Quantitative analysis of cellular inﬂammation after traumatic spinal cord injury: evidence for a multiphasic inﬂammatory response in the acute to chronic environment

Brain, 2010 · DOI: 10.1093/brain/awp322 · Published: January 19, 2010

Simple Explanation

Traumatic spinal cord injuries disrupt the body's natural barriers, leading to an influx of immune cells that can worsen the initial damage and hinder recovery. This study focuses on understanding how these immune cells behave over both short and long periods after a spinal cord injury. Researchers developed a new method to quickly and accurately track changes in the main types of immune cells in the injured spinal cord using flow cytometry. They monitored these changes daily for the first 10 days and then periodically up to 180 days after the injury. The study revealed that inflammation in the spinal cord occurs in multiple phases. The initial phase involves neutrophils, macrophages/microglia, and T cells, while a later phase, starting after 14 days, involves all three cell types and lasts for up to 180 days after the injury.

Study Duration

180 days

Participants

Female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
The study quantitatively demonstrates a novel time-dependent multiphasic response of cellular inﬂammation in the spinal cord after spinal cord injury.
2
The early phase of cellular inﬂammation is comprised principally of neutrophils (peaking 1 day post-injury), macrophages/microglia (peaking 7 days post-injury) and T cells (peaking 9 days post-injury).
3
Blockade of chemoattractant C5a-mediated inﬂammation after 14 days post-injury reduced locomotor recovery and myelination in the injured spinal cord, suggesting that the late inﬂammatory response serves a reparative function.

Research Summary

This study characterizes a novel cell preparation method that assesses, quickly and effectively, the changes in the principal immune cell types by ﬂow cytometry in the injured spinal cord, daily for the ﬁrst 10 days and periodically up to 180 days after spinal cord injury. These data quantitatively demonstrate a novel time-dependent multiphasic response of cellular inﬂammation in the spinal cord after spinal cord injury and are veriﬁed by quantitative stereology of immunolabelled spinal cord sections at selected time points. Findings from this study demonstrate, for the ﬁrst time, a temporally distinct second phase of cellular inﬂammation in the injured central nervous system and reveal an important multiphasic component of neuroinﬂammation that may be critical for the design and implementation of rational therapeutic treatment strategies.

Practical Implications

Therapeutic interventions

Understanding the multiphasic inflammatory response could lead to more effective treatments for spinal cord injury, including cell-based and pharmacological approaches.

Timing of treatment

The study suggests that the timing of anti-inflammatory treatments is crucial, as blocking inflammation at different phases can have different effects on recovery.

Reparative role of inflammation

The late phase of inflammation may play a reparative role, highlighting the need to consider the potential benefits of inflammation in the chronic phase of spinal cord injury.

Study Limitations

1
The study was conducted on female Sprague Dawley rats, and the results may not be directly applicable to humans or other species.
2
The study focused on specific immune cell types (neutrophils, macrophages/microglia, and T cells), and other immune cells or factors may also play a role in the inflammatory response.
3
Some temporal differences that were statistically signiﬁcant in the ﬂow cytometric data set failed to yield signiﬁcant differences in the stereologic data set.

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