Browsing by Author "Hari S. Sharma"

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Development of in vivo drug-induced neurotoxicity models
(Informa Healthcare, 2014) Hari S. Sharma; Preeti Menon; José Vicente Lafuente; Dafin F. Muresanu; Z Ryan Tian; Ranjana Patnaik; Aruna Sharma
Introduction: Neurotoxicity caused by diverse psychostimulant drugs, for example, methamphetamine, 3,4-methylenedioxy-methamphetamine, cocaine or morphine is a cause of concern to human populations especially the young generation across the world. These recreational drugs affect brain function severely leading to addiction and brain pathology. Use of psychostimulants may induce breakdown of the blood-brain barrier to serum proteins resulting in adverse brain microenvironment, edema cell injury or eventually neuronal death. Thus, there is an urgent need to find out detailed mechanisms of psychostimulants-induced neurotoxicity in vivo models for suitable therapeutic strategies to induce neuroprotection and also to help de-addiction in clinical situations.Areas covered: In this review, psychostimulants drugs-induced neurotoxicity is discussed in view of recent literature and the financial burden it may pose on our society due to rehabilitation and de-addiction. Furthermore, experimental evidences of drug-induced neuroprotection are also discussed.Expert opinion: Use of in vivo models of neurotoxicity caused by psychostimulants is discussed based on author's own research and to find suitable drugs that could induce neuroprotection including nanodelivery. Furthermore, novel therapeutic agents for de-addiction and reducing neurotoxicity following psychostimulants administration are presented. © 2014 Informa UK, Ltd.
Exacerbation of brain pathology after partial restraint in hypertensive rats following SiO2 nanoparticles exposure at high ambient temperature
(Humana Press Inc., 2013) Hari S. Sharma; Dafin F. Muresanu; Ranjana Patnaik; Aruna Sharma
This investigation examines the possibility that exposure to silica dust of hypertensive individuals may exacerbate brain pathology and sensory motor dysfunction at high environmental temperature. Hypertension was produced in rats (200-250 g) by two-kidney one clip (2K1C) method, and in these animals, SiO2 nanoparticles (NPs; 50 to 60 nm) were administered at 50 mg/kg, i.p. daily for 1 week. On the 8th day, these rats were subjected to partial restraint in a Perspex box for 4 h either at room temperature (21 C) or at 33 C in a biological oxygen demand incubator (wind velocity, 2.6 cm/s; relative humidity, 65 to 67 %). In these animals, behavioral functions, blood-brain barrier (BBB) permeability to Evans blue albumin (EBA) and radioiodine ( [131]-Iodine), brain water content and neuronal injuries were determined. Hypertensive rats subjected to 4 h restraint at room temperature did not exhibit BBB dysfunction, brain edema, neural injury, or alterations in rotarod or inclined plane angle performances. However, when these hypertensive rats were subjected to restraint at 33 C, breakdown of the cortical BBB (EBA, +38 %; radioiodine, +56 %), brain water (+0.88 %), neuronal damages (+18 %), and behavioral impairment were exacerbated. Interestingly, SiO2 exposure to these rats further exacerbated BBB breakdown (EBA, 280 %; radioiodine, 350 %), brain edema (4 %), and neural injury (30 %) after identical restraint depending on the ambient temperature. SiO2 treatment also induced brain pathology and alteration in behavioral functions in normotensive rats after restraint at high temperature. These observations clearly show that hypertension significantly enhances restraint-induced brain pathology, and behavioral anomalies particularly at high ambient temperature and SiO 2 intoxication further exacerbated these brain pathologies and cognitive dysfunctions. © 2013 Springer Science+Business Media New York.
Intracerebral administration of neuronal nitric oxide synthase antiserum attenuates traumatic brain injury-induced blood-brain barrier permeability, brain edema formation, and sensory motor disturbances in the rat
(Springer-Verlag Wien, 2006) Hari S. Sharma; L. Wiklund; R.D. Badgaiyan; S. Mohanty; P. Alm
The role of nitric oxide (NO) in traumatic brain injury (TBI)-induced sensory motor function and brain pathology was examined using intracerebral administration of neuronal nitric oxide synthase (nNOS) antiserum in a rat model. TBI was produced by a making a longitudinal incision into the right parietal cerebral cortex limited to the dorsal surface of the hippocampus. Focal TBI induces profound edematous swelling, extravasation of Evans blue dye, and up-regulation of nNOS in the injured cerebral cortex and the underlying subcortical areas at 5 hours. The traumatized animals exhibited pronounced sensory motor deficit, as seen using Rota-Rod and grid-walking tests. Intracerebral administration of nNOS antiserum (1 : 20) 5 minutes and 1 hour after TBI significantly attenuated brain edema formation, Evans blue leakage, and nNOS expression in the injured cortex and the underlying subcortical regions. The nNOS antiserum-treated rats showed improved sensory motor functions. However, administration of nNOS antiserum 2 hours after TBI did not influence these parameters significantly. These novel observations suggest that NO participates in blood-brain barrier disruption, edema formation, and sensory motor disturbances in the early phase of TBI, and that nNOS antiserum has some potential therapeutic value requiring additional investigation. © 2006 Springer-Verlag.
Nanowired delivery of mesenchymal stem cell reduces diabetes induced aggravation brain damage following heatstroke
(Nano Science and Technology Institute, 2014) Hari S. Sharma; Lianyuan Feng; José Vicente Lafuente; Dafin F. Muresanu; Z. Ryan Tian; Ranjana Patnaik; Aruna Sharma
Our military personnel are often exposed to combat operations in hot environments in summer months (40 to 42°C) that often lead to heatstroke. Since endocrine disorders e.g., diabetes could result from posttraumatic stress disorders (PTSD) in military populations; these soldiers are highly vulnerable to additional heat stress. Previous reports from our lab suggest that diabetic rats showed greater brain pathology after heat stress. This suggests that military personnel with diabetes in heat stress have higher brain pathology during combat stress or other activities. Since stem cells are known to induce neuroprotection we examined whether nanodelivery of mesenchymal stem cells (MSCs) could enhance the potential neuroprotective effects of stem cells and reduce the aggravation of brain pathology in heat stress in diabetic rat model. Our observations clearly show that nanodelivery of MSCs markedly attenuated heat stress induced brain pathology in diabetic rats.
Retraction note: Cardiac Arrest Alters Regional Ubiquitin Levels in Association with the Blood–Brain Barrier Breakdown and Neuronal Damages in the Porcine Brain (Molecular Neurobiology, (2015), 52, 2, (1043-1053), 10.1007/s12035-015-9254-7)
(Springer, 2024) Hari S. Sharma; Ranjana Patnaik; Aruna Sharma; José Vicente Lafuente; Adriana Miclescu; Lars Wiklund
The Editor-in-Chief has retracted this article because of concerns regarding the figures presented in this work. These concerns call into question the article's overall scientific soundness. An investigation conducted after its publication discovered the following issues: The right half of the ROSC 120 min. Panel in Figure 1, when re-scaled, appears to overlap with the left half of the MB + ROSC 120 min. Panel in the same figure. These Panels represent tissues taken from animals subject to different experimental conditions; The right half of the MB + ROSC 120 min. Panel of Figure 1, when re-scaled, appears to overlap with the left half of the MB + ROSC 180 min. Panel in the same figure. These Panels represent tissues taken from animals subject to different experimental conditions. The right half of the ROSC 120 min. Panel in Figure 1, when re-scaled, appears to overlap with the left half of the MB + ROSC 120 min. Panel in the same figure. These Panels represent tissues taken from animals subject to different experimental conditions; The right half of the MB + ROSC 120 min. Panel of Figure 1, when re-scaled, appears to overlap with the left half of the MB + ROSC 180 min. Panel in the same figure. These Panels represent tissues taken from animals subject to different experimental conditions. The Editor-in-Chief therefore no longer has confidence in the integrity of the research presented in this article. Hari S. Sharma and Aruna Sharma disagree with this retraction. Ranjana Patnaik, José Vicente Lafuente, Adriana Miclescu, and Lars Wiklund have not replied to correspondence from the Publisher. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
Retraction to: Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron (Molecular Neurobiology, (2015), 52, 2, (867-881), 10.1007/s12035-015-9236-9)
(Springer, 2024) Aruna Sharma; Dafin F. Muresanu; José V. Lafuente; Ranjana Patnaik; Z. Ryan Tian; Anca D. Buzoianu; Hari S. Sharma
The Editor-in-Chief has retracted this article because of concerns regarding figures presented in this work. These concerns call into question the article's overall scientific soundness. An investigation conducted after its publication discovered that a portion of the top right corner of Panel d of Figure 6 appears to overlap with a portion of the bottom half of Panel c of the same figure. These panels represent tissues taken from animals subject to different experimental conditions. The Editor-in-Chief therefore no longer has confidence in the integrity of the research presented in this article. Hari Shanker Sharma and Aruna Sharma disagree with this retraction. Anca D. Buzoianu agrees with this retraction. Dafin F. Muresanu, José V. Lafuente, Ranjana Patnaik, and Z. Ryan Tian have not replied to correspondence from the Publisher. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
Size- and age-dependent neurotoxicity of engineered metal nanoparticles in rats
(Humana Press Inc., 2013) Aruna Sharma; Dafin F. Muresanu; Ranjana Patnaik; Hari S. Sharma
Earlier we showed that chronic administration of engineered nanoparticles (NPs) from metals, e.g., Cu, Ag, or Al (50-60 nm, 50 mg/kg, i.p. daily for 1 week) alter blood-brain barrier (BBB) disruption and induce brain pathology in adult rats (age 18 to 22 weeks). However, effects of size-dependent neurotoxicity of NPs in vivo are still largely unknown. In present investigation, we examined the effects of different size ranges of the above-engineered NPs on brain pathology in rats. Furthermore, the fact that age is also an important factor in brain pathology was also investigated in our rat model. Our results showed that small-sized NPs induced the most pronounced BBB breakdown (EBA +480 to 680 %; radioiodine +850 to 1025 %), brain edema formation (+4 to 6 %) and neuronal injuries (+30 to 40 %), glial fibrillary acidic protein upregulation (+40 to 56 % increase), and myelin vesiculation (+30 to 35 % damage) in young animals as compared to controls. Interestingly, the oldest animals (30 to 35 weeks of age) also showed massive brain pathology as compared to young adults (18 to 20 weeks old). The Ag and Cu exhibited greater brain damage compared with Al NPs in all age groups regardless of their size. This suggests that apart from the size, the composition of NPs is also important in neurotoxicity. The very young and elderly age groups exhibited greater neurotoxicity to NPs suggests that children and elderly are more vulnerable to NPs-induced brain damage. The NPs-induced brain damage correlated well with the upregulation of neuronal nitric oxide synthase activity in the brain indicating that NPs-induced neurotoxicity may be mediated via increased production of nitric oxide, not reported earlier. © 2013 Springer Science+Business Media New York.
Ti02 Nanowired Cerebrolysin enhances neuroprotective effects of mesenchymal stem cells following concussive head injury at hot environments
(Taylor and Francis Inc., 2015) Hari S. Sharma; Dafin F. Muresanu; Lianyuan Feng; Jose Vicente Lafuente; Ranjana Patnaik; Z Ryan Tian; Asya Ozikzilcik; Herbert Mossier; Aruna Sharma
Military personnel are often working in hot environment where concussive head injury (CHI) during combat operations is quite common. In this innovation we for the first time show that traumatic brain injury occurring in hot environment is exacerbated and this could be due to lack of neurotrophic factors. Thus, nanowired delivery of Cerebrolsyin, a balanced composition of several neurotrophic factors and active peptide fragments could be useful for reducing the brain pathology either alone or together with mesenchymal stem cells (MSCs) in CHI during hot environments. Our observations show that Ti02 nanowired delivered Cerebrolsyin potentiates MSCs induced neurorepair and neuroregeration. This research has potential clinical significance for our armed forces that are working hard in hot environment during combat operations. Copyright 2015 by TechConnect. All rights reserved.