Browsing by Author "Aruna Sharma"

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5-Hydroxytryptophan: A precursor of serotonin influences regional blood-brain barrier breakdown, cerebral blood flow, brain edema formation, and neuropathology
(Academic Press Inc., 2019) Aruna Sharma; Rudy J. Castellani; Mark A. Smith; Dafin Fior Muresanu; Prasanta Kumar Dey; Hari Shanker Sharma
5-Hydroxytryptophan (5-HTP), a precursor of serotonin, is therapeutically used for several psychiatric disorders such as anxiety and depression in the clinic. However, severe side effects, including abnormal mental functions, behavioral disturbances and intolerance are associated with this treatment. 5-HTP-induced elevation of plasma and brain serotonin levels may affect blood-brain barrier (BBB) breakdown, edema formation and regional cerebral blood flow (CBF) disturbances. Breakdown of BBB to serum proteins leads to vasogenic brain edema formation and cellular injuries. However, 5-HTP-neurotoxicity is still not well known. In this investigations 5-HTP induced elevation of endogenous plasma and brain serotonin levels and its effect on BBB breakdown, edema formation neuronal injuries was examined in a rat model. Furthermore, potential role of oxidative stress and nitric oxide (NO) was evaluated. In addition, several neurochemical agents such as p-CPA (5-HT synthesis inhibitor) indomethacin (prostaglandin synthase inhibitor), diazepam (ant stress drug), cyproheptadine, ketanserin (5-HT2 receptor antagonists) and vinblastine (inhibitor of microtubule function) were examined on 5-HT neurotoxicity. Our observations suggest that 4 h after 5-HTP administrations, the endogenous serotonin levels increased by fourfold (150 mg/kg) in the plasma and brain associated with profound hyperthermia (+ 3.86 ± 0.24 °C, oxidative stress and NO upregulation. Breakdown of the BBB to Evans blue albumin (EBA) in 8 brain regions and to [131]Iodine in 14 brain regions was observed. The CBF exhibited marked reduction in all the brain regions examined. Brain edema and cellular injuries are present in the areas associated with BBB disruption. Drug treatments reduced the BBB breakdown, edema formation NO production and brain pathology. These observations are the first to point out that 5-HTP-neurotoxicity caused by BBB breakdown, edema formation and NO production is instrumental in causing adverse mental and behavioral abnormalities, not reported earlier. © 2019 Elsevier Inc.
Alzheimer's disease neuropathology is exacerbated following traumatic brain injury. Neuroprotection by co-administration of nanowired mesenchymal stem cells and cerebrolysin with monoclonal antibodies to amyloid beta peptide
(Elsevier B.V., 2021) Hari Shanker Sharma; Dafin F. Muresanu; Rudy J. Castellani; Ala Nozari; José Vicente Lafuente; Anca D. Buzoianu; Seaab Sahib; Z. Ryan Tian; Igor Bryukhovetskiy; Igor Manzhulo; Preeti K. Menon; Ranjana Patnaik; Lars Wiklund; Aruna Sharma
Military personnel are prone to traumatic brain injury (TBI) that is one of the risk factors in developing Alzheimer's disease (AD) at a later stage. TBI induces breakdown of the blood-brain barrier (BBB) to serum proteins into the brain and leads to extravasation of plasma amyloid beta peptide (ΑβP) into the brain fluid compartments causing AD brain pathology. Thus, there is a need to expand our knowledge on the role of TBI in AD. In addition, exploration of the novel roles of nanomedicine in AD and TBI for neuroprotection is the need of the hour. Since stem cells and neurotrophic factors play important roles in TBI and in AD, it is likely that nanodelivery of these agents exert superior neuroprotection in TBI induced exacerbation of AD brain pathology. In this review, these aspects are examined in details based on our own investigations in the light of current scientific literature in the field. Our observations show that TBI exacerbates AD brain pathology and TiO2 nanowired delivery of mesenchymal stem cells together with cerebrolysin—a balanced composition of several neurotrophic factors and active peptide fragments, and monoclonal antibodies to amyloid beta protein thwarted the development of neuropathology following TBI in AD, not reported earlier. © 2021 Elsevier B.V.
Anesthetics influence concussive head injury induced blood-brain barrier breakdown, brain edema formation, cerebral blood flow, serotonin levels, brain pathology and functional outcome
(Academic Press Inc., 2019) Hari Shanker Sharma; Dafin Fior Muresanu; Ala Nozari; Rudy J. Castellani; Prasanta Kumar Dey; Lars Wiklund; Aruna Sharma
Several lines of evidences show that anesthetics influence neurotoxicity and neuroprotection. The possibility that different anesthetic agents potentially influence the pathophysiological and functional outcome following neurotrauma was examined in a rat model of concussive head injury (CHI). The CHI was produced by an impact of 0.224 N on the right parietal bone by dropping a weight of 114.6 g from a 20 cm height under different anesthetic agents, e.g., inhaled ether anesthesia or intraperitoneally administered ketamine, pentobarbital, equithesin or urethane anesthesia. Five hour CHI resulted in profound volume swelling and brain edema formation in both hemispheres showing disruption of the blood-brain barrier (BBB) to Evans blue and radioiodine. A marked decrease in the cortical CBF and a profound increase in plasma or brain serotonin levels were seen at this time. Neuronal damages were present in several parts of the brain. These pathological changes were most marked in CHI under ether anesthesia followed by ketamine (35 mg/kg, i.p.), pentobarbital (50 mg/kg, i.p.), equithesin (3 mL/kg, i.p.) and urethane (1 g/kg, i.p.). The functional outcome on Rota Rod performances or grid walking tests was also most adversely affected after CHI under ether anesthesia followed by pentobarbital, equithesin and ketamine. Interestingly, the plasma and brain serotonin levels strongly correlated with the development of brain edema in head injured animals in relation to different anesthetic agents used. These observations suggest that anesthetic agents are detrimental to functional and pathological outcomes in CHI probably through influencing the circulating plasma and brain serotonin levels, not reported earlier. Whether anesthetics could also affect the efficacy of different neuroprotective agents in CNS injuries is a new subject that is currently being examined in our laboratory. © 2019 Elsevier Inc.
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.
Histamine H3 and H4 receptors modulate Parkinson's disease induced brain pathology. Neuroprotective effects of nanowired BF-2649 and clobenpropit with anti-histamine-antibody therapy
(Elsevier B.V., 2021) Aruna Sharma; Dafin F. Muresanu; Ranjana Patnaik; Preeti K. Menon; Z. Ryan Tian; Seaab Sahib; Rudy J. Castellani; Ala Nozari; José Vicente Lafuente; Anca D. Buzoianu; Stephen D. Skaper; Igor Bryukhovetskiy; Igor Manzhulo; Lars Wiklund; Hari Shanker Sharma
Military personnel deployed in combat operations are highly prone to develop Parkinson's disease (PD) in later lives. PD largely involves dopaminergic pathways with hallmarks of increased alpha synuclein (ASNC), and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) precipitating brain pathology. However, increased histaminergic nerve fibers in substantia nigra pars Compacta (SNpc), striatum (STr) and caudate putamen (CP) associated with upregulation of Histamine H3 receptors and downregulation of H4 receptors in human cases of PD is observed in postmortem cases. These findings indicate that modulation of histamine H3 and H4 receptors and/or histaminergic transmission may induce neuroprotection in PD induced brain pathology. In this review effects of a potent histaminergic H3 receptor inverse agonist BF-2549 or clobenpropit (CLBPT) partial histamine H4 agonist with H3 receptor antagonist, in association with monoclonal anti-histamine antibodies (AHmAb) in PD brain pathology is discussed based on our own observations. Our investigation shows that chronic administration of conventional or TiO2 nanowired BF 2649 (1 mg/kg, i.p.) or CLBPT (1 mg/kg, i.p.) once daily for 1 week together with nanowired delivery of HAmAb (25 μL) significantly thwarted ASNC and p-tau levels in the SNpC and STr and reduced PD induced brain pathology. These observations are the first to show the involvement of histamine receptors in PD and opens new avenues for the development of novel drug strategies in clinical strategies for PD, not reported earlier. © 2021 Elsevier B.V.
Methamphetamine exacerbates pathophysiology of traumatic brain injury at high altitude. Neuroprotective effects of nanodelivery of a potent antioxidant compound H-290/51
(Elsevier B.V., 2021) Hari Shanker Sharma; José Vicente Lafuente; Lianyuan Feng; Dafin F. Muresanu; Preeti K. Menon; Rudy J. Castellani; Ala Nozari; Seaab Sahib; Z. Ryan Tian; Anca D. Buzoianu; Per-Ove Sjöquist; Ranjana Patnaik; Lars Wiklund; Aruna Sharma
Military personnel are often exposed to high altitude (HA, ca. 4500–5000 m) for combat operations associated with neurological dysfunctions. HA is a severe stressful situation and people frequently use methamphetamine (METH) or other psychostimulants to cope stress. Since military personnel are prone to different kinds of traumatic brain injury (TBI), in this review we discuss possible effects of METH on concussive head injury (CHI) at HA based on our own observations. METH exposure at HA exacerbates pathophysiology of CHI as compared to normobaric laboratory environment comparable to sea level. Increased blood-brain barrier (BBB) breakdown, edema formation and reductions in the cerebral blood flow (CBF) following CHI were exacerbated by METH intoxication at HA. Damage to cerebral microvasculature and expression of beta catenin was also exacerbated following CHI in METH treated group at HA. TiO2-nanowired delivery of H-290/51 (150 mg/kg, i.p.), a potent chain-breaking antioxidant significantly enhanced CBF and reduced BBB breakdown, edema formation, beta catenin expression and brain pathology in METH exposed rats after CHI at HA. These observations are the first to point out that METH exposure in CHI exacerbated brain pathology at HA and this appears to be related with greater production of oxidative stress induced brain pathology, not reported earlier. © 2021 Elsevier B.V.
Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury
(Elsevier B.V., 2021) Feng Niu; Aruna Sharma; Zhenguo Wang; Lianyuan Feng; Dafin F. Muresanu; Seaab Sahib; Z. Ryan Tian; José Vicente Lafuente; Anca D. Buzoianu; Rudy J. Castellani; Ala Nozari; Preeti K. Menon; Ranjana Patnaik; Lars Wiklund; Hari Shanker Sharma
Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims. Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224 N results in profound progressive functional deficit, memory impairment and brain pathology from 5 h after trauma that continued over several weeks of injury. In this investigation we report that TiO2 nanowired delivery of oxiracetam (50 mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100 mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier. © 2021 Elsevier B.V.
Nanodelivery of traditional Chinese Gingko Biloba extract EGb-761 and bilobalide BN-52021 induces superior neuroprotective effects on pathophysiology of heat stroke
(Elsevier B.V., 2021) Seaab Sahib; Aruna Sharma; Dafin F. Muresanu; Zhiqiang Zhang; Cong Li; Z. Ryan Tian; Anca D. Buzoianu; José Vicente Lafuente; Rudy J. Castellani; Ala Nozari; Ranjana Patnaik; Preeti K. Menon; Lars Wiklund; Hari Shanker Sharma
Military personnel often exposed to high summer heat are vulnerable to heat stroke (HS) resulting in abnormal brain function and mental anomalies. There are reasons to believe that leakage of the blood-brain barrier (BBB) due to hyperthermia and development of brain edema could result in brain pathology. Thus, exploration of suitable therapeutic strategies is needed to induce neuroprotection in HS. Extracts of Gingko Biloba (EGb-761) is traditionally used in a variety of mental disorders in Chinese traditional medicine since ages. In this chapter, effects of TiO2 nanowired EGb-761 and BN-52021 delivery to treat brain pathologies in HS is discussed based on our own investigations. We observed that TiO2 nanowired delivery of EGb-761 or TiO2 BN-52021 is able to attenuate more that 80% reduction in the brain pathology in HS as compared to conventional drug delivery. The functional outcome after HS is also significantly improved by nanowired delivery of EGb-761 and BN-52021. These observations are the first to suggest that nanowired delivery of EGb-761 and BN-52021 has superior therapeutic effects in HS not reported earlier. The clinical significance in relation to the military medicine is discussed. © 2021 Elsevier B.V.
Nanodrug delivery by single-walled carbon nanotubes (SWCNTs) in the central nervous system induces neurotoxicity. Potential neuroprotective effects of Cerebrolysin
(Nano Science and Technology Institute, 2014) HariS Sharma; DafinF Muresanu; José Vicente Lafuente; Ranjana Patnaik; Z. Ryan Tian; Herbert Mos̈sler; Aruna Sharma
Our military personnel are often inflicted with brain or spinal cord injury during combat operations caused by gunshot, missile explosions, fall or direct blunt or sharp trauma to their CNS leading to life threatening illnesses. Recently, single-walled carbon nanotubes (SWCNTs) are used for nano drug delivery in cancer therapy however; SWCNTs induced neurotoxicity is not well known. In this innovation, we used Cerebrolsyin, a balanced composition of several neurotrophic factors and active peptide fragments in attenuating SWCNTs induced neurotoxicity in the rat central nervous system (CNS). These observations support the idea that co-administration of Cerebrolsyin with SWCNTs is needed to enhance the neuroprotective effects of nanodrug delivery using SWCNTs as a vehicle.
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.
Neuroprotective effects of insulin like growth factor-1 on engineered metal nanoparticles Ag, Cu and Al induced blood-brain barrier breakdown, edema formation, oxidative stress, upregulation of neuronal nitric oxide synthase and brain pathology
(Elsevier B.V., 2021) Hari Shanker Sharma; José Vicente Lafuente; Dafin F. Muresanu; Seaab Sahib; Z. Ryan Tian; Preeti K. Menon; Rudy J. Castellani; Ala Nozari; Anca D. Buzoianu; Per-Ove Sjöquist; Ranjana Patnaik; Lars Wiklund; Aruna Sharma
Military personnel are vulnerable to environmental or industrial exposure of engineered nanoparticles (NPs) from metals. Long-term exposure of NPs from various sources affect sensory-motor or cognitive brain functions. Thus, a possibility exists that chronic exposure of NPs affect blood-brain barrier (BBB) breakdown and brain pathology by inducing oxidative stress and/or nitric oxide production. This hypothesis was examined in the rat intoxicated with Ag, Cu or Al (50–60 nm) nanoparticles (50 mg/kg, i.p. once daily) for 7 days. In these NPs treated rats the BBB permeability, brain edema, neuronal nitric oxide synthase (nNOS) immunoreactivity and brain oxidants levels, e.g., myeloperoxidase (MP), malondialdehyde (MD) and glutathione (GT) was examined on the 8th day. Cu and Ag but not Al nanoparticles increased the MP and MD levels by twofold in the brain although, GT showed 50% decline. At this time increase in brain water content and BBB breakdown to protein tracers were seen in areas exhibiting nNOS positive neurons and cell injuries. Pretreatment with insulin like growth factor-1 (IGF-1) in high doses (1 μg/kg, i.v. but not 0.5 μg/kg daily for 7 days) together with NPs significantly reduced the oxidative stress, nNOS upregulation, BBB breakdown, edema formation and cell injuries. These novel observations demonstrate that (i) NPs depending on their metal constituent (Cu, Ag but not Al) induce oxidative stress and nNOS expression leading to BBB disruption, brain edema and cell damage, and (ii) IGF-1 depending on doses exerts powerful neuroprotection against nanoneurotoxicity, not reported earlier. © 2021 Elsevier B.V.
Quercetin in Hypoxia-Induced Oxidative Stress: Novel Target for Neuroprotection
(Academic Press Inc., 2012) Anand Kumar Pandey; Ranjana Patnaik; Dafin F. Muresanu; Aruna Sharma; Hari Shanker Sharma
Oxidative stress in the central nervous system is one of the key players for neurodegeneration. Thus, antioxidants could play important roles in treating several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and aging-related brain disorders. This review is focused on the new developments in oxidative stress-induced neurodegeneration. Further, based on our own investigations, new roles of quercetin, an antioxidant compound in hypoxia and ischemia induced neuroprotection in relation to suppression of oxidative stress, improvement in behavioral function, reduction in infarct volume, brain swelling, and cellular injury in both in vivo and in vitro models are discussed. Our new findings clearly suggest that antioxidant compounds have potential role in therapeutic strategies to treat neurodegenerative diseases in clinical settings. © 2012 Elsevier Inc.
Retraction Note to: Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer’s Disease (Molecular Neurobiology, (2018), 55, 1, (300-311), 10.1007/s12035-017-0742-9)
(Springer, 2025) Hari Shanker Sharma; Dafin Fior Mureşanu; José Vicente Lafuente; Ranjana Saksena Patnaik; Zhengrong Ryan Tian; Asya Ozkizilcik; Rudy J. Castellani; Herbert Mössler; Aruna Sharma
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 bottom left corner of Panel c of Fig. 1 appears to overlap with a portion of the top right corner of Panel d of the same figure; The top half of Panel a of Fig. 2 appears to overlap with the bottom half of Panel b of the same figure; The top half of Panel b of Fig. 2 appears to overlap with the bottom half of Panel c of the same Figure; The top half of Panel c of Fig. 2 appears to overlap with the bottom half of Panel f of the same figure. The bottom left corner of Panel c of Fig. 1 appears to overlap with a portion of the top right corner of Panel d of the same figure; The top half of Panel a of Fig. 2 appears to overlap with the bottom half of Panel b of the same figure; The top half of Panel b of Fig. 2 appears to overlap with the bottom half of Panel c of the same Figure; The top half of Panel c of Fig. 2 appears to overlap with the bottom half of Panel f of the same figure. These panels represent different types of tissue or tissues taken from animals which underwent different treatments. 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. Dafin Fior Muresanu, José Vicente Lafuente, Ranjana Patnaik, Z. Ryan Tian, Asya Ozkizilcik, and Herbert Mössler have not replied to correspondence from the Publisher. Rudy J. Castellani, who is listed as a co-author of this article, has stated that he did not participate in the research reported therein and that his name and affiliation were added to the author list without his consent. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
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 Note: 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, 2025) Aruna Sharma; Dafin Fior Mureşanu; José Vicente Lafuente; Ranjana Saksena Patnaik; Zhengrong Ryan Tian; Anca Dana Buzoianu; Hari Shanker 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.
Retraction to: Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer’s Disease (Molecular Neurobiology, (2018), 55, 1, (300-311), 10.1007/s12035-017-0742-9)
(Springer, 2024) Hari Shanker Sharma; Dafin Fior Muresanu; José Vicente Lafuente; Ranjana Patnaik; Z. Ryan Tian; Asya Ozkizilcik; Rudy J. Castellani; Herbert Mössler; Aruna Sharma
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 bottom left corner of Panel c of Fig. 1 appears to overlap with a portion of the top right corner of Panel d of the same figure; The top half of Panel a of Fig. 2 appears to overlap with the bottom half of Panel b of the same figure; The top half of Panel b of Fig. 2 appears to overlap with the bottom half of Panel c of the same Figure; The top half of Panel c of Fig. 2 appears to overlap with the bottom half of Panel f of the same figure. The bottom left corner of Panel c of Fig. 1 appears to overlap with a portion of the top right corner of Panel d of the same figure; The top half of Panel a of Fig. 2 appears to overlap with the bottom half of Panel b of the same figure; The top half of Panel b of Fig. 2 appears to overlap with the bottom half of Panel c of the same Figure; The top half of Panel c of Fig. 2 appears to overlap with the bottom half of Panel f of the same figure. These panels represent different types of tissue or tissues taken from animals which underwent different treatments. 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. Dafin Fior Muresanu, José Vicente Lafuente, Ranjana Patnaik, Z. Ryan Tian, Asya Ozkizilcik, and Herbert Mössler have not replied to correspondence from the Publisher. Rudy J. Castellani, who is listed as a co-author of this article, has stated that he did not participate in the research reported therein and that his name and affiliation were added to the author list without his consent. © 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.
Superior antioxidant and anti-ischemic neuroprotective effects of cerebrolysin in heat stroke following intoxication of engineered metal Ag and Cu nanoparticles: A comparative biochemical and physiological study with other stroke therapies
(Elsevier B.V., 2021) Hari Shanker Sharma; Dafin F. Muresanu; Asya Ozkizilcik; Seaab Sahib; Z. Ryan Tian; José Vicente Lafuente; Rudy J. Castellani; Ala Nozari; Lianyuan Feng; Anca D. Buzoianu; Preeti K. Menon; Ranjana Patnaik; Lars Wiklund; Aruna Sharma
Military personnel are often exposed to high environmental heat associated with industrial or ambient abundance of nanoparticles (NPs) affecting brain function. We have shown that engineered metal NPs Ag and Cu exacerbate hyperthermia induced brain pathology. Thus, exploration of novel drug therapy is needed for effective neuroprotection in heat stroke intoxicated with NPs. In this investigation neuroprotective effects of cerebrolysin, a balanced composition of several neurotrophic factors and active peptides fragments exhibiting powerful antioxidant and anti-ischemic effects was examined in heat stroke after NPs intoxication. In addition, its efficacy is compared to currently used drugs in post-stroke therapies in clinics. Thus, levertiracetam, pregabalin, topiramat and valproate were compared in standard doses with cerebrolysin in heat stroke intoxicated with Cu or Ag NPs (50–60 nm, 50 mg/kg, i.p./day for 7 days). Rats were subjected to 4 h heat stress (HS) in a biological oxygen demand incubator at 38 °C (Relative Humidity 45–47%; Wind velocity 22.4–25.6 cm/s) that resulted in profound increase in oxidants Luminol, Lucigenin, Malondialdehyde and Myeloperoxidase, and a marked decrease in antioxidant Glutathione. At this time severe reductions in the cerebral blood flow (CBF) was seen together with increased blood-brain barrier (BBB) breakdown and brain edema formation. These pathophysiological responses were exacerbated in NPs treated heat-stressed animals. Pretreatment with cerebrolysin (2.5 mL/kg, i.v.) once daily for 3 days significantly attenuated the oxidative stress, BBB breakdown and brain edema and improved CBF in the heat stressed group. The other drugs were least effective on brain pathology following heat stroke. However, in NPs treated heat stressed animals 5 mL/kg conventional cerebrolysin and 2.5 mL/kg nanowired cerebrolysin is needed to attenuate oxidative stress, BBB breakdown, brain edema and to improve CBF. Interestingly, the other drugs even in higher doses used are unable to alter brain pathologies in NPs and heat stress. These observations are the first to demonstrate that cerebrolysin is the most superior antioxidant and anti-ischemic drug in NPs exposed heat stroke, not reported earlier. © 2021 Elsevier B.V.