3.3. Glial-associated damage

In SCI, damage to the myelin sheet that is demyelination causes the exposure of axons to the harmful surroundings that lead to necrosis or apoptosis of overall neurons [9]. Moreover, the process of demyelination delays or blocks signal conduction via axons that leads to ineffective communication between neurons. This process of demyelination is a result of damages to the oligodendrocytes that were generated by glutamate excitotoxicity [16]. Later on, an inflammatory reaction regresses, which is followed by a formation of glial scars. In the initial stages of SCI, astrocytes proliferate at the damaged site to form glial scars, which separate neural tissue to decline neuroinflammation in early phases. Cells in this scar region secrete inhibitory molecules, which inhibit functional recovery [17].

mechanisms that support the struggle of tissue survival after SCI include higher expression of proteases and stress proteins and lower expression of cytoskeletal and synapsis-based messen-

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At the initial stage of SCI, different cellular factors such as nuclear factor kappa B (NF-κB) and 70 kD heat shock protein (HSP-70) get activated that last for 24 hours. A stimulation of NF-κB facilitates more expression of genes to moderate regeneration or apoptosis [24]. Moreover, an increased level of HSP-70 with metallothioneins 1 & 2 protects the cells from oxidative stress. An activation of catalase, superoxide dismutases and glutathione peroxidase occurs in later

During an early phase after SCI, interleukins (IL-6, IL-1β), cyclooxygenase (COX)-2 and TNF-α are activated, which get to normal stage again after 2 weeks. Integrins, vascular and intercellular CAMs, selectins and cadherins are upregulated in early phase of SCI [25]. Inflammatory genes are expressed in several spinal cord cells, which are predominantly studied in microglia. The interleukins IL-6, IL-1β and chemokine ligands, such as 2/M1P2α and 2/MCP-1, help in bringing different immune cells to the injured area [14]. After 3–7 days, microglial gene expression that includes genes, such as MRF-1 (microglial response factor-1), cathepsin, galectin-3, CYBA (cytochrome b-245, alpha polypeptide), CASP1 (caspase 1), MAPK14 (mitogenactivated protein kinase 14), CCND1 (cyclin D1) and leukocyte surface antigen CD53/OX44, contributes in immune response, phagocytosis and cell death. Furthermore, other genes such as the classical complement pathway, which related to phagocytosis, showed an insistent

A great number of genes that encode specific proteins for calcium, sodium and potassium pumps, synapsis and cell excitability show a major decrease in the first week following SCI [26]. This reduction reflects alterations of gene profile in neurons and the progress of apoptosis that occurs after SCI. Late axonal regeneration after SCIs is accompanied by overexpression of CORO1B (Coronin, actin binding protein, 1B), RAB13 (Rab13, member RAS oncogene family), NINJ (Ninjurin), ANK (Ankyrin), cAMP-related genes and myelin oligodendrocyte glycopro-

The upregulation of cell cycle genes, including cyclins, c-Myc (V-myc avian myelocytomatosis viral oncogene homolog) and GADD45A (growth arrest and DNA damage-inducible, alpha), is being reported after 24 hours of SCI [27]. Once these genes are activated, it induces apoptosis and astrocytic proliferation through formation of the glial scar [27]. In the initial stages of SCI, upregulation of associated genes, such as BAX (BCL2-associated X protein),

ger RNA [14]. Following are the molecular alterations after SCI.

4.1. Stress and transcription response

stages [25].

4.2. Inflammatory reaction

upregulation after SCI [25].

4.3. Neuron-related genes

tein [27].

4.4. Cell cycle genes
