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| 2. |
- Sharma, Hari Shanker, et al.
(author)
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6th Global College of Neuroprotection and Neuroregeneration, annual meeting
- 2009
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In: Expert review of neurotherapeutics. - : Informa UK Limited. - 1744-8360 .- 1473-7175. ; 9:7, s. 941-947
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Journal article (peer-reviewed)abstract
- The 6th Global College of Neuroprotection and Neuroregeneration (GCNN) and 5th Society for Study on Neuroplasticity and Neuroregeneration (SSNN) conference was held jointly in the Hilton Hotel, Vienna, Austria, 1-4 March 2009. This was the second annual joint conference of the two societies and it was highly successful from a scientific point of view, as it saw a gathering of the top basic and clinical scientists whose research is currently at the cutting edge of neuroscience. This conference saw 86 invited lectures from carefully selected leading scientists from around the world, along with 56 posters of young scientists researching of a focal theme. Over the 3 days, in 32 sessions, new developments in neuroprotection and new ways to enhance neuroregeneration were discussed intensively among more than 600 delegates. In addition, approximately 40 representatives of drug companies, five representatives from scientific publishers and 14 representatives from scientific instruments and supplies-related industries also actively participated in this huge neuroscience event. The GCNN and SSNN conference achieved a new milestone in scientific success in Vienna and established an excellent new working collaboration among the participants in a pleasant, enriched environment with several social gatherings.
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| 3. |
- Sharma, Hari Shanker, et al.
(author)
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Chronic Treatment with Nanoparticles Exacerbate Hyperthermia Induced Blood-Brain Barrier Breakdown, Cognitive Dysfunction and Brain Pathology in the Rat : Neuroprotective Effects of Nanowired-Antioxidant Compound H-290/51
- 2009
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In: Journal of Nanoscience and Nanotechnology. - 1533-4880 .- 1533-4899. ; 9:8, s. 5073-5090
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Journal article (peer-reviewed)abstract
- The possibility that chronic exposure of nanoparticles may alter stress reaction and brain pathology following hyperthermia was examined in a rat model. Engineered nanoparticles from Ag or M Cu (approximate to 50-60 nm) were administered (30 mg/kg, i.p.) once daily for 1 week in young male rats. M On the 8th day these animals were subjected to 4 h heat stress at 38 degrees C in a BOD incubator. In these animals stress symptoms, blood-brain barrier (BBB) permeability, cognitive and motor functions and brain pathology were examined. Subjection of nanoparticle treated rats to heat stress showed exacerbation of stress symptoms i.e., hyperthermia, salivation and prostration and exhibited greater BBB disruption, brain edema formation, impairment of cognitive and motor functions M and brain damage compared to normal animals. This enhanced brain pathology in heat stress was most marked in animals that received Ag nanoparticles compared to Cu treatment. Treatment with antioxidant compound H-290/51 either 30 min or 60 min after heat stress did not alter hyperthermia M induce brain pathology in nanoparticle treated rats. Whereas, administration of nanowired-H-290/51 after 30 min or 60 min heat stress markedly attenuated BBB disruption, sensory motor function and brain pathology. These results suggest that chronic nanoparticles treatment exacerbate hyperthermia induced brain pathology that is significantly attenuated by nanowired but not normal H-290/51 compound. Taken together, our observations suggest that nano-wired drug delivery of H-290/51 is a promising approach to induce neuroprotection in hyperthermia induced brain pathology, not reported earlier.
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| 4. |
- Sharma, Hari Shanker, et al.
(author)
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Cocaine-Induced Breakdown of the Blood–Brain Barrier and Neurotoxicity
- 2009
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In: International review of neurobiology. - 0074-7742 .- 2162-5514. ; 88, s. 297-334
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Research review (peer-reviewed)abstract
- Role of cocaine in influencing blood-brain barrier (BBB) function is still unknown. Available evidences suggest that cocaine administration results in acute hyperthermia and alterations in brain serotonin metabolism. Since hyperthermia is capable to induce the breakdown of the BBB either directly or through altered serotonin metabolism, a possibility exists that cocaine may induce neurotoxicity by causing BBB disruption. This hypothesis is discussed in this review largely based on our own laboratory investigations. Our observations in rats demonstrate that cocaine depending on the dose and routes of administration induces profound hyperthermia, increased plasma and brain serotonin levels leading to BBB breakdown and brain edema formation. Furthermore, cocaine was able to enhance cellular stress as seen by upregulation of heat shock protein (HSP 72 kD) expression and resulted in marked neuronal and glial cell damages at the time of the BBB dysfunction. Taken together, these observations are the first to suggest that cocaine-induced BBB disruption is instrumental in precipitating brain pathology. The possible mechanisms of cocaine-induced BBB breakdown and neurotoxicity are discussed.
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| 5. |
- Sharma, Hari Shanker, et al.
(author)
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Conference Scene : New perspectives on nanoneuroscience, nanoneuropharmacology and nanoneurotoxicology
- 2009
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In: Nanomedicine (London, England). - : Future Medicine Ltd. - 1748-6963 .- 1743-5889. ; 4:5, s. 509-513
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Journal article (peer-reviewed)abstract
- The 6th GCNN Annual meeting was held in the Hilton Hotel, Vienna, Austria, on 1-4 March, 2009. In this conference a special focus was given to 'Nanomedicine: Nanoneuropharmacology and Nanoneurotoxicity' on 2-3 March, 2009. The 'Nanomedicine Focus' was organized by M Robertson (London, UK) and H Shanker Sharma (Uppsala, Sweden) and was divided into three sessions on 2 March, followed by one session on 3 March. In total, 11 speakers participated in these sessions covering more than 5 h of intensive presentations intermingled with lively discussions from the audience.
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| 6. |
- Sharma, Hari Shanker, et al.
(author)
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Drug delivery to the spinal cord tagged with nanowire enhances neuroprotective efficacy and functional recovery following trauma to the rat spinal cord
- 2007
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In: Neuroprotective agents. - : Wiley. - 9781573316859 ; , s. 197-218
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Conference paper (peer-reviewed)abstract
- The possibility that drugs attached to innocuous nanowires enhance their delivery within the central nervous system (CNS) and thereby increase their therapeutic efficacy was examined in a rat model of spinal cord injury (SCI). Three compounds-AP173 (SCI-1), AP713 (SCI-2), and AP364 (SCI-5) (Acure Pharma, Uppsala, Sweden)-were tagged with TiO2-based nanowires using standard procedure. Normal compounds were used for comparison. SCI was produced by making a longitudinal incision into the right dorsal horn of the T10-T11 segments under Equithesin anesthesia. The compounds, either alone or tagged with nanowires, were applied topically within 5 to 10 min after SCI. In these rats, behavioral outcome, blood-spinal cord barrier (BSCB) permeability, edema formation, and cell injury were examined at 5 h after injury. Topical application of normal compounds in high quantity (10 mu g in 20 mu L) attenuated behavioral dysfunction (3 h after trauma), edema formation, and cell injury, as well as reducing BSCB permeability to Evans blue albumin and I-131. These beneficial effects are most pronounced with AP713 (SCI-2) treatment. Interestingly, when these compounds were administered in identical conditions after tagging with nanowires, their beneficial effects on functional recovery and spinal cord pathology were further enhanced. However, topical administration of nanowires alone did not influence trauma-induced spinal cord pathology or motor functions. Taken together, our results, probably for the first time, indicate that drug delivery and therapeutic efficacy are enhanced when the compounds are administered with nanowires.
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| 7. |
- Sharma, Hari S., et al.
(author)
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Influence of Engineered Nanoparticles from Metals on the Blood-Brain Barrier Permeability, Cerebral Blood Flow, Brain Edema and Neurotoxicity : An Experimental Study in the Rat and Mice Using Biochemical and Morphological Approaches
- 2009
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In: Journal of Nanoscience and Nanotechnology. - 1533-4880 .- 1533-4899. ; 9:8, s. 5055-5072
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Journal article (peer-reviewed)abstract
- Influence of nanoparticles on brain function following in vivo exposures is not well known. Depending on the magnitude and intensity of nanoparticle exposure from the environment, food and/or water source, neuronal function could be affected and may lead to neurotoxicity and neuropathology. This hypothesis was examined in present investigation using systemic or intracerebroventricular administration of engineered nanoparticles from metals, i.e., Al, Ag and Cu (approximate to 50 to 60 nm) on neurotoxicity in rats and mice. Intraperitoneal (50 mg/kg), intravenous (30 mg/kg), intracarotid (2.5 mg/kg) or intracerebroventricular administration (20 mu g) of nanoparticles significantly altered the blood-brain barrier (BBB) function to Evans blue and radioiodine in several regions of the brain and spinal cord at 24 h after their administration. Marked decreases in local cerebral blood flow (CBF) and pronounced brain edema was seen in regional areas associated with BBB leakage. Neuronal cell injuries, glial cell activation, heat shock protein (HSP) upregulation and loss of myelinated fibers are quite common in effected brain areas. The observed pathological changes were most pronounced in mice compared to rats. Exposures to Cu and Ag nanoparticles showed most marked effects on brain pathology when administered into systemic circulation or into the brain ventricular spaces as compared to Al nanoparticles. Our results are the first to show that nanoparticles from metals are able to induce selective and specific neurotoxicity that depends on the type of metals, route of administration and the species used.
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| 8. |
- Sharma, Hari S., et al.
(author)
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Nano-Drug Delivery and Neuroprotection in Spinal Cord Injury
- 2009
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In: Journal of Nanoscience and Nanotechnology. - 1533-4880 .- 1533-4899. ; 9:8, s. 5014-5037
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Journal article (peer-reviewed)abstract
- Recently nano-drug delivery to the central nervous system (CNS) has been shown to be more effective than the parent compound by itself. An increased availability of the drug for longer periods to the brain or spinal cord and/or a decrease in the drug metabolism altogether could lead to potentiation of the pharmacological activity of the nano-delivered compounds. However, it is still unclear whether the nanocarriers used to deliver the drugs may itself has any potential neurotoxic activity. Although, nanodrug-delivery appears to be a quite promising therapeutic tool for the future clinical therapy, its advantages and limitations for the routine use of patients still needs to be elucidated. Our laboratory is engaged to study a plethora of potential neuroprotective novel compounds delivered to the CNS using nanowiring techniques following brain or spinal cord trauma. Our investigations show that nanowired drugs, if delivered locally following spinal cord injury achieve better neuroprotection than the parent compounds. This effect of nano-drug delivery appears to be very selective in nature. Thus, a clear differentiation based on the compounds used for nano-drug delivery can be seen on various pathological parameters in spinal cord injury. These observations suggest that nanowiring may itself do not induce neuroprotection, but enhance the neuroprotective ability of compounds after trauma. This review describes some recent advances in nano-drug delivery to the CNS in relation to novel neuroprotective strategies with special emphasis on spinal cord trauma based on our own observations and recent findings from our laboratory investigations.
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| 9. |
- Sharma, Hari Shanker, et al.
(author)
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Nanoparticles aggravate heat stress induced cognitive deficits, blood-brain barrier disruption, edema formation and brain pathology
- 2007
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In: Progress in Brain Research. - 0079-6123 .- 1875-7855. ; 162, s. 245-273
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Research review (peer-reviewed)abstract
- Our knowledge regarding the influence of nanoparticles on brain function in vivo during normal or hyperthermic conditions is still lacking. Few reports indicate that when nanoparticles enter into the central nervous system (CNS) they may induce neurotoxicity. On the other hand, nanoparticle-induced drug delivery to the brain enhances neurorepair processes. Thus, it is likely that the inclusion of nanoparticles in body fluid compartments alters the normal brain function and/or its response to additional stress, e.g., hyperthermia. New data from our laboratory show that nanoparticles derived from metals (e.g., Cu, Ag or Al, approximately 50-60nm) are capable of inducing brain dysfunction in normal animals and aggravating the brain pathology caused by whole-body hyperthermia (WBH). Thus, normal animals treated with nanoparticles (for 1 week) exhibited mild cognitive impairment and cellular alterations in the brain. Subjection of these nanoparticle-treated rats to WBH resulted in profound cognitive and motor deficits, exacerbation of blood-brain barrier (BBB) disruption, edema formation and brain pathology compared with naive animals. These novel observations suggest that nanoparticles enhance brain pathology and cognitive dysfunction in hyperthermia. The possible mechanisms of nanoparticle-induced exacerbation of brain damage in WBH and its functional significance in relation to our current knowledge are discussed in this review.
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| 10. |
- Sharma, Hari Shanker, et al.
(author)
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Nanoparticles influence pathophysiology of spinal cord injury and repair
- 2009
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In: Progress in Brain Research. - Amsterdam : Elsevier. - 0079-6123 .- 1875-7855. - 9780444534316 ; 180, s. 155-180
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Research review (peer-reviewed)abstract
- Spinal cord injury (SCI) is a serious clinical problem for which no suitable therapeutic strategies have been worked out so far. Recent studies suggest that the SCI and its pathophysiological responses could be altered by systemic exposure to nanoparticles. Thus, SCI when made in animals intoxicated with engineered nanoparticles from metals or silica dust worsened the outcome. On the other hand, drugs tagged with titanium (TiO2) nanoparticles or encapsulated in liposomes could enhance their neuroprotective efficacy following SCI. Thus, to expand our knowledge on nanoparticle-induced alterations in the spinal cord pathophysiology further research is needed. These investigations will help to develop new strategies to achieve neuroprotection in SCI, for example, using nanodrug delivery. New results from our laboratory showed that nanoparticle-induced exacerbation of cord pathology following trauma can be reduced when the suitable drugs tagged with TiO2 nanowires were administered into the spinal cord as compared to those drugs given alone. This indicates that nanoparticles depending on the exposure and its usage could induce both neurotoxicity and neuroprotection. This review discusses the potential adverse or therapeutic utilities of nanoparticles in SCI largely based on our own investigations. In addition, possible mechanisms of nanoparticle-induced exacerbation of cord pathology or enhanced neuroprotection following nanodrug delivery is described in light of recently available data in this rapidly emerging field of nanoneurosciences.
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