Nanoneuroscience: Emerging Concepts on Nanoneurotoxicity and Nanoneuroprotection
2007; Future Medicine; Volume: 2; Issue: 6 Linguagem: Inglês
10.2217/17435889.2.6.753
ISSN1748-6963
Autores Tópico(s)Anesthesia and Neurotoxicity Research
ResumoNanomedicineVol. 2, No. 6 EditorialFree AccessNanoneuroscience: emerging concepts on nanoneurotoxicity and nanoneuroprotectionHari Shanker SharmaHari Shanker SharmaUppsala Univervisty, University Hospital, Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Division of Anesthesiology & Intensive Care medicine, SE-75185 Uppsala, Sweden. Published Online:20 Dec 2007https://doi.org/10.2217/17435889.2.6.753AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Figure 1. The concept of (A) blood–brain and (B) brain–blood barriers.Nanoparticles, when administered within the lumen (A) or into the brain microenvironment (B), are normally prevented from crossing the endothelial cell membrane barriers. However, under disease conditions, these barriers could be broken down to enable enhanced passage of nanoparticles and serum proteins.Alternatively, after attaching to the endothelial cell membrane, nanoparticles might disrupt the barrier or induce cellular stress to alter the function of the blood–brain and brain–blood barriers. Adapted from [12,13].Figure 2. Extravasation of Evans blue on the (A) dorsal and (B) ventral surfaces of rat brain after Ag nanoparticle treatment.The Ag nanoparticle was administered intravenously (35 mg/kg) and the rat is allowed to survive for 24 h after injection. Coronal sections of the brain (C) passing through hippocampus and (D) caudate nucleus are also shown.Leakage of Evans blue dye can be seen in various brain regions (arrows). The deeper parts of the brain (e.g., hippocampus, caudate nucleus, thalamus, hypothalamus and cortical layers, including pyriform, cingulate, parietal and temporal cortices) showed moderate blue staining. This indicates widespread leakage of Evans blue albumin within the brains after Ag treatment. Bar = 3 mm Adapted from [14].Figure 3. Nanowire characterization.(A) SEM and TEM characterizations of nanowire film, showing a SEM photograph of the white, flexible and assembled nanowire membrane and a TEM picture (inset) for confirming the nanowire morphology (scale bar: 50 nm).(B) An EDX spectrum of the titanate nanowire membrane.EDX: Energy dispersive x-ray; SEM: Scanning-electron microscope;TEM: Transmission-electron microscope. Adapted from [18].Recently, nanotechnology has acquired a new dimension in medicine and healthcare, and its use in various therapeutic aspects, for example, drug delivery to chemotherapy, are increasing day by day [1]. Apart from their therapeutic use, nanoparticles are often used for diagnostic purposes to monitor disease progression or drug-induced repair mechanisms in human biological systems through the use of engineered nanoparticles, nanodevices and/or nanomaterials. This phenomenon has resulted in a substantial growth of nanopharmaceuticals that can be used for our future therapeutic needs in treating various diseases. However, the effects of nanoparticles per se on biological systems should not be ignored while developing nano-based medicine as future therapy. Current research using nanoparticles in human health systems is still preliminary and is based largely on cell culture studies. Only a few sporadic investigations deal with the in vivo effects of nanoparticles on biological systems.Effect of nanoparticles on brain function in vivo is necessaryUnfortunately, the effects of nanoparticles on CNS function in vivo situations are still lacking (Table 1). Available in vivo data show that nanoparticles could influence drug delivery to the brain [1–3], and that they have the capacity to bypass the blood–brain barrier (BBB) [4]. However, the effect of nanoparticles on BBB dysfunction and related consequences (e.g., brain pathology) is still not well known (Table 1). Thus, new investigations dealing with the effects of several kinds of nanoparticles on the CNS with special regard to BBB function is urgently needed.Nanoparticles might influence blood–brain barrier function & brain pathologyOne of the goals of clinicians in treating brain diseases is to find new ways to enhance drug delivery to the CNS. Thus, several laboratories have attempted to show enhanced delivery of drugs to the CNS through the use of nanoparticles. However, the toxic effects of these nanoparticles when they cross the BBB or reach the brain fluid microenvironment have not been examined in detail. Thus, our understanding of the role of nanoparticles on the BBB function in itself is lacking, and requires carefully controlled further investigations.The blood–brain barrier: a gateway to neurological diseasesOne of the principle regulatory mechanisms controlling drug delivery to the brain is the BBB. The BBB regulates the composition of the fluid microenvironment of the brain strictly within a narrow limit [5,6]. Even a slight alteration in the brain fluid microenvironment in which neurons and glial cells are suspended leads to altered brain function [5,6]. Anatomically, the BBB resides in the endothelial cells of the cerebral microvessels that are connected with tight junctions [6]. These CNS endothelial cells also lack vesicular transport (Figure 1). Thus, the permeability property of the BBB is comparable with that of an extended plasma membrane [5,6]. Accordingly, lipid-soluble substances permeate across the BBB easily, and the lipid-insoluble compounds are largely excluded [7]. The normal BBB does not allow proteins to pass from the vascular compartments to the cerebral compartment to avoid edema formation [8].Under normal conditions, nanoparticles do not cross the BBB. This is evident by the fact that lanthanum (molecular diameter 12 Å), an electron-dense tracer, is stopped at the luminal tight junctions of the BBB [9]. However, a direct disruption of the cell membrane caused by nanoparticles will allow their entry into the brain [10]. Breakdown of the BBB enables the passage of various serum components, including proteins and other toxic substances, into the brain microfluid environment. This could result in brain edema formation leading to CNS pathology [8,11]. Thus, the BBB has an important role as a gateway to brain disease. Obviously, the influence of nanoparticles on brain function is thus dependent on their ability to modify BBB function. This aspect must be examined in great detail.Luminal versus abluminal BBB functionApart from barrier function from blood to brain, a similar, if not identical barrier also exists between the brain and blood. A barrier between brain and blood is necessary to stop the passage of various neurochemicals released within the brain to reach systemic circulation. It is likely that, in CNS diseases, the barrier between brain and blood is also compromised [12,13]. Although most studies are confined to the study of the luminal barrier function (i.e., transport of substrates from blood to brain), investigations on the alteration in the abluminal barrier dysfunction from brain to blood are largely ignored.A normal function of the BBB is obviously crucial for the maintenance of the CNS function (Figure 1). A leaky abluminal barrier will enable passage of various vasoactive or toxic substances from the brain to the bloodstream that might have rebound consequences on CNS function. Whether disruption of the luminal barrier function in disease conditions is always accompanied with similar damage to the abluminal barrier properties is not known and requires further investigation.Thus, increased understanding of the transport properties of nanoparticles across the BBB and the role of the BBB in health and diseases is needed to expand our knowledge regarding the role of nanomedicine in neuroprotection and/or neurotoxicity.Neuroprotection & neurotoxicity: neural & non-neural cells are equally importantThe term 'neuroprotection' normally denotes rescuing of nerve cells [12,13]. The number of non-neural cells far exceeds the number of neurons in the CNS [13](Figure 1). The term 'neuroprotection' thus appears to be misleading, because neurons are in the minority in the CNS and their function depends largely on the survival of non-neural cells and vice versa. Thus, the non-neural cells (i.e., glial cells and endothelial cells) are equally important for CNS function in health and disease [13].In almost all cases of experimental or clinical brain diseases, the structure and functions of the neurons, glial and endothelial cells are compromised considerably [5–8]. To ensure the normal function of neurons by pharmacological means, revival of glial and endothelial cell functions is equally important [5–8]. Experimental evidence from our laboratory indicates that repair of BBB function by pharmacological means attenuates neuronal and glial cell damage in different models of CNS injuries [14]. Thus, the effects of nanoparticles on CNS function might be examined in relation to their possible effects on neurons, glia cells and endothelial cells. This approach will enhance our basic understanding of nanomedicine in neuroprotection and/or neurodegeneration.Nanoneurotoxicity: a fast emerging disciplineRecent observations suggest that nanoparticles are able to induce considerable neurotoxicity [10]. Most nanoparticles are formed from transition metals, silver, copper, aluminum, silicon, carbon and metal oxides. Owing to their size, these nanoparticles can either cross the BBB easily and/or produce damage to barrier integrity. Nanoparticles can enter into body fluid environments through inhalation from the environment [15] and could be incorporated into a variety of non-neural cells through endocytosis [16], where they reside there for weeks to months [10]. The potential risks and the cellular toxicity imposed by these nanoparticles per se are still unknown. It is likely that nanoparticles in the circulation will induce endothelial cell membrane toxicity and/or disrupt tight junctions. In addition, nanoparticles can stimulate vesicular transport to gain access into the CNS microenvironment (Figure 1). Alternatively, nanoparticles induce oxidative stress and generate free radicals that could disrupt the endothelial cell membrane causing BBB dysfunction [10].Nanoparticles disrupt the BBBResearch from our laboratory shows that intravenous (30 mg/kg), intraperitoneal (50 mg/kg) or intracerebral (20 µg in 10 µl) administration of Ag, Cu or Al nanoparticles (~50–60 nm) disrupt the BBB to Evans blue albumin in rats and mice in a highly selective and specific manner (Figure 2). Interestingly, aluminum nanoparticles exerted only a minimal effect on BBB function compared with the silver and copper nanoparticles in identical doses [10,14](Figure 2). The BBB to Evans blue dye was least affected following intraperitoneal administration of these nanoparticles.In these experiments, BBB disruption with nanoparticles is associated with neurotoxicity in areas showing Evans blue leakage [10,14]. The magnitude of neurotoxic effects corresponds closely to the intensity of BBB breakdown (Sharma HS, Unpublished Data). Thus, the nerve cell, glial cell and myelin changes were most prominent in the brain or spinal cord areas exhibiting BBB disruption. This indicates that the breakdown of the BBB by nanoparticles is instrumental in neurotoxicity.Thus, the route of administration of nanoparticles and their particulate chemistry are important factors in inducing BBB dysfunction and brain pathology. However, further studies using dose- and size-related effects of nanoparticles are needed to understand their effects on neurotoxicity in vivo.Nanoneuroprotection: nano-drug delivery is an effective means to potentiate & prolong drug effects in the CNSKwon and colleagues showed that toxin-coated silica nanowires could enter into cultured human cells and deliver a lethal dose of the toxin. Their work further shows that nanowires and other nanomaterials coated with the protein fibronectin can penetrate tumors more easily [17]. These observations suggest that nanowires coated with drugs can be used to induce effective neuroprotection in CNS injuries as well.New roles of nanoparticle-induced drug delivery in traumatic CNS injuriesUsing a drug coating of TiO2-based nanowires (hydrogen titanate) (Figure 3) with a typical diameter of 50–60 nm for enhanced drug delivery to the spinal cord following injury, our laboratory showed that the therapeutic efficacy of nanowired drugs is considerably enhanced compared with the compounds given alone [18]. Thus, topical administration of nanowired compounds AP173, AP713 and AP364 exerted superior effects on trauma-induced disturbances in the sensory motor functions, breakdown of the blood–spinal cord barrier (BSCB), edema formation and cord pathology compared with the parent compounds. It appears that the nanowired compounds might have greater accessibility within the cord to exert their actions on neural cells and receptors compared with the parent compounds. As nanowires alone do not induce any beneficial effects on motor function or spinal cord pathology following trauma, a combination of drugs with nanowires is important to have superior neuroprotective effects in spinal cord trauma.New roles of nanoparticles in treating drug addictionA new role for nanoparticles in psychostimulant-induced dependence appears to be emerging. Thus, microinjection of glial-derived neurotrophic factor (GDNF)-conjugated nanoparticles into the rat striatum and nucleus accumbens is able to block self-administration of cocaine in rats [19]. Experiments performed in our laboratory showed that conjugation of nanoparticles with AP-267, a serotonin-modulating compound, potentiated its neuroprotective effects on methamphetamine-induced hyperthermia, behavioral symptoms and BBB breakdown. This indicates that nanoparticle-conjugated drugs could be a promising tool in the future for treatment of drug addiction.It appears that an increased bioavailability of nanowired drugs owing to reduced biodegradation [20,21] and/or long-term binding or potentiation of their effects on receptors [18] and/or intracellular signal transduction mechanisms [10] could be responsible for the enhanced neuroprotective effects of nanowired-drugs [18]. However, further investigations are needed in this direction to understand this phenomena.Nanoparticles exacerbate stress reaction: a cautious approachRecent observations show that chemotherapy-induced hyperthermia enhanced penetration of quantum dots in cells in the breast tissues significantly [22]. This resulted in increased cell membrane damage, resulting in aggravation of cell and tissue injuries [10]. This indicates that distribution and/or effects of nanoparticles in the CNS could also be influenced by hyperthermia caused by various factors (e.g., heat stress, exercise in hot environment or psychostimulant drugs) [23]. Alternatively, the effects of nanoparticles on brain function could be altered by additional stress or environmental factors.New data from our laboratory show that the effects of engineered nanoparticles from metals (e.g., Cu, Ag or Al, ~50–60 nm) on BBB disruption and brain pathology are enhanced considerably 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 BBB disruption, edema formation and brain pathology [10]. These observations suggest that nanoparticle-induced brain function could be dependent on external (environmental) or internal (body temperature) factors.Thus, further studies in nanomedicine should be directed to find out whether genetic, environmental (high industrial pollution, ambient temperatures) or biological factors (cardiovascular, endocrine or metabolic diseases) could alter the effects of nanoparticles in the CNS. These investigations will shed new light on nanoparticle-induced drug delivery to the brain for therapeutic purposes.Table 1. PubMed hits using 'nanoparticles' alone and in combination with various terms related to brain function and pathology.Search titlesNumber of hitsNanoparticles11657Combination (&) Brain315Brain function201Spinal cord15Spinal cord function13Blood–brain barrier132Blood–CSF barrier3Blood–spinal cord barrier2Brain pathology85Brain toxicity35Brain protection4Brain drug delivery143Drug addiction1Hyperthermia79Stress160Heat stress5Toxicity512Nanoneurotoxicology0Nanoneuropharmacology0Nanoneuroscience0Nanomedicine304Source: PubMed citations: searched on September 25, 2007.Financial & competing interests disclosurePart of the investigation on 'nanoneuroscience' in HS Sharma's laboratory is supported by Funds from European Office of Aerospace Research and Development (EOARD), US Office of Air Force Research (ASAF), US Military London Office, London, UK; Astra Zeneca, Mölndal, Sweden; Acure Pharma, Sweden; and Ebewe Pharma, Austria. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.The views expressed in this article are solely those of HS Sharma based on their own investigation and according to the current available literature and do not represent the opinion of Uppsala University or any other organization mentioned above.No writing assistance was utilized in the production of this manuscript.Bibliography1 Kreuter J: Nanoparticles – a historical perspective. Int. J. Pharm.331(1),1–10 (2007).Crossref, Medline, CAS, Google Scholar2 Kreuter J: Nanoparticulate systems in drug delivery and targeting. J. Drug Target.3(3),171–173 (1995).Crossref, Medline, Google Scholar3 Schroder U, Sabel BA: Nanoparticles, a drug carrier system to pass the blood–brain barrier, permit central analgesic effects of i.v. dalargin injections. Brain Res.710(1–2),121–124 (1996).Crossref, Medline, Google Scholar4 Olivier JC: Drug transport to brain with targeted nanoparticles. NeuroRx.2(1),108–119 (2005).Crossref, Medline, Google Scholar5 Sharma HS, Westman J: The Blood-Spinal Cord and Brain Barriers in Health and Disease. Elsevier Academic Press. San Diego, CA, USA 1–617 (2004).Google Scholar6 Rapoport SI: The Blood–Brain Barrier in Physiology and Medicine. Raven Press, NY, USA 1–316 (1976).Google Scholar7 Sharma HS, Johanson CE: Blood–cerebrospinal fluid barrier in hyperthermia. Prog. Brain Res.162,459–478 (2007).Google Scholar8 Sharma HS: Hyperthermia induced brain oedema: current status and future perspectives. Indian J. Med. Res.123(5),629–652 (2006).Medline, Google Scholar9 Sharma HS: Pathophysiology of blood–spinal cord barrier in traumatic injury and repair. Curr. Pharm. Des.11(11),1353–1389 (2005).Crossref, Medline, Google Scholar10 Sharma HS, Sharma A: Nanoparticles aggravate heat stress induced cognitive deficits, blood–brain barrier disruption, edema formation and brain pathology. Prog. Brain Res.162,245–273 (2007).Crossref, Medline, CAS, Google Scholar11 Kiyatkin EA, Brown PL, Sharma HS: Brain edema and breakdown of the blood–brain barrier during methamphetamine intoxication: critical role of brain hyperthermia. Eur. J. Neurosci.26(5),1242–1253 (2007).Crossref, Medline, Google Scholar12 Sharma HS: Neurodegeneration and neuroregeneration: recent advancements and future perspectives. Curr. Pharm. Des.13(18),1825–1827 (2007).Crossref, Medline, CAS, Google Scholar13 Sharma HS: Neurotrophic factors in combination: a possible new therapeutic strategy to influence pathophysiology of spinal cord injury and repair mechanisms. Curr. Pharm. Des.13(18),1841–1874 (2007).Crossref, Medline, Google Scholar14 Sharma HS. Chapter 11: Blood–Central Nervous System Barriers: The Gateway to Neurodegeneration, Neuroproetction, and Neuroregeneration. In: Handbook of Neurochemistry 24. Lajtha A (Ed.). 1–98 (In press) (2007).Google Scholar15 Borm PJ, Robbins D, Haubold S et al.: The potential risks of nanomaterials: a review carried out for ECETOC. Part. Fibre Toxicol.3,11 (2006).Crossref, Medline, Google Scholar16 Kim JS, Yoon TJ, Yu KN et al.: Cellular uptake of magnetic nanoparticle is mediated through energydependent endocytosis in A549 cells. J. Vet. Sci.7(4),321–326 (2006).Crossref, Medline, Google Scholar17 Kwon NH, Beaux MF 2nd, Ebert C et al.: Nanowire-based delivery of Escherichia coli O157 shiga toxin 1 A subunit into human and bovine cells. Nano Lett.7(9),2718–2723 (2007).Crossref, Medline, CAS, Google Scholar18 Sharma HS, Ali SF, Dong W et al.: Drug-delivery to the spinal cord tagged with nanowire enhances neuroprotective efficacy and functional recovery following trauma to the rat spinal cord. Ann. N. Y. Acad. Sci.1403, (In press) (2007).Google Scholar19 Green-Sadan T, Kuttner Y, Lublin-Tennenbaum T et al.: Glial cell line-derived neurotrophic factor-conjugated nanoparticles suppress acquisition of cocaine self-administration in rats. Exp. Neurol.194(1),97–105 (2005).Crossref, Medline, Google Scholar20 Vyas TK, Tiwari SB, Amiji MM: Formulation and physiological factors influencing CNS delivery upon intranasal administration. Crit. Rev. Ther. Drug Carrier Syst.23(4),319–347 (2006).Medline, Google Scholar21 Emerich DF, Thanos CG: The pinpoint promise of nanoparticle-based drug delivery and molecular diagnosis. Biomol. Eng.23(4),171–184 (2006).Crossref, Medline, CAS, Google Scholar22 Minet O, Dressler C, Beuthan J: Heat stress induced redistribution of fluorescent quantum dots in breast tumor cells. J. Fluoresc.14(3),241–247 (2006).Crossref, Google Scholar23 Sharma HS, Ali SF: Alterations in blood–brain barrier function by morphine and methamphetamine. Ann. NY Acad. Sci.1074,198–224 (2006).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited BySurgical cotton microfibers loaded with proteins and apatite: A potential platform for bone tissue engineeringInternational Journal of Biological Macromolecules, Vol. 236The Effect of Aqueous Solution of Silver Nanoparticles on Rat Behavior21 May 2022 | Nanobiotechnology Reports, Vol. 17, No. 2PrefacePrefaceMethamphetamine exacerbates pathophysiology of traumatic brain injury at high altitude. Neuroprotective effects of nanodelivery of a potent antioxidant compound H-290/51Cerebrolysin restores balance between excitatory and inhibitory amino acids in brain following concussive head injury. 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Soc. Rev., Vol. 43, No. 10New perspectives of nanoneuroprotection, nanoneuropharmacology and nanoneurotoxicity: modulatory role of amino acid neurotransmitters, stress, trauma, and co-morbidity factors in nanomedicine11 September 2013 | Amino Acids, Vol. 45, No. 5Safety of Engineered Nanomaterials and OH&S Issues for Commercial-Scale Production12 September 2013Transport of Nanoparticles across Blood–Brain Barrier16 July 2013Exposure to silver nanoparticles does not affect cognitive outcome or hippocampal neurogenesis in adult miceEcotoxicology and Environmental Safety, Vol. 87Nanotoxicology, Vol. 7, No. 5Nanowired drug delivery for neuroprotection in central nervous system injuries: modulation by environmental temperature, intoxication of nanoparticles, and comorbidity factors8 December 2011 | WIREs Nanomedicine and Nanobiotechnology, Vol. 4, No. 2Neurological SystemHealth implications of engineered nanomaterialsNanoscaleNanotechnology for Cerebral Delivery of Nutraceuticals for the Treatment of Neurodegenerative Diseases30 August 2011Microglial activation, recruitment and phagocytosis as linked phenomena in ferric oxide nanoparticle exposureToxicology LettersExposure to silver nanoparticles induces oxidative stress and memory deficits in laboratory ratsOpen Life Sciences, Vol. 6, No. 4Early microvascular reactions and blood–spinal cord barrier disruption are instrumental in pathophysiology of spinal cord injury and repair: novel therapeutic strategies including nanowired drug delivery to enhance neuroprotection16 December 2010 | Journal of Neural TransmissionNeurotherapeutic applications of nanoparticles in Alzheimer's diseaseJournal of Controlled ReleaseDrug delivery to the CNS and polymeric nanoparticulate carriersFuture Medicinal Chemistry, Vol. 2, No. 11Potential neurotoxicity of nanoparticlesInternational Journal of Pharmaceutics, Vol. 394, No. 1-2New perspectives on molecular and cellular mechanisms of neuroprotection and neuroregeneration: part I9 January 2014 | Expert Review of Neurotherapeutics, Vol. 10, No. 7Conference Scene: Nanoneuroprotection and nanoneurotoxicity: recent progress and future perspectivesHari Shanker Sharma & Aruna Sharma8 June 2010 | Nanomedicine, Vol. 5, No. 4Nanotechnology applications and approaches for neuroregeneration and drug delivery to the central nervous system29 April 2010 | Annals of the New York Academy of Sciences, Vol. 1199, No. 1Nanowired-Drug Delivery Enhances Neuroprotective Efficacy of Compounds and Reduces Spinal Cord Edema Formation and Improves Functional Outcome Following Spinal Cord Injury in the Rat31 August 2009A New Antioxidant Compound H-290/51 Attenuates Nanoparticle Induced Neurotoxicity and Enhances Neurorepair in Hyperthermia31 August 2009Influence of Nanoparticles on Blood–Brain Barrier Permeability and Brain Edema Formation in Rats31 August 2009Brain Protection in Neuropsychiatric Disorders: Past, Present and Future Challenges19 February 2010Breakdown of the Blood-Brain Barrier in Stress Alters Cognitive Dysfunction and Induces Brain Pathology: New Perspectives for Neuroprotective Strategies19 February 2010Glia activation induced by peripheral administration of aluminum oxide nanoparticles in rat brainsNanomedicine: Nanotechnology, Biology and Medicine, Vol. 5, No. 4Apoptosis induced by titanium dioxide nanoparticles in cultured murine microglia N9 cells10 November 2009 | Chinese Science Bulletin, Vol. 54, No. 20Conference Scene: New perspectives on nanoneuroscience, nanoneuropharmacology and nanoneurotoxicologyHari Shanker Sharma & Aruna Sharma3 July 2009 | Nanomedicine, Vol. 4, No. 5Nanoparticles influence pathophysiology of spinal cord injury and repairPrefaceNanomedicine Nanotechnology Biology and Medicine, Vol. 5, No. 4Introducing Nanoneuroscience as a Distinct Discipline30 November 2009The 14th International Symposium on Brain Edema and Brain Tissue InjuryHari Shanker Sharma28 October 2008 | Future Neurology, Vol. 3, No. 6New perspectives for the treatment options in spinal cord injury20 October 2008 | Expert Opinion on Pharmacotherapy, Vol. 9, No. 165th Annual Global College of Neuroprotection and NeuroregenerationExpert Review of Neurotherapeutics, Vol. 8, No. 6 Vol. 2, No. 6 Follow us on social media for the latest updates Metrics History Published online 20 December 2007 Published in print December 2007 Information© Future Medicine LtdFinancial & competing interests disclosurePart of the investigation on 'nanoneuroscience' in HS Sharma's laboratory is supported by Funds from European Office of Aerospace Research and Development (EOARD), US Office of Air Force Research (ASAF), US Military London Office, London, UK; Astra Zeneca, Mölndal, Sweden; Acure Pharma, Sweden; and Ebewe Pharma, Austria. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.The views expressed in this article are solely those of HS Sharma based on their own investigation and according to the current available literature and do not represent the opinion of Uppsala University or any other organization mentioned above.No writing assistance was utilized in the production of this manuscript.PDF download
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