Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms.

Anam Anjum,Ohnmar Htwe@ Rashidah Ismail,Jalilah Idris,Muhammad Fauzi Daud,Amaramalar Selvi Naicker,Angela Min Hwei Ng,Muhammad Da’In Yazid,Ramesh Kumar Athi Kumar,Yogeswaran Lokanathan

doi:10.3390/ijms21207533

Abstract

Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Its pathophysiology comprises acute and chronic phases and incorporates a cascade of destructive events such as ischemia, oxidative stress, inflammatory events, apoptotic pathways and locomotor dysfunctions. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Efforts have also been devoted in developing neuroprotective and neuro-regenerative therapies that promote neuronal recovery and outcome. Although varying degrees of success have been achieved, curative accomplishment is still elusive probably due to the complex healing and protective mechanisms involved. Thus, current understanding in this area must be assessed to formulate appropriate treatment modalities to improve SCI recovery. This review aims to promote the understanding of SCI pathophysiology, interrelated or interlinked multimolecular interactions and various methods of neuronal recovery i.e., neuroprotective, immunomodulatory and neuro-regenerative pathways and relevant approaches.

Highlights

Spinal cord injury (SCI) is a devastating neurological state producing physical dependency, morbidity, psychological stress and financial burden
SCI is associated with autonomic dysreflexia (AD) occurring in 48%–60% of cases at above thoracic 6th vertebral level (T6) and involving a sudden onset of excessively high blood pressure [4]
The first problem is how to prevent the cascade of events which is associated with the secondary spinal injury phase

Summary

Introduction

Spinal cord injury (SCI) is a devastating neurological state producing physical dependency, morbidity, psychological stress and financial burden. Available treatments are limited and only provide supportive relief to patients with lifetime disability [1]. Heterogeneous factors such as complex characteristics, abundant inconsistencies and complex pathophysiologic consequences post-SCI are the major reasons for poor understanding and failure of SCI treatment. Despite numerous studies and availability of various regenerative treatment strategies, post-SCI recovery remains controversial, and scientists are still exploring methods that could prevent or reverse the devastating outcomes of SCI [2]. This review highlights recent findings and critical knowledge gaps about fundamental pathophysiology following SCI, multicellular and multimolecular interactions, phases and underlying recovery mechanisms of SCI, especially those targeting neuroprotection, immuno-modulatory and neuro-regenerative pathways. Strategies to re-establish the lost connectivity between spinal cord cells and their interactions are explored

Objectives

Discussion

Conclusion