Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

J Comp Neurol, 2012 · DOI: 10.1002/cne.23156 · Published: October 15, 2012

Simple Explanation

This study investigates how specific sugar molecules, called sulfated glycosaminoglycans (GAGs), change in the brain after a traumatic brain injury (TBI) in mice. These sugar molecules are attached to proteins and play a role in how nerve cells grow and repair themselves. The researchers found that after a TBI, there was an increase in a specific type of sulfated GAG, called 4-sulfated CS-GAG, around the injured area. This increase seemed to create a barrier that prevented nerve cells from growing into the damaged tissue. Additionally, they observed a decrease in certain structures called perineuronal nets, which are involved in brain plasticity. These findings suggest that the brain responds to TBI by both inhibiting nerve cell growth in the immediate injury area and promoting plasticity in the surrounding regions.

Study Duration

28 days

Participants

66 male mice (C57BL/6)

Evidence Level

Not specified

Key Findings

1
TBI resulted in an increase in the CSPGs neurocan and NG2 expression in a tight band surrounding the injury core, which overlapped with the presence of 4-sulfated CS GAGs but not with 6-sulfated GAGs.
2
TBI also caused a decrease in the expression of aggrecan and phosphacan in the pericontusional cortex with a concomitant reduction in the number of perineuronal nets.
3
The increased 4S GAG expression in the tight band surrounding injury core serves to separate the core from the axons of spared neurons.

Research Summary

This report describes an increase in sulfated CS-GAG expression in the injury core and in a tight band surrounding it, and a decrease in the number of PNNs and the level of aggrecan and phosphacan in PNNs in the pericontusion region. Immunolabeling analysis with antibodies specific for GAG chain sulfation demonstrated that the increased GAG observed in the injury core and the tight band around the core is primarily the 4-sulfated form of CS-GAG. Altogether, the dual changes in the expression of CSPGs observed in this study following TBI may reflect an endogenous process of repair after an insult to the head where increased CS-GAG in the vicinity of the injury core acts as a barrier, limiting the entry of axons from surviving neurons near the contusion area into the damaged tissue, while the decreased CSPGs in the PNN in the pericontusion cortex may permit a localized increase in plasticity to facilitate regrowth of injured processes.

Practical Implications

Understanding TBI Repair Mechanisms

The study sheds light on the complex molecular responses following TBI, particularly the roles of CSPGs and sulfated GAGs in either promoting or inhibiting nerve regeneration.

Targeted Therapeutic Strategies

The finding that 4S CS-GAG acts as a barrier to axon growth suggests potential therapeutic strategies to modulate GAG sulfation patterns and promote regeneration after TBI.

Promoting Plasticity and Recovery

The observed decrease in PNNs indicates a window of opportunity for therapeutic interventions aimed at promoting neural plasticity and functional recovery in the pericontusion region.

Study Limitations

1
The study is limited to a mouse model of controlled cortical impact injury, and the findings may not be directly translatable to human TBI.
2
The exact mechanisms by which 4S CS-GAG inhibits axon growth and the specific cellular sources of CSPGs in the injured brain require further investigation.
3
The functional consequences of the observed changes in CSPGs and PNNs on long-term recovery and behavioral outcomes were not directly assessed in this study.

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