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Background:Parkinson’s Disease (PD) is characterized by alterations in cerebellum and basal ganglia functioning with corresponding motor deficits and neuropsychiatric symptoms. Involvement of oxidative dysfunction has been implicated for the progression of PD, and environmental neurotoxin exposure could influence such behavior and psychiatric pathology. Assessing dietary supplementation strategies with naturally occurring phytochemicals to reduce behavioral anomalies associated with neurotoxin exposure would have major clinical importance. The present investigation assessed the influence of Bacopa monneri (BM) on behaviors considered to reflect anxiety-like state and motor function as well as selected biochemical changes in brain regions of mice chronically exposed to ecologically relevant herbicide, paraquat (PQ).Materials & Methods:Male mice (4-week old, Swiss) were daily provided with oral supplements of standardized BM extract (200 mg/kg body weight/day; 3 weeks) and PQ (10 mg/kg, i.p. three times a week; 3 weeks).Results:We found that BM supplementation significantly reversed the PQ-induced reduction of exploratory behavior, gait abnormalities (stride length and mismatch of paw placement) and motor impairment (rotarod performance). In a separate study, BM administration prevented the reduction in dopamine levels and reversed cholinergic activity in brain regions important for motor (striatum) pathology. Further, in mitochondria, PQ-induced decrease in succinate dehydrogenase (SDH) activity and energy charge (MTT reduction), was restored with BM supplementation.Conclusion:These findings suggest that BM supplementation mitigates paraquat-induced behavioral deficits and brain oxidative stress in mice. However, further investigations would enable us to identify specific molecular mechanism by which BM influences behavioural pathology.

The increase in exposure to environmental neurotoxicants has contributed to the development of neurological disorders around the world such that neurodegenerative disease and neurodevelopmental disorders are becoming more common. The gut–brain axis is recognized as a crucial signaling bidirectional loop for the interactions between gut bacteria and the nervous system. New research indicating the role of the gut microbiome in linking environmental exposures and neurotoxic outcomes are starting to emerge. Here, we discuss microbial regulation of chemical biotransformation, generation of metabolic products, and immune responses as important areas for assessing the influence of the microbiome on neurotoxic outcomes. We additionally evaluate findings from animal studies on dietary strategies for manipulating the intestinal microbiota as a modifier of neurotoxicity, an outlook that can open novel avenues for mitigating neurotoxicity.

Women approximate one-third of the annual 2.8 million people in the United States who sustain traumatic brain injury (TBI). Several clinical reports support or refute that menstrual cycle-dependent fluctuations in sex hormones are associated with severity of persisting post-TBI symptoms. Previously, we reported late-onset sensory hypersensitivity to whisker stimulation that corresponded with changes in glutamate neurotransmission at 1-month following diffuse TBI in male rats. Here, we incorporated intact age-matched naturally cycling females into the experimental design while monitoring daily estrous cycle. We hypothesized that sex would not influence late-onset sensory hypersensitivity and associated in vivo amperometric extracellular recordings of glutamate neurotransmission within the behaviorally relevant thalamocortical circuit. At 28 days following midline fluid percussion injury (FPI) or sham surgery, young adult Sprague-Dawley rats were tested for hypersensitivity to whisker stimulation using the whisker nuisance task (WNT). As predicted, both male and female rats showed significantly increased sensory hypersensitivity to whisker stimulation after FPI, with females having an overall decrease in whisker nuisance scores (sex effect), but no injury and sex interaction. In males, FPI increased potassium chloride (KCl)-evoked glutamate overflow in primary somatosensory barrel cortex (S1BF) and ventral posteromedial nucleus of the thalamus (VPM), while in females the FPI effect was discernible only within the VPM. Similar to our previous report, we found the glutamate clearance parameters were not influenced by FPI, while a sex-specific effect was evident with female rats showing a lower uptake rate constant both in S1BF and VPM and longer clearance time (in S1BF) in comparison to male rats. Fluctuations in estrous cycle were evident among brain-injured females with longer diestrus (low circulating hormone) phase of the cycle over 28 days post-TBI. Together, these findings add to growing evidence indicating both similarities and differences between sexes in a chronic response to TBI. A better understanding of the influence of gonadal hormones on behavior, neurotransmission, secondary injury and repair processes after TBI is needed both clinically and translationally, with potential impact on acute treatment, rehabilitation, and symptom management.

Over 2.8 million traumatic brain injuries (TBIs) are reported in the United States annually, of which, over 75% are mild TBIs with diffuse axonal injury (DAI) as the primary pathology. TBI instigates a stress response that stimulates the hypothalamic-pituitary-adrenal (HPA) axis concurrently with DAI in brain regions responsible for feedback regulation. While the incidence of affective symptoms is high in both men and women, presentation is more prevalent and severe in women. Few studies have longitudinally evaluated the etiology underlying late-onset affective symptoms after mild TBI and even fewer have included females in the experimental design. In the experimental TBI model employed in this study, evidence of chronic HPA dysregulation has been reported at 2 months post-injury in male rats, with peak neuropathology in other regions of the brain at 7 days post-injury (DPI). We predicted that mechanisms leading to dysregulation of the HPA axis in male and female rats would be most evident at 7 DPI, the sub-acute time point. Young adult age-matched male and naturally cycling female Sprague Dawley rats were subjected to midline fluid percussion injury (mFPI) or sham surgery. Corticotropin releasing hormone, gliosis, and glucocorticoid receptor (GR) levels were evaluated in the hypothalamus and hippocampus, along with baseline plasma adrenocorticotropic hormone (ACTH) and adrenal gland weights. Microglial response in the paraventricular nucleus of the hypothalamus indicated mild neuroinflammation in males compared to sex-matched shams, but not females. Evidence of microglia activation in the dentate gyrus of the hippocampus was robust in both sexes compared with uninjured shams and there was evidence of a significant interaction between sex and injury regarding microglial cell count. GFAP intensity and astrocyte numbers increased as a function of injury, indicative of astrocytosis. GR protein levels were elevated 30% in the hippocampus of females in comparison to sex-matched shams. These data indicate sex-differences in sub-acute pathophysiology following DAI that precede late-onset HPA axis dysregulation. Further understanding of the etiology leading up to late-onset HPA axis dysregulation following DAI could identify targets to stabilize feedback, attenuate symptoms, and improve efficacy of rehabilitation and overall recovery.

Mild traumatic brain injury (TBI) often results in pathophysiological damage that can manifest as both acute and chronic neurological deficits. In an attempt to repair and reconnect disrupted circuits to compensate for loss of afferent and efferent connections, maladaptive circuitry is created and contributes to neurological deficits, including post-concussive symptoms. The TBI-induced pathology physically and metabolically changes the structure and function of neurons associated with behaviorally relevant circuit function. Complex neurological processing is governed, in part, by circuitry mediated by primary and modulatory neurotransmitter systems, where signaling is disrupted acutely and chronically after injury, and therefore serves as a primary target for treatment. Monitoring of neurotransmitter signaling in experimental models with technology empowered with improved temporal and spatial resolution is capable of recording in vivo extracellular neurotransmitter signaling in behaviorally relevant circuits. Here, we review preclinical evidence in TBI literature that implicates the role of neurotransmitter changes mediating circuit function that contributes to neurological deficits in the post-acute and chronic phases and methods developed for in vivo neurochemical monitoring. Coupling TBI models demonstrating chronic behavioral deficits with in vivo technologies capable of real-time monitoring of neurotransmitters provides an innovative approach to directly quantify and characterize neurotransmitter signaling as a universal consequence of TBI and the direct influence of pharmacological approaches on both behavior and signaling.

Environmental insults including pesticide exposure and their entry into the immature brain are of increased concern due to their developmental neurotoxicity. Several lines of evidence suggest that maternal gut microbiota influences in utero fetal development via modulation of host’s microbial composition with prebiotics. Hence we examined the hypothesis if inulin (IN) supplements during pregnancy in rats possess the potential to alleviate brain oxidative response and mitochondrial deficits employing a developmental model of rotenone (ROT) neurotoxicity. Initially, pregnant Sprague-Dawley rats were gavaged during gestational days (GDs) 6–19 with 0 (control), 10 (low), 30 (mid) or 50 (high) mg/kg bw/day of ROT to recapitulate developmental effects on general fetotoxicity (assessed by the number of fetuses, fetal body and placental weights), markers of oxidative stress and cholinergic activities in maternal brain regions and whole fetal-brain. Secondly, dams orally supplemented with inulin (2×/day, 2 g/kg/bw) on GD 0–21 were administered ROT (50 mg/kg, GD 6–19). IN supplements increased maternal cecal bacterial numbers that significantly corresponded with improved exploratory-related behavior among ROT administered rats. In addition, IN supplements improved fetal and placental weight on GD 19. IN diminished gestational ROT-induced increased reactive oxygen species levels, protein and lipid peroxidation biomarkers, and cholinesterase activity in maternal brain regions (cortex, cerebellum, and striatum) and fetal brain. Moreover, in the maternal cortex, mitochondrial assessment revealed IN protected against ROT-induced reduction in NADH cytochrome c oxidoreductase and ATPase activities. These data suggest a potential role for indigestible oligosaccharides in reducing oxidative stress-mediated developmental origins of neurodegenerative disorders.

Drosophilae are emerging as a valuable model to study traumatic brain injury (TBI)-induced secondary injury cascades that drive persisting neuroinflammation and neurodegenerative pathology that imposes significant risk for long-term neurological deficits. As in mammals, TBI in Drosophila triggers axonal injury, metabolic crisis, oxidative stress, and a robust innate immune response. Subsequent neurodegeneration stresses quality control systems and perpetuates an environment for neuroprotection, regeneration, and delayed cell death via highly conserved cell signaling pathways. Fly injury models continue to be developed and validated for both whole-body and head-specific injury to isolate, evaluate, and modulate these parallel pathways. In conjunction with powerful genetic tools, the ability for longitudinal evaluation, and associated neurological deficits that can be tested with established behavioral tasks, Drosophilae are an attractive model to explore secondary injury cascades and therapeutic intervention after TBI. Here, we review similarities and differences between mammalian and fly pathophysiology and highlight strategies for their use in translational neurotrauma research.

Scope Traumatic brain injury (TBI) compromises neuronal function required for hippocampal synaptic plasticity and cognitive function. Despite the high consumption of blueberries, information about its effects on brain plasticity and function under conditions of brain trauma is limited. The efficacy of dietary blueberry (BB) supplementation to mitigate the effects of TBI on plasticity markers and associated behavioral function in a rodent model of concussive injury are assessed. Methods and results Rats were maintained on a diet supplemented with blueberry (BB, 5% w/w) for 2 weeks after TBI. It is found that BB supplementation mitigated a loss of spatial learning and memory performance after TBI, and reduced the effects of TBI on anxiety-like behavior. BB supplementation prevents a reduction of molecules associated with the brain-derived neurotrophic factor (BDNF) system action on learning and memory such as cyclic-AMP response element binding factor (CREB), calcium/calmodulin-dependent protein kinase II (CaMKII). In addition, BB supplementation reverses an increase of the lipid peroxidation byproduct 4-hydroxy-nonenal (4-HNE) after TBI. Importantly, synaptic and neuronal signaling regulators change in proportion with the memory performance, suggesting an association between plasticity markers and behavior. Conclusion Data herein indicate that BB supplementation has a beneficial effect in mitigating the acute aspects of the TBI pathology.

Bacopa monnieri (BM), an ayurvedic medicinal plant, has attracted considerable interest owing to its diverse neuropharmacological properties. Epidemiological studies have shown significant correlation between paraquat (PQ) exposure and increased risk for Parkinson's disease in humans. In this study, we examined the propensity of standardized extract of BM to attenuate acute PQ-induced oxidative stress, mitochondrial dysfunctions, and neurotoxicity in the different brain regions of prepubertal mice.To test this hypothesis, prepubertal mice provided orally with standardized BM extract (200 mg/kg body weight/day for 4 weeks) were challenged with an acute dose (15 mg/kg body weight, intraperitoneally) of PQ after 3 hours of last dose of extract. Mice were sacrificed after 48 hours of PQ injection, and different brain regions were isolated and subjected to biochemical determinations/quantification of central monoamine (dopamine, DA) levels (by high-performance liquid chromatography).Oral supplementation of BM for 4 weeks resulted in significant reduction in the basal levels of oxidative markers such as reactive oxygen species (ROS), malondialdehyde (MDA), and hydroperoxides (HP) in various brain regions. PQ at the administered dose elicited marked oxidative stress within 48 hours in various brain regions of mice. However, BM prophylaxis significantly improved oxidative homeostasis by restoring PQ-induced ROS, MDA, and HP levels and also by attenuating mitochondrial dysfunction. Interestingly, BM supplementation restored the activities of cholinergic enzymes along with the restoration of striatal DA levels among the PQ-treated mice.Based on these findings, we infer that BM prophylaxis renders the brain resistant to PQ-mediated oxidative perturbations and thus may be better exploited as a preventive approach to protect against oxidative-mediated neuronal dysfunctions.

Background: Obstructive sleep apnea (OSA) is a sleep-associated breathing disorder, which left untreated can cause severe morbidities or even mortality. The recommended treatment strategy for moderate-to-severe OSA is continuous positive airway pressure (CPAP). The optimal pressure required for OSA can be measured by either manual CPAP titration or auto-CPAP titration study. Objective: To assess the efficacy of auto-PAP titration for OSA patients. Methodology: This was a cross-sectional study conducted on Pulmonary Medicine Sleep Lab at Amrita Institute of Medical Sciences, Kochi. Fifty patients who have undergone full-night polysomnography and followed with auto-PAP titration are included in the study. The research was approved by the institutional ethics committee. Results: In the study cohort, 50% showed optimal titration, 40% good titration, 10% adequate titration and none in unacceptable category. The results showed that auto-PAP usage has good result in moderate-to-severe OSA. Conclusion: Unattended auto-PAP titration seems to be highly effective modality which can be considered as an alternative to attended CPAP titration, thus reducing labor intensiveness and cost.

BACKGROUND: Tomato seeds, amajor by-product fromthe food processing industry, constitute a rich source of bioactives and a large population consumes tomato (either in raw or cooked form). In the present study, initially we assessed the antioxidant activity of aqueous extract of tomato seeds (TSE) in selected chemical systems and further explored the neuroprotective effects of TSE utilising the rotenone (ROT)model of neurotoxicity in Drosophila. RESULTS: Adultmale flies (Oregon K) were fed TSE-enriched medium (0.1–0.2%) with or without ROT (500

Accumulating evidence suggests that the developing brain is more susceptible to a variety of chemicals. Recent studies have shown a link between the enteric microbiota and brain function. While supplementation of non-digestible oligosaccharides during pregnancy has been demonstrated to positively influence human health mediated through stimulation of beneficial microbiota, our understanding on their neuromodulatory propensity is limited. In the present study, our primary focus was to examine whether supplementation of inulin (a well known fructan) during gestation can abrogate acrylamide (ACR)-induced oxidative impairments and neurotoxicity in maternal and fetal brain of rats. Initially, in a dose-determinative study, we recapitulated the impact of ACR exposure during gestation days (GD 6-19) on gestational parameters, extent of oxidative impairments in brain (maternal/fetal), cholinergic function and neurotoxicity. Subsequently, pregnant rats orally (gavage) administered with inulin (IN, 2 g/kg/day in two equal installments) supplements during gestation days (GD 0-19) were exposed to ACR (200 ppm) in drinking water. IN supplements significantly attenuated ACR-induced changes in exploratory activity (reduced open field exploration) measured on GD 14. Further, IN restored the placental weights among ACR exposed dams. Analysis of biochemical markers revealed that IN supplements effectively offset ACR associated oxidative stress not only in the maternal brain, but in the fetal brain as well. Elevated levels of protein carbonyls in maternal brain regions were completely normalized with IN supplements. More importantly, IN supplements significantly augmented the number of Bifidobacteria in the cecum of ACR rats which correlated well with the neurorestorative effect as evidenced by restored dopamine levels in the maternal cortex and fetal brain acetylcholinesterase activity among ACR-exposed dams. Further, IN supplements also conferred significant protection against mitochondrial dysfunction induced by ACR in both milieus. Although the precise mechanism/s by which IN supplements during pregnancy attenuate ACR induced neurotoxic impact merits further investigations, we hypothesize that it may mediate through enhanced enteric microbiota and abrogation of oxidative stress. Further, our study provides an experimental approach to explore the neuroprotective role of prebiotic oligosaccharides during pregnancy in reducing the adverse impact of developmental neurotoxicants.

Metabolic dysfunction accompanying traumatic brain injury (TBI) severely impairs the ability of injured neurons to comply with functional demands. This limits the success of rehabilitative strategies by compromising brain plasticity and function, and highlights the need for early interventions to promote energy homeostasis. We sought to examine whether the TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) normalizes brain energy deficits and restablishes more normal patterns of functional connectivity, while enhancing the effects of exercise during post-TBI period. Moderate fluid percussion injury (FPI) was performed and 7,8-DHF (5 mg/kg, i.p.) was administered in animals subjected to FPI that either had access to voluntary wheel running for 7 days after injury or were sedentary. Compared to sham-injured controls, TBI resulted in reduced hippocampal activation of the BDNF receptor TrkB and associated CREB, reduced levels of plasticity markers GAP-43 and Syn I, as well as impaired memory as indicated by the Barnes maze task. While 7,8-DHF treatment and exercise individually mitigated TBI-induced effects, administration of 7,8-DHF concurrently with exercise facilitated memory performance and augmented levels of markers of cell energy metabolism viz., PGC-1α, COII and AMPK. In parallel to these findings, resting-state functional MRI (fMRI) acquired at 2 weeks after injury showed that 7,8-DHF with exercise enhanced hippocampal functional connectivity, and suggests 7,8-DHF and exercise to promote increases in functional connectivity. Together, these findings indicate that post-injury 7,8-DHF treatment promotes enhanced levels of cell metabolism, synaptic plasticity in combination with exercise increases in brain circuit function that facilitates greater physical rehabilitation after TBI.

Variation of the common carotid artery, including high origin, rare absence, low bifurcation & also anomolous origins of common carotid artery are very common. Knowledge of carotid bifurcation is important for vascular surgical procedures, such as carotid endarterectomy or radical neck dissection, catheterization and aneurysms 1 . The aim of this study was to describe the level of common carotid artery bifurcation. 50 adult cadavers were dissected and variation in pattern of common carotid artery bifurcation were noted. During radical neck surgeries, the common carotid arteries are important landmarks, defining the plane of the dissection .Evaluation of the carotid bifurcation level can be done with non invasive techniques and external anatomical landmarks can be clinically useful in predicting the bifurcation level of the carotid artery. Accurate level of bifurcation can be devised by dissection method in nonliving. Increase variations in the branching patterns may increase the risk of vascular accidents during surgical procedures in the neck and also angiographic aberrations 3

Prebiotic oligosaccharides are demonstrated to confer a wide spectrum of physiological benefits during pregnancy. In view of this, focused attempts are being directed towards understanding their role as modulators of brain chemistry and behavior. Epidemiological studies have identified that exposure to neurotoxins during prenatal/early life can profoundly impact neurodevelopment/function. In this context, we have tested the hypothesis that a combination of prebiotic supplements during gestation has the propensity to attenuate acrylamide (ACR) induced oxidative impairments, mitochondrial dysfunction and neurotoxicity in maternal and fetal brain of rats. To achieve this, pregnant dams given oral supplements of a combination of fructo- and xylooligosaccharides (FOS + XOS, 3 g/kg/day) during gestation days (GD 0–19) were exposed to ACR (200 ppm in drinking water, GD 6–19). The behavioral analysis revealed that ACR dams fed prebiotics displayed higher exploratory behavior in the open field test. The prenatal evaluation showed that ACR-induced decrements of placental/fetal weights were markedly restored with prebiotic feeding. Prebiotics significantly offset markers of oxidative stress, restored enzymic antioxidants, cholinergic and mitochondrial function in the maternal and fetal brain. Concomitantly, prebiotics restored ACR-induced depletion in the levels of dopamine and γ-aminobutyric acid in the maternal cortex that positively correlated with cecal bacterial numbers. Collectively, these data suggest that prenatal prebiotic oligosaccharide supplements protect developing brain against oxidative stress-mediated neurotoxicity. While the underlying mechanism/s by which prebiotics abrogate the impact of neurotoxicants in the developing brain merits further studies, we speculate that it may be mediated predominantly through attenuation of oxidative stress and proliferation of enteric microbiota.