mGluR5 protect astrocytes from ischemic damage in postnatal CNS white matter

Abstract

Graphical abstract

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

“…During a pathophysiological state, the balance between solute and water influx at the intracellular compartment is disturbed, thereby causing cell swelling and loss of cytoskeletal integrity and promoting cell death [ 11 ]. Ionic oedema occurs due to the increased permeability of the blood–spinal cord barrier that increases trans-endothelial ion transport and causes the loss of ions and water from the interstitial space [ 12 ]. Endothelial injury and inflammation subsequently increase the pore size and thus allow large plasma-derived molecules to pass through the cell membrane, resulting in vasogenic oedema [ 12 ].…”

“…Ionic oedema occurs due to the increased permeability of the blood–spinal cord barrier that increases trans-endothelial ion transport and causes the loss of ions and water from the interstitial space [ 12 ]. Endothelial injury and inflammation subsequently increase the pore size and thus allow large plasma-derived molecules to pass through the cell membrane, resulting in vasogenic oedema [ 12 ]. This acute secondary injury phase continues from 2 h to 48 h. Continuous haemorrhage, oedema and inflammatory stage lead to substantial necrosis indicated by the increased concentration of specific inflammatory and the presence of structural biomarkers, e.g., glial fibrillary acidic protein (GFAP) or IL-6 in cerebrospinal fluid (CSF) [ 6 ].…”

“…This acute secondary injury phase continues from 2 h to 48 h. Continuous haemorrhage, oedema and inflammatory stage lead to substantial necrosis indicated by the increased concentration of specific inflammatory and the presence of structural biomarkers, e.g., glial fibrillary acidic protein (GFAP) or IL-6 in cerebrospinal fluid (CSF) [ 6 ]. These processes provoke free radical formation, glutamate-mediated excitotoxicity and neurotoxicity [ 12 ] ( Figure 1 c).…”

“…Glutamate is an excitatory neurotransmitter that is released in the central nervous system (CNS) and interacts with N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate ionotropic and metabotropic receptors [ 12 ] ( Figure 2 ). The activation of glutamate receptors during SCI greatly increases glutamate concentrations and produces persistent excitotoxicity and cell death [ 12 ].…”

“…Glutamate is an excitatory neurotransmitter that is released in the central nervous system (CNS) and interacts with N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate ionotropic and metabotropic receptors [ 12 ] ( Figure 2 ). The activation of glutamate receptors during SCI greatly increases glutamate concentrations and produces persistent excitotoxicity and cell death [ 12 ]. Abnormal increases in glutamate excitation are caused by diverse events, such as mechanical stress, formation of apoptotic and necrotic cells, failure of Na + /K + ATPase in the axonal membrane, lipid peroxidation and formation of 4-hydroxynonenal [ 5 ].…”