A review of published reports on neuroprotection in spinal cord injury

Abstract

Study design: Literature review. Objectives: To review the main published current neuroprotection research trends and results in spinal cord injury (SCI). Setting: This paper is the result of a collaboration between a group of European scientists. Methods: Recent studies, especially in genetic, immune, histochemical and bio (nano)-technological fields, have provided new insight into the cellular and molecular mechanisms occurring within the central nervous system (NS), including SCIs. As a consequence, a new spectrum of therapies aiming to antagonize the 'secondary injury' pathways (that is, to provide neuroprotection) and also to repair such classically irreparable structures is emerging. We reviewed the most significant published works related to such novel, but not yet entirely validated, clinical practice therapies. Results: There have been identified many molecules, primarily expressed by heterogenous glial and neural subpopulations of cells, which are directly or indirectly critical for tissue damaging/sparing/ re-growth inhibiting, angiogenesis and neural plasticity, and also various substances/energy vectors with regenerative properties, such as MAG (myelin-associated glycoprotein), Omgp (oligodendrocyte myelin glycoprotein), KDI (synthetic: Lysine-Asparagine-Isoleucine 'g-1 of Laminin Kainat Domain'), Nogo (Neurite outgrowth inhibitor), NgR (Nogo protein Receptor), the Rho signaling pathway (superfamily of 'Rho-dopsin geneFincluding neurotransmitterFreceptors'), EphA4 (Ephrine), GFAP (Glial Fibrillary Acidic Protein), different subtypes of serotonergic and glutamatergic receptors, antigens, antibodies, immune modulators, adhesion molecules, scavengers, neurotrophic factors, enzymes, hormones, collagen scar inhibitors, remyelinating agents and neurogenetic/plasticity inducers, all aiming to preserve/re-establish the morphology and functional connections across the lesion site. Accordingly, modern research and experimental SCI therapies focus on several intricate, rather overlapping, therapeutic objectives and means, such as neuroprotective, neurotrophic, neurorestorative, neuroreparative, neuroregenerative, neuro(re)constructive and neurogenetic interventions. Conclusion: The first three of these therapeutical directions are generically assimilated as neuroprotective, and are synthetically presented and commented in this paper in an attempt to conceptually systematize them; thus, the aim of this article is, by emphasizing the state-of-the art in the domain, to optimize theoretical support in selecting the most effective pharmacological and physical interventions for preventing, as much as possible, paralysis, and for maximizing recovery chances after SCI.

The glial scar in spinal cord injury and repair

“…However, the clinical translation of ChABC may be set back by two major challenges: (1) its poor thermostability and (2) its synthesis from an Escherichia coli origin, which may carry immunological risk [114,115] . in addition to ChABC, there is evidence that MMPs can degrade the protein backbone of some CSPGs to restrict the formation of a glial scar [116] , and the process is associated with mitigation of a functional deficit; however, axonal dieback is an unpleasant secondary response [117] .…”

“…it is well-established that chondroitinase ABC (ChABC) significantly ameliorates the hostile-matrix microenvironment following SCI by enzymatically digesting the glycosaminoglycan side-chains of CSPGs and promotes functional recovery [4,111,112] . in accord with these findings, a recent study showed that the infusion of ChABC is also successful in restoring neuronal glycosylation to normal [113] .However, the clinical translation of ChABC may be set back by two major challenges: (1) its poor thermostability and (2) its synthesis from an Escherichia coli origin, which may carry immunological risk [114,115] . in addition to ChABC, there is evidence that MMPs can degrade the protein backbone of some CSPGs to restrict the formation of a glial scar [116] , and the process is associated with mitigation of a functional deficit; however, axonal dieback is an unpleasant secondary response [117] .…”

Evolution of traumatic spinal cord injury in patients with ankylosing spondylitis, in a Romanian rehabilitation clinic

“…Regarding the primary lesions pathways and topographic-related issues, 'the critical velocity of tissue movement, which will lead to an axonal tear in a spinal cord contusion, is 0.5-1 m s − 1 , concentrating most of the stretching and shearing forces in the central part'. 29,30 MRI control 31 was mandatory in patient no. 5, with a symptomfree interval followed by neurological deterioration, and in patients no.…”

Neural plasticity and functional recovery of human central nervous system with special reference to spinal cord injury

“…[21][22][23] Despite the tremendous efforts made, scientists have failed to fully understand the secondary destructive process and all protection measures have not succeeded in preventing it from progressing. 21 The use of mega dose of methylprednisolone recommended by the NASCAS II and III studies have Figure 3 The hippocampus and amygdala of the limbic system (courtesy of http://pubs.niaaa.nih.gov/publications/arh284/images/ tapert.gif).…”