Understanding Molecular Pathology along Injured Spinal Cord Axis: Moving Frontiers toward Effective Neuroprotection and Regeneration

Abstract

Spinal cord injury (SCI) is a severe, often life threatening, traumatic condition leading to serious neurological dysfunctions. The pathological hallmarks of SCI include inflammation, reactive gliosis, axonal demyelination, neuronal death, and cyst formation. Although much has been learned about the progression of SCI pathology affecting a large number of biochemical cascades and reactions, the roles of proteins involved in these processes are not well understood. Advances in proteomic technologies have made it possible to examine the spinal cord proteome from healthy and experimental animals and disclose a detailed overview on the spatial and temporal regionalization of these secondary processes. Data clearly demonstrated that neurotrophic molecules dominated in the segment above the central lesion, while the proteins associated with necrotic/apoptotic pathways abound the segment below the lesion. This knowledge is extremely important in finding optimal targets and pathways on which complementary neuroprotective and neuroregenerative approaches should be focused on. In terms of neuroprotection, several active substances and cell-based therapy together with biomaterials releasing bioactive substances showed partial improvement of spinal cord injury. However, one of the major challenges is to select specific therapies that can be combined safely and in the appropriate order to provide the maximum value of each individual treatment.

The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury

“…Although a fundamental understanding has been obtained through various modeling studies, there is still a lack of knowledge about the pathophysiology of SCI. It has been established that everything starts with a primary mechanic traumatism by compression, laceration, distraction, or shearing ( 3 ). This induces vascular lesions that lead to the formation of a hematoma at the lesion site, which itself causes local ischemia, edema, and cell-regulated cell death such as apoptosis ( 3 ).…”

“…It has been established that everything starts with a primary mechanic traumatism by compression, laceration, distraction, or shearing ( 3 ). This induces vascular lesions that lead to the formation of a hematoma at the lesion site, which itself causes local ischemia, edema, and cell-regulated cell death such as apoptosis ( 3 ). Moreover, the blood spinal cord barrier is disrupted, which initiates the secondary extension of the lesion through the attraction of inflammatory cells, the accumulation of cytokines and vasoactive proteins.…”

The Antibody Dependant Neurite Outgrowth Modulation Response (ADNM) involvement in Spinal Cord Injury

“…Although fundamental understanding has been obtained through various modeling studies, there is still a lack of knowledge about the pathophysiology of SCI, but all starts with a primary mechanic traumatism by compression, laceration, distraction or shearing 3 . This induces vascular lesions that lead to the formation of a hematoma on the lesion site, which itself causes a local ischemia, edema, and cell regulated cell death such apopotosis 3 . Moreover, the blood spinal cord barrier is disrupted, which initiates the secondary extension of the lesion by the attraction of in ammatory cells, the accumulation of cytokines and vasoactive proteins.…”

“…Finally, cell death is responsible of accumulation of cellular debris, potassium, ATP, leading to a cytotoxic environment. Then attracting pro-in ammatory M1 microglial cells and phagocytes in ltrate this cytotoxic environment leading to an oxidative stress which is toxic to adjacent neurons 3 . In our laboratory, a previous study, focused on subacute in ammatory response after SCI demonstrated that after 3 days, in ammatory response is intense in lesion and in downstream caudal 1 segment, where high amounts of cytokines and immunoglobulins are detected, and where the Rho-Rock and Memo1-RhoA-Diaph1 pathways are activated 4,5 .On the contrary, more caudally and distally from the central lesion, we have rather detected neurite outgrowth proteins and chemokines attracting rst neutrophils, then T regulatory cells, anti-in ammatory M2 microglial cells, leading to creating a bene cial environment possibilities for neurite outgrowth on both sides of the lesion 4 .…”

The Efficacy of Combined Medication With Methylprednisolone and Erythropoietin in the Treatment of Ischemia-Reperfusion Injury to the Spinal Cord in Patients With Cervical Spondylotic Myelopathy

“…Due to the appearance of soft tissue outside the spinal cord and the compression of the peripheral bone, the function of the spinal nerve deteriorates, and the anatomical structure changes. Cervical spine myelopathy can lead to disorders of the blood supply to the spinal cord and venous reflux, cause myelomalacia and bone marrow necrosis, and lead to spinal nerve malfunction [ 4 , 5 ]. Although surgery may be effective in alleviating the spinal cord compression, it may also cause some degree of ischemia-reperfusion injury, thereby making it difficult to restore the nerve function after decompression [ 6 , 7 ].…”