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

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.

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

“…Endothelial cells, basement membranes, pericytes, and astrocytic end-feet processes constitute a specialized system for this functional barrier [5]. Early microvascular reactions and BSCB disruption are instrumental in the pathophysiology of SCI and repair [6,7].…”

Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice

“…Previous studies focused largely on alleviating neurological manifestations of the injury while ignoring pathological changes in the spinal cord (3). The compression forces induced by SCI can rupture blood vessels, destroy endothelial cells and pericytes, disrupt the BSCB, and cause production of numerous molecules that result in vascular disruption (4,5).…”

Changes in substance P and NK1 receptor immunohistochemistry following human spinal cord injury

“…3 Such rostrocaudal spreading of edema results in further tissue damage and worsened functional outcome. 4 Moreover, a study by Koyanagi et al 5 demonstrated that surgical decompression did not affect cord swelling. Thus, edema following SCI presents as a serious complication, with no effective treatment currently available.…”