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Exacerbation of Brain Pathology After Partial Restraint in Hypertensive Rats Following SiO2 Nanoparticles Exposure at High Ambient Temperature

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Abstract

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 SiO2 intoxication further exacerbated these brain pathologies and cognitive dysfunctions.

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Acknowledgments

This investigation is partially supported by the Air Force Office of Scientific Research (London), Air Force Material Command, USAF, under grant number FA8655-05-1-3065. The US Government is authorized to reproduce and distribute reprints for Government purpose notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the Air Force Office of Scientific Research or the US Government. Financial support of Swedish Medical Research Council (Grant No. 2710, HSS); Astra-Zeneca, Mölndal, Sweden (HSS), Alexander von Humboldt Foundation, Germany (HSS); India-EU Research Co-operation (AS/RP), Ministry of Science and Technology, Government of India, New Delhi, India (AS/RP) and University Grants Commission, New Delhi, India (HSS); Indian Council of Medical Research, New Delhi, India (HSS) is gratefully acknowledged. The authors have no conflict of interest with any agencies mentioned above.

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Authors and Affiliations

  1. Laboratory of Cerebrovascular Research, Departmen of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, Frödingsgatan 12, 75421, Uppsala, Sweden

    Hari S. Sharma & Aruna Sharma

  2. Department of Neurology, University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Dafin F. Muresanu

  3. Indian Institute of Technology, Department of Biomaterials, School of Biomedical Engineering, Banaras Hindu University, Varanasi, India

    Ranjana Patnaik

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  1. Hari S. Sharma
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  2. Dafin F. Muresanu
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  3. Ranjana Patnaik
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  4. Aruna Sharma
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Correspondence to Hari S. Sharma.

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Sharma, H.S., Muresanu, D.F., Patnaik, R. et al. Exacerbation of Brain Pathology After Partial Restraint in Hypertensive Rats Following SiO2 Nanoparticles Exposure at High Ambient Temperature. Mol Neurobiol 48, 368–379 (2013). https://doi.org/10.1007/s12035-013-8502-y

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  • DOI: https://doi.org/10.1007/s12035-013-8502-y

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