Key Performance Indicators: A Framework for Allied Healthcare Educational Institutions.

Background: Performance evaluation in the allied healthcare education sector is complex, making it essential for policymakers and managers to approach it comprehensively and thoughtfully to understand their performance. Hence, the development and monitoring of Key Performance Indicators (KPIs) in this domain must be considered one of the key priorities for the policymakers in AHIs. Aim: This study aims to develop a framework for the AHIs to extract and profile the indicators, measure, and report the results appropriately. Methods: The authors adopted a general review of the literature approach to study the primary goals of the institutional KPI framework, emphasizing the need for benchmarking while implementing KPIs and how to track performance using a KPI dashboard. Results: The study provides the scope, relevant KPI categories, and a list of KPIs for evaluating the effectiveness of allied healthcare programs. The study findings also emphasized the need for benchmarking the KPIs and establishing a KPI dashboard while measuring and monitoring performance. Conclusion: KPIs are considered an invaluable tool that contributes immensely to the performance monitoring process of AHIs, irrespective of the specialties. This helps to identify and guide AHIs for developing KPIs and the associated minimum data set to measure organizational performance and monitor the quality of teaching and learning. In addition, the KPI framework reported in this study is a tool to assist performance monitoring that can subsequently contribute to the overall quality of AHIs.

The long-term effects of COVID-19 on pulmonary status and quality of life.

Background: Few studies have looked at how SARS-CoV-2 affects pulmonary function, exercise capacity, and health-related quality of life over time. The purpose of this study was to evaluate these characteristics in post COVID-19 subjects 1 year after recovery. Methods: The study included two groups. The case group included post COVID-19 subjects who had recovered after a year, and the control group included healthy participants who had never tested positive for COVID-19. Results: The study screened 90 participants, 42 of whom met the eligibility criteria. The findings revealed that the majority of post COVID-19 subjects had relatively normal lung function 1-year post-recovery. A significant reduction in DLCO (B/P%) was observed in the case group vs. control. The exercise capacity test revealed a clinically significant difference in distance walked and a significant difference in the dyspnea post-walk test in the case group compared to the control group. The case group's health-related quality of life domain scores were significantly affected in terms of energy/fatigue, general health, and physical function. Conclusions: The post COVID-19 subjects were shown to have well-preserved lung function after 1 year. However, some degree of impairment in diffusion capacity, exercise capacity, and health-related quality of life remained.

Outcomes after Conversion from Video-Assisted Thoracoscopic Lobectomy to Thoracotomy.

BACKGROUND: Lung cancer resections are increasingly being performed via video-assisted thoracoscopic surgery (VATS). Conversion to thoracotomy can occur for many reasons and may affect outcomes. The objective of this study was to investigate the impact of VATS conversion on short- and mid-term outcomes and identify reasons for conversion. METHODS: Consecutive patients undergoing lobectomy for primary non-small cell lung cancer between 2012 and 2019 in a single UK center were included. Primary outcomes were 90-day mortality, intraoperative conversion, and overall survival. Reasons for conversion were defined as bleeding or nonbleeding. Outcomes were compared between groups using univariable analysis. Multivariable logistic regression analysis was performed to identify risk factors for conversion. RESULTS: A total of 2,622 patients were included with 20.6% (n = 541) completing surgery via VATS and 79.4% (n = 2,081) via thoracotomy. The rate of completed VATS surgery increased significantly over time (2012: 6.9%, 2019: 55.1%, p < 0.001). Overall conversion rate was 14.3% (n = 90/631) and has reduced significantly over time (p < 0.001). The rate of conversion due to intraoperative bleeding was 31.1% (n = 28/90). Obesity, male sex, and stage III disease were independent risk factors for conversion. The 90-day mortality rate after conversion was not significantly different from the rate for planned thoracotomy (3.3 vs. 3.4%, p = 0.987). There was no significant difference in overall survival between patients experiencing intraoperative conversion and those undergoing planned thoracotomy (p = 0.135). CONCLUSION: This study demonstrates comparable outcomes for patients undergoing conversion from VATS to those undergoing planned surgery via thoracotomy. It remains unclear if reason for conversion is associated with outcomes.

Effects of isoflurane and urethane anesthetics on glutamate neurotransmission in rat brain using in vivo amperometry.

BACKGROUND: Aspects of glutamate neurotransmission implicated in normal and pathological conditions are predominantly evaluated using in vivo recording paradigms in rats anesthetized with isoflurane or urethane. Urethane and isoflurane anesthesia influence glutamate neurotransmission through different mechanisms; however, real-time outcome measures of potassium chloride (KCl)-evoked glutamate overflow and glutamate clearance kinetics have not been compared within and between regions of the brain. In order to maintain rigor and reproducibility within the literature between the two most common methods of anesthetized in vivo recording of glutamate, we compared glutamate signaling as a function of anesthesia and brain region in the rat strain most used in neuroscience. METHODS: In the following experiments, in vivo amperometric recordings of KCl-evoked glutamate overflow and glutamate clearance kinetics (uptake rate and T80) in the cortex, hippocampus, and thalamus were performed using glutamate-selective microelectrode arrays (MEAs) in young adult male, Sprague-Dawley rats anesthetized with either isoflurane or urethane. RESULTS: Potassium chloride (KCl)-evoked glutamate overflow was similar under urethane and isoflurane anesthesia in all brain regions studied. Analysis of glutamate clearance determined that the uptake rate was significantly faster (53.2%, p < 0.05) within the thalamus under urethane compared to isoflurane, but no differences were measured in the cortex or hippocampus. Under urethane, glutamate clearance parameters were region-dependent, with significantly faster glutamate clearance in the thalamus compared to the cortex but not the hippocampus (p < 0.05). No region-dependent differences were measured for glutamate overflow using isoflurane. CONCLUSIONS: These data support that amperometric recordings of KCl-evoked glutamate under isoflurane and urethane anesthesia result in similar and comparable data. However, certain parameters of glutamate clearance can vary based on choice of anesthesia and brain region. In these circumstances, special considerations are needed when comparing previous literature and planning future experiments.

Liver acts as a metabolic gate for the traumatic brain injury pathology: Protective action of thyroid hormone.

Clinical evidence indicates that injury to the brain elicits systemic metabolic disturbances that contributes to the brain pathology. Since dietary fructose is metabolized in the liver, we explored mechanisms by which traumatic brain injury (TBI) and dietary fructose influence liver function and their possible repercussions to brain. Consumption of fructose contributed to the detrimental effects of TBI on liver operation, in terms of glucose and lipid metabolism, de novo lipogenesis, lipid peroxidation. Thyroid hormone (T4) is metabolized in the liver and found that T4 supply improved lipid metabolism by reducing de novo lipogenesis, lipid accumulation, lipogenic enzymes (ACC, AceCS1, FAS), lipid peroxidation in liver in response to fructose and fructose-TBI. T4 supply also helped to normalize glucose metabolism and improve insulin sensitivity. Furthermore, T4 counteracted elevations of the pro-inflammatory cytokines, Tnfα and Mcp-1 after TBI and/or fructose intake in liver and circulation. T4 also exerted an effect on isolated primary hepatocytes by potentiating phosphorylation of AMPKα and AKT substrate, AS160, leading to increased glucose uptake. In addition, T4 restored the metabolism of DHA in the liver disrupted by TBI and fructose, adding important information to optimize the action of DHA in therapeutics. The overall evidence seems to indicate that the liver works as a gate for the regulation of the effects of brain injury and foods on brain pathologies.

Effects of isoflurane and urethane anesthetics on glutamate neurotransmission in rat brain using in vivo amperometry.

Aspects of glutamate neurotransmission implicated in normal and pathological conditions are often evaluated using in vivo recording paradigms in rats anesthetized with isoflurane or urethane. Urethane and isoflurane anesthesia influence glutamate neurotransmission through different mechanisms; however real-time outcome measures of potassium chloride (KCl)-evoked glutamate overflow and glutamate clearance kinetics have not been compared within and between regions of the brain. In the following experiments, in vivo amperometric recordings of KCl-evoked glutamate overflow and glutamate clearance kinetics (uptake rate and T80) in the cortex, hippocampus and thalamus were performed using glutamate-selective microelectrode arrays (MEAs) in young adult male, Sprague-Dawley rats anesthetized with isoflurane or urethane. Potassium chloride (KCl)-evoked glutamate overflow was similar under urethane and isoflurane anesthesia in all brain regions studied. Analysis of glutamate clearance determined that the uptake rate was significantly faster (53.2%, p<0.05) within the thalamus under urethane compared to isoflurane, but no differences were measured in the cortex or hippocampus. Under urethane, glutamate clearance parameters were region dependent, with significantly faster glutamate clearance in the thalamus compared to the cortex but not the hippocampus (p<0.05). No region dependent differences were measured for glutamate overflow using isoflurane. These data support that amperometric recordings of glutamate under isoflurane and urethane anesthesia result in mostly similar and comparable data. However, certain parameters of glutamate uptake vary based on choice of anesthesia and brain region. Special considerations must be given to these areas when considering comparison to previous literature and when planning future experiments.

Aging with TBI vs. Aging: 6-month temporal profiles for neuropathology and astrocyte activation converge in behaviorally relevant thalamocortical circuitry of male and female rats.

Traumatic brain injury (TBI) manifests late-onset and persisting clinical symptoms with implications for sex differences and increased risk for the development of age-related neurodegenerative diseases. Few studies have evaluated chronic temporal profiles of neuronal and glial pathology that include sex as a biological variable. After experimental diffuse TBI, late-onset and persisting somatosensory hypersensitivity to whisker stimulation develops at one-month post-injury and persists to at least two months post-injury in male rats, providing an in vivo model to evaluate the temporal profile of pathology responsible for morbidity. Whisker somatosensation is dependent on signaling through the thalamocortical relays of the whisker barrel circuit made up of glutamatergic projections between the ventral posteromedial nucleus of the thalamus (VPM) and primary somatosensory barrel cortex (S1BF) with inhibitory (GABA) innervation from the thalamic reticular nucleus (TRN) to the VPM. To evaluate the temporal profiles of pathology, male and female Sprague Dawley rats ( n = 5-6/group) were subjected to sham surgery or midline fluid percussion injury (FPI). At 7-, 56-, and 168-days post-injury (DPI), brains were processed for amino-cupric silver stain and glial fibrillary acidic protein (GFAP) immunoreactivity, where pixel density of staining was quantified to determine the temporal profile of neuropathology and astrocyte activation in the VPM, S1BF, and TRN. FPI induced significant neuropathology in all brain regions at 7 DPI. At 168 DPI, neuropathology remained significantly elevated in the VPM and TRN, but returned to sham levels in the S1BF. GFAP immunoreactivity was increased as a function of FPI and DPI, with an FPI × DPI interaction in all regions and an FPI × Sex interaction in the S1BF. The interactions were driven by increased GFAP immunoreactivity in shams over time in the VPM and TRN. In the S1BF, GFAP immunoreactivity increased at 7 DPI and declined to age-matched sham levels by 168 DPI, while GFAP immunoreactivity in shams significantly increased between 7 and 168 days. The FPI × Sex interaction was driven by an overall greater level of GFAP immunoreactivity in FPI males compared to FPI females. Increased GFAP immunoreactivity was associated with an increased number of GFAP-positive soma, predominantly at 7 DPI. Overall, these findings indicate that FPI, time post-injury, sex, region, and aging with injury differentially contribute to chronic changes in neuronal pathology and astrocyte activation after diffuse brain injury. Thus, our results highlight distinct patterns of pathological alterations associated with the development and persistence of morbidity that supports chronic neuropathology, especially within the thalamus. Further, data indicate a convergence between TBI-induced and age-related pathology where further investigation may reveal a role for divergent astrocytic phenotypes associated with increased risk for neurodegenerative diseases.

Physical Exercise as a Modulator of Vascular Pathology and Thrombin Generation to Improve Outcomes After Traumatic Brain Injury.

Disruption of the blood-brain barrier and occurrence of coagulopathy after traumatic brain injury (TBI) have important implications for multiple secondary injury processes. Given the extent of post-traumatic changes in neuronal function, significant alterations in some targets, such thrombin (a protease that plays a physiological role in maintaining blood coagulation), play an important role in TBI-induced pathophysiology. Despite the magnitude of thrombin in synaptic plasticity being concentration-dependent, the mechanisms underlying TBI have not been fully elucidated. The understanding of this post-injury neurovascular dysregulation is essential to establish scientific-based rehabilitative strategies. One of these strategies may be supporting physical exercise, considering its relevance in reducing damage after a TBI. However, there are caveats to consider when interpreting the effect of physical exercise on neurovascular dysregulation after TBI. To complete this picture, this review will describe how the interactions established between blood-borne factors (such as thrombin) and physical exercise alter the TBI pathophysiology.

Drosophila as a model to explore secondary injury cascades after traumatic brain injury.

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.

Sex-Dependent Pathology in the HPA Axis at a Sub-acute Period After Experimental Traumatic Brain Injury.

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.

Traumatic Brain Injury-Induced Sex-Dependent Changes in Late-Onset Sensory Hypersensitivity and Glutamate Neurotransmission.

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.

Approaches to Monitor Circuit Disruption after Traumatic Brain Injury: Frontiers in Preclinical Research.

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.

Blueberry Supplementation Mitigates Altered Brain Plasticity and Behavior after Traumatic Brain Injury in Rats.

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 Supplements Offset Paraquat-Induced Behavioral Phenotype and Brain Oxidative Pathways in Mice.

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.

Oral supplements of inulin during gestation offsets rotenone-induced oxidative impairments and neurotoxicity in maternal and prenatal rat brain.

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.

7,8-Dihydroxyflavone facilitates the action exercise to restore plasticity and functionality: Implications for early brain trauma recovery.

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 reestablishes 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 (5mg/kg, i.p.) was administered in animals subjected to FPI that either had access to voluntary wheel running for 7days 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 2weeks 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.

Standardized Bacopa monnieri extract ameliorates acute paraquat-induced oxidative stress, and neurotoxicity in prepubertal mice brain.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. DISCUSSION: 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.

Aqueous extract of tomato seeds attenuates rotenone-induced oxidative stress and neurotoxicity in Drosophila melanogaster.

BACKGROUND: Tomato seeds, a major by-product from the 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: Adult male flies (Oregon K) were fed TSE-enriched medium (0.1-0.2%) with or without ROT (500 µmol L(-1)) for 7 days. The propensity of TSE to protect flies against ROT-induced lethality, locomotor phenotype, oxidative stress and neurotoxicity was investigated. TSE offered marked protection against ROT-induced mortality, while survivors exhibited improved locomotor phenotype. TSE significantly attenuated ROT-induced oxidative stress, mitochondrial dysfunctions, protein carbonyls content, restored the cholinergic function and dopamine levels. CONCLUSION: We hypothesise that the efficacy of tomato seed extract to attenuate ROT-mediated neurotoxicity may be largely related to the combined antioxidant activity of bioactives resulting in abrogation of oxidative stress and mitochondrial dysfunction. More importantly, our approach provides an experimental paradigm to rapidly assess the potential neuroprotective effects of common dietary components employing Drosophila, since it corroborates previous evidence in a mouse model.