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Nanowired Delivery of Growth Hormone Attenuates Pathophysiology of Spinal Cord Injury and Enhances Insulin-Like Growth Factor-1 Concentration in the Plasma and the Spinal Cord

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Abstract

Previous studies from our laboratory showed that topical application of growth hormone (GH) induced neuroprotection 5 h after spinal cord injury (SCI) in a rat model. Since nanodelivery of drugs exerts superior neuroprotective effects, a possibility exists that nanodelivery of GH will induce long-term neuroprotection after a focal SCI. SCI induces GH deficiency that is coupled with insulin-like growth factor-1 (IGF-1) reduction in the plasma. Thus, an exogenous supplement of GH in SCI may enhance the IGF-1 levels in the cord and induce neuroprotection. In the present investigation, we delivered TiO2-nanowired growth hormone (NWGH) after a longitudinal incision of the right dorsal horn at the T10–11 segments in anesthetized rats and compared the results with normal GH therapy on IGF-1 and GH contents in the plasma and in the cord in relation to blood-spinal cord barrier (BSCB) disruption, edema formation, and neuronal injuries. Our results showed a progressive decline in IGF-1 and GH contents in the plasma and the T9 and T12 segments of the cord 12 and 24 h after SCI. Marked increase in the BSCB breakdown, as revealed by extravasation of Evans blue and radioiodine, was seen at these time points after SCI in association with edema and neuronal injuries. Administration of NWGH markedly enhanced the IGF-1 levels and GH contents in plasma and cord after SCI, whereas normal GH was unable to enhance IGF-1 or GH levels 12 or 24 h after SCI. Interestingly, NWGH was also able to reduce BSCB disruption, edema formation, and neuronal injuries after trauma. On the other hand, normal GH was ineffective on these parameters at all time points examined. Taken together, our results are the first to demonstrate that NWGH is quite effective in enhancing IGF-1 and GH levels in the cord and plasma that may be crucial in reducing pathophysiology of SCI.

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Acknowledgments

This investigation is supported by grants from the Air Force Office of Scientific Research (EOARD, London, UK), and Air Force Material Command, USAF, under grant number FA8655-05-1-3065; Swedish Medical Research Council (Nr 2710-HSS), Swedish Strategic Research Foundation, Stockholm, Sweden; Göran Gustafsson Foundation, Stockholm, Sweden (HSS), Astra Zeneca, Mölndal, Sweden (HSS/AS); The Foundation of the Society for the Study of Neuroprotection and Neuroplasticity, Romania; The Foundation of the Society for the Study of Nanoneurosciences and Neuroregeneration, Romania; The University Grants Commission, New Delhi, India (HSS/AS); Ministry of Science & Technology, Govt. of India & Govt. of Sweden (HSS/AS); Indian Medical Research Council, New Delhi, India (HSS/AS); India-EU Research Co-operation Program (RP/AS/HSS) and IT 794/13 (JVL); Government of Basque Country and UFI 11/32 (JVL); and University of Basque Country, Spain.

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Authors and Affiliations

  1. “RoNeuro” Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania

    Dafin F. Muresanu

  2. Department of Clinical Neurosciences, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania

    Dafin F. Muresanu

  3. Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, University Hospital, Uppsala University, SE-75185, Uppsala, Sweden

    Aruna Sharma & Hari S. Sharma

  4. LaNCE, Department Neurosciences, University of Basque Country, Bilbao, Spain

    José V. Lafuente & Hari S. Sharma

  5. Indian Institute of Technology, School of Biomedical Engineering, Department of Biomaterials, Banaras Hindu University, Varanasi, 221005, India

    Ranjana Patnaik

  6. Department Chemistry & Biochemistry, University of Arkansas, Fayetteville, AR, USA

    Z. Ryan Tian

  7. Department of Pharmaceutical Biosciences, Biological Research on Drug Dependence, Biomedical Center, Uppsala University, Uppsala, Sweden

    Fred Nyberg

  8. Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago, Chile

    José V. Lafuente

  9. International Experimental Central nervous System (CNS) Injury & Repair (IECNSIR), Uppsala University Hospital, Frödingsgatan 12, SE-75421, Uppsala, Sweden

    Aruna Sharma & Hari S. Sharma

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  1. Dafin F. Muresanu
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Correspondence to Hari S. Sharma.

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Muresanu, D.F., Sharma, A., Lafuente, J.V. et al. Nanowired Delivery of Growth Hormone Attenuates Pathophysiology of Spinal Cord Injury and Enhances Insulin-Like Growth Factor-1 Concentration in the Plasma and the Spinal Cord. Mol Neurobiol 52, 837–845 (2015). https://doi.org/10.1007/s12035-015-9298-8

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