Kumar Vaibhav | Amity University Rajasthan (original) (raw)
Papers by Kumar Vaibhav
Therapeutic Applications of Honey and its Phytochemicals, 2020
Honey is one of the most nutritional natural products that not only provides us healthy nutrition... more Honey is one of the most nutritional natural products that not only provides us healthy nutrition but also has a potential to be an alternative treatment option for different pathologies from microbial infection to metabolic disease. Honey is a byproduct of flower syrup produced by honeybees and possesses an intricate chemical composition that varies with botanical sources and geographical locations. This chapter is aimed to provide readers an understanding of complex composition, biological activities, adverse effect, and therapeutic benefits of honey. Honey possesses many biological activities, such as antioxidant, anti-microbial, anti-inflammatory, anti-proliferative, anti-cancer, and anti-metastatic effects, suggesting potential therapeutic roles in many human pathologies. Flavonoids and polyphenols in honey are the two active ingredients, which are of therapeutic importance in many diseases. In conclusion, honey may be developed as a natural therapeutic agent for many pathologies, and extensive studies are therefore recommended.
Journal of Cannabis Research, 2021
Background Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome who... more Background Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experim...
Biomedicines, 2020
Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for... more Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative stress, and inflammatory cascades which lead to chronic pathology. Little can be done to treat the mechanical damage that occurs during the primary insult of a TBI; however, secondary injury mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, oxidative stress, and cell death, can be targeted by therapeutic interventions. Elucidating the many mechanisms underlying secondary injury and studying targets of neuroprotective therapeutic agents is critical for developing new treatments. Therefore, we present a review on the molecular events following TBI from inflammation to programmed cell death and discuss current research and the lates...
Journal of Biochemical and Molecular Toxicology, 2020
Pesticides are globally used to eliminate pests from crops and plants. The increased use of pesti... more Pesticides are globally used to eliminate pests from crops and plants. The increased use of pesticides has posed a serious threat to human health. This study evaluates the effects of pesticide exposure on pregnancy outcomes in tea garden workers (TGW). The acetylcholinesterase (AChE) activity was measured in the maternal blood, placenta, and cord blood of TGW and housewives (HWs). The placental structure and expression of hypoxia‐inducible factor (HIF)‐1α were also analyzed in TGW and HW groups delivering low birth weight (LBW) and normal birth weight (NBW) babies. A significantly decreased AChE activity was observed in maternal blood and cord blood in TGW as compared with HW in the LBW group. However, it did not change significantly in the NBW group (p < .05). The adjusted regression analysis of birth outcomes (birth weight, head circumference, infant's length, and ponderal index) revealed a significant and positive association with the levels of AChE activity in maternal blood, placenta, and cord blood in TGW (p < .05). The histological analysis showed significantly higher placental syncytial knots, chorangiosis, fibrinoid deposition, necrosis, and stromal fibrosis in the LBW group of TGW. Microinfarction, increased fibrinoid deposition, and atypical villi characteristics, such as mushroom‐like structures, were observed during scanning electron microscopy along with increased HIF‐1α expression in placental tissues of TGW exposed to pesticides. Results suggest that occupational pesticide exposure during pregnancy may decrease AChE activity and cause in utero pathological changes accompanied by an increased HIF‐1α expression, which also contributes to placental insufficiency and fetal growth restriction.
Stroke, 2019
Background and Purpose: There is presently no specific therapy for the treatment of VCID. We repo... more Background and Purpose: There is presently no specific therapy for the treatment of VCID. We reported that daily C-RIC (4mo) is effective in young mice by improving cerebral blood flow (CBF), minimizing white matter (WM) damage and improving functional outcomes in Bilateral Carotid Artery Stenosis model (BCAS.) The purpose of this study was to evaluate whether 4 months (4 MO-C-RIC) is effective in male and female aged mouse and if the treatment effects are durable out to 6MOS. Methods: Microcoil induced BCAS model was used to induce chronic hypoperfusion. Adult C57BL/6 both male & female mice (14-months ) were randomly assigned to 3-different groups (N=10), and subjected to Sham, BCAS+sham RIC, BCAS+RIC. C-RIC was started 7d post-surgery daily for 4MOs. Behavioral test and CBF was performed at 1, 4 and 6MO after BCAS and Sham surgery. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for mo...
Traumatic brain injury (TBI) is a major source of worldwide morbidity and mortality. Patients suf... more Traumatic brain injury (TBI) is a major source of worldwide morbidity and mortality. Patients suffering from TBI exhibit a higher susceptibility to bone loss and an increased rate of bone fractures; however, the underlying mechanisms remain poorly defined. Herein, we observed significantly lower bone quality and elevated levels of inflammation in bone and bone marrow niche after controlled cortical impact-induced TBI in in-vivo CD-1 mice. Further, we identified dysregulated NFB signaling, an established mediator of osteoclast differentiation and bone loss, within the bone marrow niche of TBI mice. Ex vivo studies revealed increased osteoclast differentiation in bone marrow-derived cells from TBI mice, as compared to sham injured mice. Finally, we found bone marrow derived extracellular vesicles (EVs) from TBI mice enhanced the colony forming ability and osteoclast differentiation efficacy of bone marrow cells and activated NFB signaling genes in bone marrow-derived cells. Taken to...
The Journal of experimental medicine, Jan 6, 2018
Spontaneous intracerebral hemorrhage (ICH) produces the highest acute mortality and worst outcome... more Spontaneous intracerebral hemorrhage (ICH) produces the highest acute mortality and worst outcomes of all stroke subtypes. Hematoma volume is an independent determinant of ICH patient outcomes, making clot resolution a primary goal of clinical management. Herein, remote-limb ischemic post-conditioning (RIC), the repetitive inflation-deflation of a blood pressure cuff on a limb, accelerated hematoma resolution and improved neurological outcomes after ICH in mice. Parabiosis studies revealed RIC accelerated clot resolution via a humoral-mediated mechanism. Whereas RIC increased anti-inflammatory macrophage activation, myeloid cell depletion eliminated the beneficial effects of RIC after ICH. Myeloid-specific inactivation of the metabolic regulator, AMPKα1, attenuated RIC-induced anti-inflammatory macrophage polarization and delayed hematoma resolution, providing a molecular link between RIC and immune activation. Finally, chimera studies implicated myeloid CD36 expression in RIC-media...
American journal of physiology. Renal physiology, Jan 13, 2018
Hallmark features of acute kidney injury (AKI) include mobilization of immune and inflammatory me... more Hallmark features of acute kidney injury (AKI) include mobilization of immune and inflammatory mechanisms culminating in tissue injury. Emerging information indicates heterogeneity of neutrophils with pro- and anti-inflammatory functions (N1 and N2, respectively). Also, regulatory T-17 (Treg17) cells curtail Th-17-mediated pro-inflammatory responses. However, the status of Treg17 cells and neutrophil phenotypes in AKI are not established. Further, cannabidiol exerts immunoregulatory effects but its impact on Treg17 cells and neutrophil subtypes is not established. Thus, we examined the status of Treg17 cells and neutrophil subtypes in AKI and determined whether cannabidiol favors regulatory neutrophils and T cells accompanied with renoprotection. Accordingly, mice were subjected to bilateral renal ischemia-reperfusion injury (IRI), without or with cannabidiol treatment; thereafter, kidneys were processed for flow cytometry analyses. Renal IRI increased N1 and Th-17 but reduced N2 an...
Translational stroke research, Oct 28, 2017
Over 700 drugs have failed in stroke clinical trials, an unprecedented rate thought to be attribu... more Over 700 drugs have failed in stroke clinical trials, an unprecedented rate thought to be attributed in part to limited and isolated testing often solely in "young" rodent models and focusing on a single secondary injury mechanism. Here, extracellular vesicles (EVs), nanometer-sized cell signaling particles, were tested in a mouse thromboembolic (TE) stroke model. Neural stem cell (NSC) and mesenchymal stem cell (MSC) EVs derived from the same pluripotent stem cell (PSC) line were evaluated for changes in infarct volume as well as sensorimotor function. NSC EVs improved cellular, tissue, and functional outcomes in middle-aged rodents, whereas MSC EVs were less effective. Acute differences in lesion volume following NSC EV treatment were corroborated by MRI in 18-month-old aged rodents. NSC EV treatment has a positive effect on motor function in the aged rodent as indicated by beam walk, instances of foot faults, and strength evaluated by hanging wire test. Increased time w...
Biochimica et biophysica acta, Oct 19, 2017
Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. D... more Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI. In this review, we explore the burgeoning evidence implicating the acute release of damage associated molecular patterns (DAMPs), such as adenosine 5'-triphosphate (ATP), high mobility group box protein 1 (HMGB1), S100 proteins, and hyaluronic acid in the initiation of progressive neurological injury, including white matter loss after TBI. The role that pattern recognition receptors...
Journal of immunology (Baltimore, Md. : 1950), May 24, 2017
Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortal... more Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortality and poor long-term outcomes. Increasing evidence suggests an important, yet poorly defined, role for the immune system in the development of secondary neurologic injury over the days and weeks following a TBI. In this study, we tested the hypothesis that peripheral macrophage infiltration initiates long-lasting adaptive immune responses after TBI. Using a murine controlled cortical impact model, we used adoptive transfer, transgenic, and bone marrow chimera approaches to show increased infiltration and proinflammatory (classically activated [M1]) polarization of macrophages for up to 3 wk post-TBI. Monocytes purified from the injured brain stimulated the proliferation of naive T lymphocytes, enhanced the polarization of T effector cells (TH1/TH17), and decreased the production of regulatory T cells in an MLR. Similarly, elevated T effector cell polarization within blood and brain tis...
Neurosurgery, 2015
Carolina at Chapel Hill. We have developed several simulators for neurosurgical procedures, inclu... more Carolina at Chapel Hill. We have developed several simulators for neurosurgical procedures, including third ventriculocisternostomy, Chiari decompression, minimally invasive spine surgery, etc. These simulators are open-source, cost less than 20toconstruct,andcostlessthan20 to construct, and cost less than 20toconstruct,andcostlessthan0.10 per simulation run. Neurosurgical residents use these surgical simulators to learn key components of neurosurgical procedures. Each simulation run is timed, and every fifth simulation is recorded to assess technical proficiency, adequacy of completion, and other subjective factors. RESULTS: We have demonstrated significant improvements in resident speed, technical proficiency, and adequacy of completion across all simulator platforms. Residents have expressed improved satisfaction with the educational experience as well as improved confidence in the operating room after repeated simulation runs in the lab. CONCLUSION: Surgical skill simulation is an emerging technology and is useful for safe, effective resident training. However, much work in this field has focused on complex, expensive training models. Here, we demonstrate that surgical simulation can be simple, cheap, and provide realistic haptic feedback, and that residents improve both subjectively and objectively with our simulation platforms.
Indian Journal of Research in Homoeopathy, 2015
This paper presents a Content-Based Image Retrieval (CBIR) System called DEICBIR-2. The system re... more This paper presents a Content-Based Image Retrieval (CBIR) System called DEICBIR-2. The system retrieves images similar to a given query image by searching in the provided image database.Standard MPEG-7 image descriptors are used to find the relevant images which are similar to thegiven query image. Direct use of the MPEG-7 descriptors for creating the image database and retrieval on the basis of nearest neighbor does not yield accurate retrievals. To further improve the retrieval results, B-splines are used for ensuring smooth and continuous edges of the images in the edge-based descriptors. Relevance feedback is also implemented with user intervention. These additional features improve the retrieval performance of DEICBIR-2 significantly. Computational performance on a set of query images is presented and the performance of the proposed system is much superior to the performance of DEICBIR[9] on the same database and on the same set of query images.
The rat pheochromocytoma (PC12) cell line is widely applied as a model system to study a variety ... more The rat pheochromocytoma (PC12) cell line is widely applied as a model system to study a variety of neuronal functions. Upon addition of nerve growth factor (NGF), these cells undergo differentiation characterized by an increase in acetylcholinesterase (AChE) activity, and extension of neurite-like processes. Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders and the purpose of this study was to evaluate the effect of Bellis perennis (Be) and Hypericum perforatum (Hy) (6C and 30C) on healthy neuronal cells. Both homeopathic medicines have been studied at three different concentrations of 2 µl/ml, 4 µl/ml and 8 µl/ml for 96 h in PC12 cells differentiated with NGF. The cell viability was tested by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and NRU (Neutral Red Uptake). To observe the oxidative damage and evaluate the antioxidative status after exposure to homeopathic medicines, the level of thiobarbituric acid reactive species (T...
Translational Stroke Research, 2014
We previously reported that remote limb ischemic conditioning (RLIC; PERconditioning) during acut... more We previously reported that remote limb ischemic conditioning (RLIC; PERconditioning) during acute stroke confers neuroprotection, possibly due to increased cerebral blood flow (CBF). Vascular cognitive impairment (VCI) is a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is regarded as the most valid model for VCI. We hypothesized that RLIC (postconditioning; RIPostC) will augment CBF during chronic cerebral hypoperfusion (CCH) and prevent cognitive impairment in the BCAS model. BCAS using customized microcoil was performed in C57/B6 male mice to establish CCH. A week after the BCAS surgery, mice were treated with RIPostC-therapy once daily for 2 weeks. CBF was measured with laser speckle contrast imager at different time points. Cognitive testing was performed at 4-week post-BCAS, and brain tissue was harvested for biochemistry. BCAS led to chronic hypoperfusion resulting into impaired cognitive function as tested by novel object recognition (NOR). Histological examinations revealed that BCAS triggered inflammatory responses and caused frequent vacuolization and cell death. BCAS also increased the generation and accumulation of amyloid beta protein (Aβ), resulting into the loss of white matter (WM) and myelin basic protein (MBP). RIPostC-therapy showed both acute increase as well as sustained improvement in CBF even after the cessation of therapy for a week. RIPostC improved cognitive function, inhibited inflammatory responses, prevented the cell death, reduced the generation and accumulation of Aβ, and protected WM integrity. RIPostC is effective in the BCAS model and could be an attractive low-cost conventional MBK and MNH equally share first author contribution.
Neurological Sciences, 2012
Centella asiatica has been used as psychoactive and antioxidant herbal medicine since ancient tim... more Centella asiatica has been used as psychoactive and antioxidant herbal medicine since ancient time. The present study was design to evaluate the preventive role of ethanolic extract of C. asiatica in middle cerebral artery occlusion (MCAO) in rats. Male Wistar rats were gavaged orally with C. asiatica extract (100, 200 and 300 mg/kg body weight once daily) for 21 days and thereafter subjected to right MCAO for 2 h followed by 22-h reperfusion. Brain injury was evaluated by 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining. Behavioural outcomes as neurological deficit, rota rod test, and grip strength were assessed. In addition, lipid peroxidation, enzymatic and non enzymatic antioxidants were analyzed to assess the oxidative stress. Our results revealed that C. asiatica administration greatly improved neurobehavioral activity and diminished infarction volume along with the restored histological morphology of brain in MCAO rats. Furthermore, supplementation with this extract to MCAO group has reduced the level of thiobarbituric acid reactive species, restored glutathione content and augmented the activities of antioxidant enzymes-catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and superoxide dismutase in a dose-dependent manner in ischemic rats. The remarkable antioxidant activity of C. asiatica may be attributed to its bioactive triterpenes, asiatic acid, asiaticoside, madecassic acid and madecosside and may be translated to clinical level for prevention of ischemic stroke.
Neurochemistry International, 2012
Oxidative stress is involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive im... more Oxidative stress is involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) as well as age related cognitive deficit. The present study was designed to investigate the pre-treatment effects of naringenin (NAR), a polyphenolic compound on cognitive dysfunction, oxidative stress in the hippocampus, and hippocampal neuron injury in a rat model of AD-TNDCI. The rats were pre-treated with NAR at a selective dose (50 mg/kg, orally) for 2 weeks followed by intracerebroventricular-streptozotocin (ICV-STZ) (3 mg/kg; 5 ll per site) injection bilaterally. Behavioral alterations were monitored after 2 weeks from the lesion using passive avoidance test and Morris water maze paradigm. Three weeks after the lesion, the rats were sacrificed for measuring non-enzymatic [4-hydroxynonenal (4-HNE), malonaldehyde (MDA), thiobarbituric reactive substances (TBARS), hydrogen peroxide (H 2 O 2), protein carbonyl (PC), reduced glutathione (GSH)] content and enzymatic [glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and Na + /K +-ATPase] activity in the hippocampus, and expression of choline acetyltransferase (ChAT) positive neuron, and histopathology of hippocampal neurons. The non-enzymatic level and enzymatic activity was significantly increased and decreased, respectively, with striking impairments in spatial learning and memory, loss of ChAT positive neuron and severe damage to hippocampal neurons in the rat induced by ICV-STZ. These abnormalities were significantly improved by NAR pre-treatment. The study suggests that NAR can protect against cognitive deficits, neuronal injury and oxidative stress induced by ICV-STZ, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD-TNDCI.
Therapeutic Applications of Honey and its Phytochemicals, 2020
Honey is one of the most nutritional natural products that not only provides us healthy nutrition... more Honey is one of the most nutritional natural products that not only provides us healthy nutrition but also has a potential to be an alternative treatment option for different pathologies from microbial infection to metabolic disease. Honey is a byproduct of flower syrup produced by honeybees and possesses an intricate chemical composition that varies with botanical sources and geographical locations. This chapter is aimed to provide readers an understanding of complex composition, biological activities, adverse effect, and therapeutic benefits of honey. Honey possesses many biological activities, such as antioxidant, anti-microbial, anti-inflammatory, anti-proliferative, anti-cancer, and anti-metastatic effects, suggesting potential therapeutic roles in many human pathologies. Flavonoids and polyphenols in honey are the two active ingredients, which are of therapeutic importance in many diseases. In conclusion, honey may be developed as a natural therapeutic agent for many pathologies, and extensive studies are therefore recommended.
Journal of Cannabis Research, 2021
Background Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome who... more Background Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experim...
Biomedicines, 2020
Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for... more Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative stress, and inflammatory cascades which lead to chronic pathology. Little can be done to treat the mechanical damage that occurs during the primary insult of a TBI; however, secondary injury mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, oxidative stress, and cell death, can be targeted by therapeutic interventions. Elucidating the many mechanisms underlying secondary injury and studying targets of neuroprotective therapeutic agents is critical for developing new treatments. Therefore, we present a review on the molecular events following TBI from inflammation to programmed cell death and discuss current research and the lates...
Journal of Biochemical and Molecular Toxicology, 2020
Pesticides are globally used to eliminate pests from crops and plants. The increased use of pesti... more Pesticides are globally used to eliminate pests from crops and plants. The increased use of pesticides has posed a serious threat to human health. This study evaluates the effects of pesticide exposure on pregnancy outcomes in tea garden workers (TGW). The acetylcholinesterase (AChE) activity was measured in the maternal blood, placenta, and cord blood of TGW and housewives (HWs). The placental structure and expression of hypoxia‐inducible factor (HIF)‐1α were also analyzed in TGW and HW groups delivering low birth weight (LBW) and normal birth weight (NBW) babies. A significantly decreased AChE activity was observed in maternal blood and cord blood in TGW as compared with HW in the LBW group. However, it did not change significantly in the NBW group (p < .05). The adjusted regression analysis of birth outcomes (birth weight, head circumference, infant's length, and ponderal index) revealed a significant and positive association with the levels of AChE activity in maternal blood, placenta, and cord blood in TGW (p < .05). The histological analysis showed significantly higher placental syncytial knots, chorangiosis, fibrinoid deposition, necrosis, and stromal fibrosis in the LBW group of TGW. Microinfarction, increased fibrinoid deposition, and atypical villi characteristics, such as mushroom‐like structures, were observed during scanning electron microscopy along with increased HIF‐1α expression in placental tissues of TGW exposed to pesticides. Results suggest that occupational pesticide exposure during pregnancy may decrease AChE activity and cause in utero pathological changes accompanied by an increased HIF‐1α expression, which also contributes to placental insufficiency and fetal growth restriction.
Stroke, 2019
Background and Purpose: There is presently no specific therapy for the treatment of VCID. We repo... more Background and Purpose: There is presently no specific therapy for the treatment of VCID. We reported that daily C-RIC (4mo) is effective in young mice by improving cerebral blood flow (CBF), minimizing white matter (WM) damage and improving functional outcomes in Bilateral Carotid Artery Stenosis model (BCAS.) The purpose of this study was to evaluate whether 4 months (4 MO-C-RIC) is effective in male and female aged mouse and if the treatment effects are durable out to 6MOS. Methods: Microcoil induced BCAS model was used to induce chronic hypoperfusion. Adult C57BL/6 both male & female mice (14-months ) were randomly assigned to 3-different groups (N=10), and subjected to Sham, BCAS+sham RIC, BCAS+RIC. C-RIC was started 7d post-surgery daily for 4MOs. Behavioral test and CBF was performed at 1, 4 and 6MO after BCAS and Sham surgery. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for mo...
Traumatic brain injury (TBI) is a major source of worldwide morbidity and mortality. Patients suf... more Traumatic brain injury (TBI) is a major source of worldwide morbidity and mortality. Patients suffering from TBI exhibit a higher susceptibility to bone loss and an increased rate of bone fractures; however, the underlying mechanisms remain poorly defined. Herein, we observed significantly lower bone quality and elevated levels of inflammation in bone and bone marrow niche after controlled cortical impact-induced TBI in in-vivo CD-1 mice. Further, we identified dysregulated NFB signaling, an established mediator of osteoclast differentiation and bone loss, within the bone marrow niche of TBI mice. Ex vivo studies revealed increased osteoclast differentiation in bone marrow-derived cells from TBI mice, as compared to sham injured mice. Finally, we found bone marrow derived extracellular vesicles (EVs) from TBI mice enhanced the colony forming ability and osteoclast differentiation efficacy of bone marrow cells and activated NFB signaling genes in bone marrow-derived cells. Taken to...
The Journal of experimental medicine, Jan 6, 2018
Spontaneous intracerebral hemorrhage (ICH) produces the highest acute mortality and worst outcome... more Spontaneous intracerebral hemorrhage (ICH) produces the highest acute mortality and worst outcomes of all stroke subtypes. Hematoma volume is an independent determinant of ICH patient outcomes, making clot resolution a primary goal of clinical management. Herein, remote-limb ischemic post-conditioning (RIC), the repetitive inflation-deflation of a blood pressure cuff on a limb, accelerated hematoma resolution and improved neurological outcomes after ICH in mice. Parabiosis studies revealed RIC accelerated clot resolution via a humoral-mediated mechanism. Whereas RIC increased anti-inflammatory macrophage activation, myeloid cell depletion eliminated the beneficial effects of RIC after ICH. Myeloid-specific inactivation of the metabolic regulator, AMPKα1, attenuated RIC-induced anti-inflammatory macrophage polarization and delayed hematoma resolution, providing a molecular link between RIC and immune activation. Finally, chimera studies implicated myeloid CD36 expression in RIC-media...
American journal of physiology. Renal physiology, Jan 13, 2018
Hallmark features of acute kidney injury (AKI) include mobilization of immune and inflammatory me... more Hallmark features of acute kidney injury (AKI) include mobilization of immune and inflammatory mechanisms culminating in tissue injury. Emerging information indicates heterogeneity of neutrophils with pro- and anti-inflammatory functions (N1 and N2, respectively). Also, regulatory T-17 (Treg17) cells curtail Th-17-mediated pro-inflammatory responses. However, the status of Treg17 cells and neutrophil phenotypes in AKI are not established. Further, cannabidiol exerts immunoregulatory effects but its impact on Treg17 cells and neutrophil subtypes is not established. Thus, we examined the status of Treg17 cells and neutrophil subtypes in AKI and determined whether cannabidiol favors regulatory neutrophils and T cells accompanied with renoprotection. Accordingly, mice were subjected to bilateral renal ischemia-reperfusion injury (IRI), without or with cannabidiol treatment; thereafter, kidneys were processed for flow cytometry analyses. Renal IRI increased N1 and Th-17 but reduced N2 an...
Translational stroke research, Oct 28, 2017
Over 700 drugs have failed in stroke clinical trials, an unprecedented rate thought to be attribu... more Over 700 drugs have failed in stroke clinical trials, an unprecedented rate thought to be attributed in part to limited and isolated testing often solely in "young" rodent models and focusing on a single secondary injury mechanism. Here, extracellular vesicles (EVs), nanometer-sized cell signaling particles, were tested in a mouse thromboembolic (TE) stroke model. Neural stem cell (NSC) and mesenchymal stem cell (MSC) EVs derived from the same pluripotent stem cell (PSC) line were evaluated for changes in infarct volume as well as sensorimotor function. NSC EVs improved cellular, tissue, and functional outcomes in middle-aged rodents, whereas MSC EVs were less effective. Acute differences in lesion volume following NSC EV treatment were corroborated by MRI in 18-month-old aged rodents. NSC EV treatment has a positive effect on motor function in the aged rodent as indicated by beam walk, instances of foot faults, and strength evaluated by hanging wire test. Increased time w...
Biochimica et biophysica acta, Oct 19, 2017
Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. D... more Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI. In this review, we explore the burgeoning evidence implicating the acute release of damage associated molecular patterns (DAMPs), such as adenosine 5'-triphosphate (ATP), high mobility group box protein 1 (HMGB1), S100 proteins, and hyaluronic acid in the initiation of progressive neurological injury, including white matter loss after TBI. The role that pattern recognition receptors...
Journal of immunology (Baltimore, Md. : 1950), May 24, 2017
Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortal... more Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortality and poor long-term outcomes. Increasing evidence suggests an important, yet poorly defined, role for the immune system in the development of secondary neurologic injury over the days and weeks following a TBI. In this study, we tested the hypothesis that peripheral macrophage infiltration initiates long-lasting adaptive immune responses after TBI. Using a murine controlled cortical impact model, we used adoptive transfer, transgenic, and bone marrow chimera approaches to show increased infiltration and proinflammatory (classically activated [M1]) polarization of macrophages for up to 3 wk post-TBI. Monocytes purified from the injured brain stimulated the proliferation of naive T lymphocytes, enhanced the polarization of T effector cells (TH1/TH17), and decreased the production of regulatory T cells in an MLR. Similarly, elevated T effector cell polarization within blood and brain tis...
Neurosurgery, 2015
Carolina at Chapel Hill. We have developed several simulators for neurosurgical procedures, inclu... more Carolina at Chapel Hill. We have developed several simulators for neurosurgical procedures, including third ventriculocisternostomy, Chiari decompression, minimally invasive spine surgery, etc. These simulators are open-source, cost less than 20toconstruct,andcostlessthan20 to construct, and cost less than 20toconstruct,andcostlessthan0.10 per simulation run. Neurosurgical residents use these surgical simulators to learn key components of neurosurgical procedures. Each simulation run is timed, and every fifth simulation is recorded to assess technical proficiency, adequacy of completion, and other subjective factors. RESULTS: We have demonstrated significant improvements in resident speed, technical proficiency, and adequacy of completion across all simulator platforms. Residents have expressed improved satisfaction with the educational experience as well as improved confidence in the operating room after repeated simulation runs in the lab. CONCLUSION: Surgical skill simulation is an emerging technology and is useful for safe, effective resident training. However, much work in this field has focused on complex, expensive training models. Here, we demonstrate that surgical simulation can be simple, cheap, and provide realistic haptic feedback, and that residents improve both subjectively and objectively with our simulation platforms.
Indian Journal of Research in Homoeopathy, 2015
This paper presents a Content-Based Image Retrieval (CBIR) System called DEICBIR-2. The system re... more This paper presents a Content-Based Image Retrieval (CBIR) System called DEICBIR-2. The system retrieves images similar to a given query image by searching in the provided image database.Standard MPEG-7 image descriptors are used to find the relevant images which are similar to thegiven query image. Direct use of the MPEG-7 descriptors for creating the image database and retrieval on the basis of nearest neighbor does not yield accurate retrievals. To further improve the retrieval results, B-splines are used for ensuring smooth and continuous edges of the images in the edge-based descriptors. Relevance feedback is also implemented with user intervention. These additional features improve the retrieval performance of DEICBIR-2 significantly. Computational performance on a set of query images is presented and the performance of the proposed system is much superior to the performance of DEICBIR[9] on the same database and on the same set of query images.
The rat pheochromocytoma (PC12) cell line is widely applied as a model system to study a variety ... more The rat pheochromocytoma (PC12) cell line is widely applied as a model system to study a variety of neuronal functions. Upon addition of nerve growth factor (NGF), these cells undergo differentiation characterized by an increase in acetylcholinesterase (AChE) activity, and extension of neurite-like processes. Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders and the purpose of this study was to evaluate the effect of Bellis perennis (Be) and Hypericum perforatum (Hy) (6C and 30C) on healthy neuronal cells. Both homeopathic medicines have been studied at three different concentrations of 2 µl/ml, 4 µl/ml and 8 µl/ml for 96 h in PC12 cells differentiated with NGF. The cell viability was tested by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and NRU (Neutral Red Uptake). To observe the oxidative damage and evaluate the antioxidative status after exposure to homeopathic medicines, the level of thiobarbituric acid reactive species (T...
Translational Stroke Research, 2014
We previously reported that remote limb ischemic conditioning (RLIC; PERconditioning) during acut... more We previously reported that remote limb ischemic conditioning (RLIC; PERconditioning) during acute stroke confers neuroprotection, possibly due to increased cerebral blood flow (CBF). Vascular cognitive impairment (VCI) is a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is regarded as the most valid model for VCI. We hypothesized that RLIC (postconditioning; RIPostC) will augment CBF during chronic cerebral hypoperfusion (CCH) and prevent cognitive impairment in the BCAS model. BCAS using customized microcoil was performed in C57/B6 male mice to establish CCH. A week after the BCAS surgery, mice were treated with RIPostC-therapy once daily for 2 weeks. CBF was measured with laser speckle contrast imager at different time points. Cognitive testing was performed at 4-week post-BCAS, and brain tissue was harvested for biochemistry. BCAS led to chronic hypoperfusion resulting into impaired cognitive function as tested by novel object recognition (NOR). Histological examinations revealed that BCAS triggered inflammatory responses and caused frequent vacuolization and cell death. BCAS also increased the generation and accumulation of amyloid beta protein (Aβ), resulting into the loss of white matter (WM) and myelin basic protein (MBP). RIPostC-therapy showed both acute increase as well as sustained improvement in CBF even after the cessation of therapy for a week. RIPostC improved cognitive function, inhibited inflammatory responses, prevented the cell death, reduced the generation and accumulation of Aβ, and protected WM integrity. RIPostC is effective in the BCAS model and could be an attractive low-cost conventional MBK and MNH equally share first author contribution.
Neurological Sciences, 2012
Centella asiatica has been used as psychoactive and antioxidant herbal medicine since ancient tim... more Centella asiatica has been used as psychoactive and antioxidant herbal medicine since ancient time. The present study was design to evaluate the preventive role of ethanolic extract of C. asiatica in middle cerebral artery occlusion (MCAO) in rats. Male Wistar rats were gavaged orally with C. asiatica extract (100, 200 and 300 mg/kg body weight once daily) for 21 days and thereafter subjected to right MCAO for 2 h followed by 22-h reperfusion. Brain injury was evaluated by 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining. Behavioural outcomes as neurological deficit, rota rod test, and grip strength were assessed. In addition, lipid peroxidation, enzymatic and non enzymatic antioxidants were analyzed to assess the oxidative stress. Our results revealed that C. asiatica administration greatly improved neurobehavioral activity and diminished infarction volume along with the restored histological morphology of brain in MCAO rats. Furthermore, supplementation with this extract to MCAO group has reduced the level of thiobarbituric acid reactive species, restored glutathione content and augmented the activities of antioxidant enzymes-catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and superoxide dismutase in a dose-dependent manner in ischemic rats. The remarkable antioxidant activity of C. asiatica may be attributed to its bioactive triterpenes, asiatic acid, asiaticoside, madecassic acid and madecosside and may be translated to clinical level for prevention of ischemic stroke.
Neurochemistry International, 2012
Oxidative stress is involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive im... more Oxidative stress is involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) as well as age related cognitive deficit. The present study was designed to investigate the pre-treatment effects of naringenin (NAR), a polyphenolic compound on cognitive dysfunction, oxidative stress in the hippocampus, and hippocampal neuron injury in a rat model of AD-TNDCI. The rats were pre-treated with NAR at a selective dose (50 mg/kg, orally) for 2 weeks followed by intracerebroventricular-streptozotocin (ICV-STZ) (3 mg/kg; 5 ll per site) injection bilaterally. Behavioral alterations were monitored after 2 weeks from the lesion using passive avoidance test and Morris water maze paradigm. Three weeks after the lesion, the rats were sacrificed for measuring non-enzymatic [4-hydroxynonenal (4-HNE), malonaldehyde (MDA), thiobarbituric reactive substances (TBARS), hydrogen peroxide (H 2 O 2), protein carbonyl (PC), reduced glutathione (GSH)] content and enzymatic [glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and Na + /K +-ATPase] activity in the hippocampus, and expression of choline acetyltransferase (ChAT) positive neuron, and histopathology of hippocampal neurons. The non-enzymatic level and enzymatic activity was significantly increased and decreased, respectively, with striking impairments in spatial learning and memory, loss of ChAT positive neuron and severe damage to hippocampal neurons in the rat induced by ICV-STZ. These abnormalities were significantly improved by NAR pre-treatment. The study suggests that NAR can protect against cognitive deficits, neuronal injury and oxidative stress induced by ICV-STZ, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD-TNDCI.