Traumatic Spinal Cord Injury - Overview Of Its Mechanism And Modeling Approach
Traumatic spinal cord injury is a crippling neurological disorder that has a significant financial effect on afflicted people and the healthcare system.
Katharine TateJan 09, 202379 Shares1786 Views
Traumatic spinal cord injuryis a crippling neurological disorder that has a significant financial effect on afflicted people and the healthcare system.
According to this articlefrom Spinal-Injury.net, a person can suffer from spinal trauma if they sustain an injury that causes damage to their spinal cord, spinal column, or the bones that surround their spinal cord. Damage to the spinal cord, which includes the nerves that convey information between the brain and the rest of the body, can produce permanent changes in the functions of the body.
In North America, 12,500 new incidences of spinal cord injury are reported each year.
More than 90% of spinal cord injury instances are traumatic and result from traffic accidents, violence, sports, or falls.
Spinal cord injury has a documented male-to-female ratio of 2:1, and it occurs more commonly in adults than children.
The age distribution is bimodal, with a first peak of young people and the second high of those over 60.
The damage and retained functions significantly impact the life expectancy of traumatic spinal cord injury patients.
Cervical, thoracic, lumbar, and sacral spinal cord injuries are the four types.
The spinal cord is encircled by bone rings known as vertebrae. The spinal column is made up of these bones.
The higher the lesion occurs in the spinal column, the more dysfunction a person would feel. The vertebrae are called from their placement.
The cervical vertebrae are the seven vertebrae in the neck. C-1 is the top vertebra, C-2 is the next, and so on.
Injury to the cervical spinal cord generally results in loss of function in the arms and legs, leading in quadriplegia and spinal cord paralysis.
The thoracic vertebrae are the 12 vertebrae in the thorax. T-1 is the first thoracic vertebra to which the top rib connects.
Thoracic spinal cord injuries often affect the chest and legs, resulting in paraplegia. The lumbar vertebra is the vertebra in the lower back between the thoracic vertebra, where the ribs join, and the pelvis (hip bone).
The sacral vertebrae are located from the pelvis to the end of the spinal column. Injuries to the five lumbar vertebrae (L-1 through L-5) and the five sacral vertebrae (S-1 through S-5) often result in some loss of function in the hips and legs.
The secondary injury develops within minutes of the first injury and may linger for weeks or months, causing progressive damage to the spinal cord tissue around the lesion site.
It was observed during a study on spinal cord damage in dogs that eliminating the post-traumatic hematomyelia improved neurological prognosis.
More spinal cord damage is caused by the presence of "biochemical components" in the necrotic hemorrhagic lesion.
Secondary injury is still used in the field to define cellular, molecular, and biochemical activities that continue to self-destruct spinal cord tissue and impede neurological recovery after spinal cord damage.
There are three types of secondary injury: acute, subacute, and chronic.
The initial phase of spinal cord injury includes vascular damage, ionic imbalance, neurotransmitter accumulation (excitotoxicity), free radical generation, calcium influx, lipid peroxidation, inflammation, edema, and necrotic cell death: apoptosis, demyelination of surviving axons.
The acute secondary damage components listed below contribute to the pathophysiology of spinal cord injury.
Visual description of injury in a human spinal cord
One of the early outcomes of initial damage is disruption of spinal cord arterial supply and hypo-perfusion.
Hypovolemia and hemodynamic shock caused by severe bleeding and neurogenic shock limit spinal cord perfusion and ischemia in spinal cord injury patients.
Larger arteries, such as the anterior spinal artery, usually stay intact, but rupture of smaller intramedullary vessels and capillaries sensitive to severe injury results in leukocyte and red blood cell extravasation.
Blood flow to the spinal cord is further disrupted by increased tissue pressure in the edematous damaged spinal cord and hemorrhage-induced vasospasm in intact arteries.
In rat and monkey models of spinal cord injury, blood flow at the lesion epicenter decreases gradually during the first several hours after damage.
It stays low for up to 24 hours.
Gray matter is more vulnerable to ischemia injury than white matter because it comprises neurons with high metabolic requirements and has a 5-fold greater density of capillary beds.
After the damage, white matter blood flow often recovers to normal within 15 minutes; however, the gray matter has many hemorrhages and, consequently, re-perfusion usually does not occur for the first 24 hours.
Vascular injury, bleeding, and ischemia eventually result in cell death and tissue damage through various processes, including oxygen deprivation, ATP loss, excitotoxicity, ionic imbalance, free radical production, and necrotic cell death.
Glutamate is the principal excitatory neurotransmitter in the central nervous system (CNS).
Glutamate binds to ionotropic (NMDA, AMPA, and Kainate receptors) and metabotropic receptors, resulting in calcium influx inside cells.
When intracellular Ca2+ levels grow, astrocytes may also expel excess glutamate extracellularly. Mitochondria have an essential role in calcium-dependent neuronal death.
During glutamate-induced excitotoxicity, NMDA receptor overactivity promotes mitochondrial calcium overflow in neurons. Ca2+ is transported into the mitochondria via the mitochondrial calcium uniporter (MCU).
Shortly after spinal cord damage, an influx of Ca2+ activates many protein kinases and phospholipases.
Riluzole, a Na+ channel blocker, lowers tissue damage and improves functional recovery in spinal cord injury, emphasizing the importance of sodium in secondary injury processes.
An increase in Na+ concentration activates the Na+/H+ exchanger, increasing intracellular H+. Lipid and protein oxidation is one of the critical secondary damage mechanisms after spinal cord injury.
Lipid and protein oxidation after spinal cord damage has several severe biological consequences.
These include mitochondrial respiratory and metabolic failure and DNA alterations leading to cell death.
Cell death is a significant event in the secondary damage processes that affect neurons and glia after spinal cord injury.
Necrosis and apoptosis were the first two main cell death mechanisms identified.
Necroptosis and autophagy are two novel kinds of cell death discovered in recent research.
Receptors control the process of necroptosis. It is triggered by TNF receptor 1 (TNFR1) and requires RIPK1 and RIPK3.
In rats, apoptosis begins as early as 4 hours after injury and peaks at 7 days. Injury-induced Ca2+ influx is the primary cause of apoptosis, which activates caspases and calpain, enzymes involved in protein breakdown.
Human post-mortem studies revealed that Fas-mediated cell death is associated with oligodendrocyte apoptosis and the inflammatory response after spinal cord damage.
Dysregulation of autophagy results in neuronal death, and blocking it has been related to neurodegenerative diseases such as Parkinson's and Alzheimer's.
Autophagy aids cell survival by eliminating toxic proteins and mitochondrial damage.
Glial scarring is a multifactorial phenomenon generated by several populations in the injured spinal cord.
Both resident and invading inflammatory cells have a role in glial activation and scar formation.
Fibroblasts, pericytes, and ependymal cells, as well as glial and immune cells, contribute to its formation.
Activated astrocytes play an essential role in the formation of the glial scar. Blood-brain-barrier regeneration also requires reactive astrogliosis.
Leukocyte infiltration, cell death, myelin breakdown, and functional recovery are all impeded by blocking this pathway.
Chondroitin sulfate proteoglycans (CSPGs) are well known for inhibiting axonal regeneration by the glial scar.
CSPGs are substantially elevated after injury and reach a peak of expression two weeks later. After spinal cord damage, the inhibitory effects of the astrocytic glial scar on axonal regeneration have recently been called into doubt.
Sofroniew and colleagues revealed that spontaneous axon regrowth did not occur after scar ablation or prevention using various transgenic mouse models.
Visual description of a man with highlighted spinal cord along with two spinal cords on his sides
Unfortunately, there is no method to repair spinal cord injury. However, researchers are constantly developing novel therapies, including prostheses and drugs, that may accelerate nerve cell regeneration or enhance the function of the nerves that survive a spinal cord injury.
A spinal cord injury is one of a person's most devastating ailments. This form of physical damage may cause paraplegia, the inability to move the lower body, quadriplegia, or the inability to move the body.