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Early 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 neuroprotection

  • Basic Neurosciences, Genetics and Immunology - Review article
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Abstract

Spinal cord injury (SCI) is a devastating disease that leads to permanent disability of victims for which no suitable therapeutic intervention has been achieved so far. Thus, exploration of novel therapeutic agents and nano-drug delivery to enhance neuroprotection after SCI is the need of the hour. Previous research on SCI is largely focused to improve neurological manifestations of the disease while ignoring spinal cord pathological changes. Recent studies from our laboratory have shown that pathological recovery of SCI appears to be well correlated with the improvement of sensory motor functions. Thus, efforts should be made to reduce or minimize spinal cord cell pathology to achieve functional and cellular recovery to enhance the quality of lives of the victims. While treating spinal cord disease, recovery of both neuronal and non-neuronal cells, e.g., endothelia and glial cells are also necessary to maintain a healthy spinal cord function after trauma. This review focuses effects of novel therapeutic strategies on the role of spinal cord microvascular reactions and endothelia cell functions, i.e., blood–spinal cord barrier (BSCB) in SCI and repair mechanisms. Thus, new therapeutic approach to minimize spinal cord pathology after trauma using antibodies to various neurotransmitters and/or drug delivery to the cord directly by topical application to maintain strong localized effects on the injured cells are discussed. In addition, the use of nanowired drugs to affect remote areas of the cord after their application on the injured spinal cord in thwarting the injury process rapidly and to enhance the neuroprotective effects of the parent compounds are also described in the light of current knowledge and our own investigations. It appears that local treatment with new therapeutic agents and nanowired drugs after SCI are needed to enhance neurorepair leading to improved spinal cord cellular functions and the sensory motor performances.

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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 research on SCI is supported by grants from Swedish Medical research Council nr 2710, Göran Gustafsson Foundation, Stockholm, Sweden, Astra-Zeneca, Mölndal, Sweden, Acure Pharma, Uppsala, Sweden; Alexander von Humboldt Foundation, Bonn, Germany, IPSEN Beufour, Paris, France; Department of Science and Technology, Govt. of India, University Grants Commission, New Delhi, India and Indian Medical Research Council, New Delhi, India. I am indebted to Professor Erik V Stålberg, Dr Tomas Winkler, Department of Clinical Neurophysiology, Uppsala University Hospital; Professor R D Badgaiyan, Massachusetts General Hospital, Harvard University, Boston, MA, USA; Dr Syed F Ali, Division of Neurotoxicology, National Centre for Toxicological research, Food and Drug Administration, US/FDA, Jefferson, USA and Professor Byron Kakulas, University of Western Perth, Queen Elizabeth Hospital, Perth, Western Australia for providing me important advice and suggestion throughout this work and critically reading the manuscript. Secretarial assistance of Aruna Sharma and Angela Ludwig is highly appreciated.

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  1. Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, 75185, Uppsala, Sweden

    Hari Shanker Sharma

  2. Frödingsgatan 12: 1228, 75421, Uppsala, Sweden

    Hari Shanker Sharma

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Sharma, H.S. Early 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 neuroprotection. J Neural Transm 118, 155–176 (2011). https://doi.org/10.1007/s00702-010-0514-4

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