The fate of neurons after traumatic spinal cord injury in rats: A systematic review

Iranian Journal of Basic Medical Sciences, 2018 · DOI: 10.22038/IJBMS.2018.24239.6052 · Published: June 1, 2018

Simple Explanation

Traumatic spinal cord injury (TSCI) has a devastating effect on the patient’s quality of life, family, and society. Current clinical therapies attempt to prevent progression of secondary injuries that initiate after acute mechanical insult. New therapeutic approaches, such as cell therapies, gene therapies, and tissue engineering have been proposed to compensate neuronal loss and inhibitory environment of the injured tissue. Detailed understanding of the time-dependent pathophysiological events after TSCI in animal studies may help scientists to accurately decide the time and type of intervention.

Study Duration

Not specified

Participants

49 animal studies

Evidence Level

Systematic Review

Key Findings

1
Both necrotic and apoptotic neuronal deaths occur after TSCI, though necrosis is the prominent mechanism.
2
There are differences in the responses of intrinsic neurons of the spinal cord to the TSCI.
3
The extent of neuronal death in the supraspinal neurons depends on the anatomical location of their axons.

Research Summary

The present study was designed to comprehensively review evidence from animal studies discussing the fate of neurons after TSCI in rats. In the current study, we found that different populations of neurons differently survive the TSCI, and neuronal loss occurs through both mechanisms of apoptosis and necrosis. Various factors are found in this systematic review which affect the extent of neuronal death after TSCI including the type of injury model, severity of injury, the proximity of the injury site to the cell body, and the anatomical location of the supraspinal tracts.

Practical Implications

Therapeutic Time Window

The first 2 weeks post-injury represent a critical time window for therapies aimed at reducing apoptotic neuronal death.

Targeted Cell Therapies

Cell transplantation and neurotrophic factor delivery to the brain stem/brain after TSCI may be a promising intervention.

Personalized Treatment

Selection of the injury model and time of intervention has a crucial role in the efficacy of therapy to preserve spared neurons.

Study Limitations

1
Identification of the mode of cell loss as apoptotic rather than necrotic relies on several morphological and biochemical criteria.
2
In vivo evaluation of cells undergoing apoptosis is intricate, as the phagocytosis of apoptotic cells and their fragments (apoptotic bodies) by activated microglia/macrophages, with subsequent lysosomal degradation, occurs almost immediately after their formation.
3
The other problem with detection of apoptosis using the TUNEL is that the preservation methods to prepare the tissue sections can affect the detection of free DNA strand ends.

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