Different Ways to Die: Cell Death Pathways and Their Association With Spinal Cord Injury

Neurospine, 2023 · DOI: https://doi.org/10.14245/ns.2244976.488 · Published: June 1, 2023

Simple Explanation

Cell death is a process where cells lose their normal functions, which can be programmed (to replace old cells) or nonprogrammed (due to injury). It involves multiple pathways and can either maintain the body's balance or cause inflammation and harm. In neurological diseases and spinal cord injuries (SCI), impairments in programmed cell death signaling are observed. SCI disrupts motor activities due to the death of neuronal and glial cells, leading to axonal degeneration. Understanding the molecular basis of cell death pathways may enhance neuronal and glial survival, improving neurological deficits after SCI. This review summarizes programmed and non-programmed cell death pathways in SCI.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
SCI pathophysiology involves blood-spinal cord barrier collapse, immune cell transmigration, and rupture of cellular axons and membranes. Key signaling pathways regulate apoptotic activity in SCI.
2
Several cell death pathways, including apoptosis, autophagy, ferroptosis, and necroptosis, are directly linked to primary and secondary SCI progression.
3
Necrosis, a nonprogrammed cell death triggered by toxins and physical injuries, contributes to neurological impairment, spinal cord tissue loss, and cystic cavitation of the spinal cord.

Research Summary

Cell death pathways play a major role in SCI pathogenesis and progression. Initial tissue injury results in secondary injury, which further damages the spinal tissues chemically and mechanically, causes neuronal excitotoxicity because the calcium level in the cells is too high, and increases reactive oxygen and glutamate levels. Different cell death pathways associated with SCI include programmed apoptotic cell death (apoptosis and anoikis) and programmed nonapoptotic cell death (autophagy, paraptosis, mitoptosis, parthanatos, ferroptosis, pyroptosis, and necroptosis). Nonprogrammed necrosis in SCI contributes to neurological impairment, spinal cord tissue loss, and cystic cavitation of the spinal cord. Understanding the interplay between apoptosis and necrosis is crucial.

Practical Implications

Targeted Therapies

Identifying specific therapeutic targets within cell death pathways may lead to the development of more effective treatments for SCI.

Neuroprotection Strategies

Understanding the roles of various cell death mechanisms can aid in designing neuroprotective drugs to preserve tissue and function after CNS injury.

Clinical Trials

Further research, including clinical trials, is needed to deepen the understanding of cell death processes in SCI and translate findings into clinical improvements.

Study Limitations

1
Many cell death pathways for axonal/neuronal regeneration and proinflammatory signaling-induced secondary injury in SCI are undiscovered.
2
The specific pathways triggering apoptotic death of astrocytes, neurons, microglia, and oligodendroglia following SCI are yet unknown.
3
Adequate research on the role of ferroptosis in SCI still needs to be done.

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