Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity

J Clin Invest, 2023 · DOI: https://doi.org/10.1172/JCI162253 · Published: May 15, 2023

Simple Explanation

Ischemic stroke affects millions each year, often leading to long-term disabilities. Understanding how the brain recovers after a stroke is crucial for developing new treatments. This study focuses on the role of the complement C3a receptor (C3aR) in the recovery process. The C3aR is involved in inflammation and has roles in brain development and plasticity. The research found that C3aR has opposing effects: it inhibits recovery in the early stages after a stroke but helps in the later stages. Treating mice with C3a after a week improved motor function.

Study Duration

Not specified

Participants

Mice lacking C3aR (C3aR–/–) and mice overexpressing C3a in the brain

Evidence Level

Not specified

Key Findings

1
C3aR signaling has opposing effects on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase.
2
Pharmacological treatment with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity.
3
C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex.

Research Summary

The study investigates the role of the C3a/C3aR axis in regulating glial responses in the peri-infarct cortex of mice subjected to ischemic stroke, assessing functional recovery and connectivity changes with intranasal C3a administration. Key findings include the dual role of C3aR in post-stroke recovery, inhibiting early recovery but promoting later improvement, and the positive effects of intranasal C3a treatment on motor function, astrocyte reactivity, and white matter reorganization. The research suggests that delayed initiation of C3a treatment could harness its beneficial effects on astrocytes and neural plasticity without the adverse recruitment of inflammatory cells, offering a potential therapeutic strategy for stroke recovery.

Practical Implications

Therapeutic Timing

Timing of C3a treatment is critical; delayed initiation may maximize benefits while minimizing early negative effects.

Astrocytes as Target

Modulating astrocyte reactivity with C3a shows promise for promoting functional recovery after stroke.

Intranasal Delivery

Intranasal administration of C3a is a feasible method for delivering therapeutic peptides directly to the brain.

Study Limitations

1
The use of only non-aged male mice.
2
Differences in brain size and in the distance from the nasal cavity to the cerebral cortex between mice and humans may limit direct inference of our findings to clinical stroke.
3
Further investigations are needed to determine the relevance of our findings in females and in aged mice.

Your Feedback

Was this summary helpful?

Back to Immunology