPA groups in Trial 2. In experiment 2, an increase of retention latency in relation to training 2 for the groups SAL-SAL and CPA-SAL and a significant decrease in latency for the group SAL-CPA was revealed. These results indicate that chlorpheniramine microinjection into the amygdala impairs emotional memory acquisition and/or consolidation in the EPM and retrieval of IAT.

NSAIDs attenuate hyperalgesia induced by TRP channel activation.

Transient receptor potential (TRP) cation channels have been extensively investigated as targets for analgesic drug discovery. Because some non-steroidal anti-inflammatory drugs (NSAIDs) are structural analogs of prostaglandins (mediators of inflammation) and NSAIDs attenuate heat nociception and mechanical allodynia in models of inflammatory and neuropathic pain, we examined three widely used NSAIDs (diclofenac, ketorolac, and xefocam) on the activation of TRPA1 and TRPV1 channels using thermal paw withdrawal (Hargreaves) test and mechanical paw withdrawal (von Frey) test in male rats. Thermal withdrawal latencies and mechanical thresholds for both hind paws were obtained with 5, 15, 30, 45, 60, and 120 min intraplantar post-injection of TRPA1 agonizts, allyl isothiocyanate (AITC) (a natural compound of mustard oil) and cinnamaldehyde (CA), and TRPV1 agonist capsaicin or vehicle. Twenty minutes prior to the start of the experiment with TRP agonizts, diclofenac, ketorolac or xefocam were pre-injected in the same hindpaw and animals were examined by these two tests. After pretreatment of all three NSAIDs in the ipsilateral (injected) hindpaw that produced strong antinociceptive effects, AITC, CA, and capsaicin caused significant decreases in latency of the thermal withdrawal reflex compared with vehicle or the contralateral hindpaw. The same findings were observed for the paw withdrawal threshold. In approximately 30 min the effects of CA, AITC, and capsaicin returned to baseline. The data are different from our previous evidence, where TRPA1 agonizts AITC and CA and TRPV1 agonist capsaicin produced hyperalgesia for nearly 2 h and resulted in facilitation of these withdrawal reflexes (Tsagareli et al., 2010, 2013). Thus, our data showing that NSAIDs suppress thermal and mechanical hyperalgesia following TRP activation could presumably due to inactivation or desensitization of TRPA1 and TRPV1 channels by NSAIDs.

Dermatomal Somatosensory Evoked Potentials: An Indicator of Improvement of Breast Sensibility after Reduction Mammaplasty

Introduction: Many women think about reduction mammaplasty for different reasons. The effect of surgery on the beast sensibility is one of the greatest concerns after reconstructive reductive breast surgery through its affect on patient’s social life and psychological health. The dermatomal somatosensory evoked potential (D-SEP) is a new method to quantitatively evaluate breast sensibility. Patients and Methods: Twenty-five women enrolled in this study presenting with breast enlargement, underwent mammary reduction by using the inferior pyramidal breast reduction technique using the same operative technique described by Robbins with some modifications. All D-SEP amplitudes and latencies were calculated preoperatively and then were reassessed six and twelve months post-surgery in each breast. Result: The results revealed that there is a significant difference in the D-SEP latency pre- and post-operatively. The statistically significant decrease in latency and the breast size demonstrated indicates that the sensibility improved after breast reduction surgery both at six and twelve months. There is also a significant increase in the D-SEP amplitude pre- and post-operatively. The negative and statistically significant increase in amplitude with the decrease in breast size demonstrated indicates that the sensibility improved after breast reduction surgery both at six and twelve months. Conclusion: This study concluded that breast sensibility will improve after breast reduction as indicated by significant reduction of D-SEP latencies and increase of its amplitudes. Our results confirm an inverse relationship between breast size and sensibility, with improvement in sensibility after breast reduction.

Inflammation During Gestation Induced Spatial Memory and Learning Deficits: Attenuated by Physical Exercise in Juvenile Rats.

Gestational infections induced inflammation (GIII) is a cause of various postnatal neurological deficits in developing countries. Such intra uterine insults could result in persistent learning-memory disabilities. There are no studies elucidating the efficacy of adolescence exercise on spatial learning- memory abilities of young adult rats pre-exposed to inflammatory insult during fetal life. The present study addresses the efficacy of physical (running) exercise during adolescent period in attenuating spatial memory deficits induced by exposure to GIII in rats. Pregnant Wistar dams were randomly divided into control and lipopolysaccharide (LPS) groups, injected intra peritoneally (i.p) with saline (0.5ml) or lipopolysaccharide (LPS) (0.5mg/kg) on alternate days from gestation day 14 (GD 14) till delivery. After parturition, pups were divided into 3 groups (n=6/group) a) Sham control and LPS group divided into 2 subgroups- b) LPS and c) LPS exercise group. Running exercise was given only to LPS exercise group during postnatal days (PNDs) 30 to 60 (15min/day). Spatial learning and memory performance was assessed by Morris water maze test (MWM), on postnatal day 61 to 67 in all groups. Young rats pre-exposed to GIII and subjected to running exercise through juvenile period displayed significant decrease in latency to reach escape platform and spent significant duration in target quadrant in MWM test, compared to age matched LPS group. Results of the current study demonstrated that exercise through juvenile/adolescent period effectively mitigates gestational inflammation-induced cognitive deficits in young adult rats. Inflammation during gestation impairs offspring's spatial memory and learning abilities. Whereas, early postnatal physical exercise attenuates, to higher extent, cognitive impairment resulted from exposure to LPS induced inflammation during intrauterine growth period.

EVALUATION OF NEUROPHARMACOLOGICAL ACTIVITY OF PUNICA GRANATUM L. PEELS IN EXPERIMENTAL RATS

Extracts of peels of Punica granatum L. were screened for neuropharmacological activities viz. antianxiety, analgesic and learning and memory activities, using Elevated Plus Maze (EPM), Hot Plate Analgesiometer and Morris Water Maze, respectively. Aqueous extract of the peels (200mg/kg) and ethanolic extracts (200mg/kg and 400mg/kg) were administered by oral route for seven days. The control used was 1% Tween 80. Diazepam (4 mg/kg) and pentazocine (5 mg/kg) were used as standard drugs. Phytochemical analysis of the extracts was conducted. The rats receiving the ethanolic extract at a dose of 400mg/kg showed a significant increase in percentage open arm entries and percentage time spent in open arms in the EPM test thus indicating anti-anxiety activity. All the three extracts showed significant increase in reaction time on the hot plate analgesiometer and significant decrease in latency in the Morris Water Maze test, thus demonstrating analgesic activity and memory enhancement.

Abstract 4871: Obesity-mediated regulation of HGF/c-Met and reduced basal-like breast cancer latency in parous mice

Abstract Background: Epidemiologic and experimental data have shown that a full term pregnancy reduces breast cancer risk. While a full term pregnancy reduces risk for estrogen receptor positive (ER+) and luminal breast cancers, parity is associated with increased risk of basal-like breast cancer (BBC) subtype. BBC represents &amp;lt;10% of breast cancers, are highly aggressive, affecting primarily young and African-American women. Experimental studies have examined parity and obesity individually, but to date, the independent and joint effects of parity and obesity have not been dissected. Our previous work demonstrated that high fat diet-induced obesity significantly blunted BBC latency in nulliparous C3(1)-Tag mice, potentially through the hepatocyte growth factor (HGF)/c-Met oncogenic pathway. Since obesity and post-partum weight gain are sometimes difficult to parse out, we investigated the role of obesity in parous mice on BBC. Methods: Seven week old female C3(1)-TAg mice were placed with male mice for breeding. Males were removed at pregnancy and pups were removed immediately after birth. The mothers were then randomly assigned to diet groups to model post-partum obesity. Mice were fed control low fat diet (10% kcal from fat) or high fat diet (45% or 60% kcal from fat) at 10 weeks until sacrifice. Mice were monitored for fat accretion, tumor onset, and tumor progression. Plasma measures of cytokines and metabolic parameters were assessed. Immunohistochemical analyses for HGF, c-Met and F4/80 macrophage markers were performed. Results: Mice on both 45% and 60% diets gained significantly greater fat mass compared to mice remaining lean on 10% diet. Compared with nulliparous mice fed the same diets, parity induced significant decreases in latency in C3(1)-TAg mice fed 10% and 45% diets. 60% diet reduced latency in parous mice to the same extent as nulliparous mice fed 60% diet. Tumor burden and tumor aggressiveness were not regulated by obesity in parous mouse. Obesity-associated metabolic mediators and hormones such as insulin, estrogen, and progesterone were not significantly regulated however, leptin levels were elevated in 45%-fed mice compared to other groups. Plasma IL-6 was significantly elevated by obesity in parous mice. Importantly, the HGF/c-Met axis in normal mammary gland was elevated significantly by obesity and correlated with reduced tumor latency. Conclusions: In summary, our studies demonstrate that, similar to epidemiologic reports, parity in C3(1)-TAg mice alone dramatically reduced BBC latency compared to nulliparous mice. Obesity in parous mice did not reduce latency further than obesity alone, indicating that obesity and parity may work through similar pathways. Finally, obesity induced c-Met expression in normal mammary gland in parous mice, similar to our reports in nulliparous mice, implicating an interaction between the HGF/c-Met signaling pathway and obesity in the etiology of BBC. Citation Format: Sneha Sundaram, Alex J. Freemerman, Erin L. Kirk, Joseph A. Galanko, Kirk K. McNaughton, Katharine M. Bendt, David B. Darr, Melissa A. Troester, Liza Makowski. Obesity-mediated regulation of HGF/c-Met and reduced basal-like breast cancer latency in parous mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4871. doi:10.1158/1538-7445.AM2014-4871

Comparative Evaluation of Ethanolic Extracts of Bacopa monnieri, Evolvulus alsinoides, Tinospora cordifolia and their Combinations on Cognitive Functions in Rats

The effects of ethanolic extracts of whole plants of Bacopa monnieri (BME), Evolvulus alsinoides (EAE), Tinospora cordifolia (TCE) and their combinations in equal proportion [CEP-1 (BME+EAE), CEP-2 (BME+TCE), CEP-3 (EAE+TCE) and CEP-4 (BME+EAE+TCE)] were tested in amnesic rats using Radial arm maze task performance (RAM) and Barnes maze test at 200 mg/kg p.o. The latency to find food and target hole was observed in RAM and Barnes maze respectively. Cognitive dysfunction was induced by scopolamine (0.3 mg/kg i.p.) treatment. BME, EAE, TCE and their combinations of equal proportion (CEPs) showed significant decrease in latency to find food and target hole in RAM and Barnes maze respectively. Inter comparison among single extract alone treated groups revealed that BME treated animals showed significant difference as compared to EAE and TCE treated animals. All combinations of equal proportion (CEPs) of these extracts showed significant difference in latency to find food and target hole as compared to single extracts treated animals. CEP-1 showed significantly better effect as compared to CEP-2 and CEP-3. Significant difference in latency to find food and target hole was also present between CEP-2 and CEP-3. Effect of CEP-4 was found to be significantly better than CEP-1, CEP-2 and CEP-3 treated rats in both models. From present investigation, it was concluded that ethanolic extract of Bacopa monnieri, Evolvulus alsinoides and Tinospora cordifolia provided better nootropic effect when used in combination.