High‑Throughput Screening Assay Identifies Berberine and Mubritinib as Neuroprotection Drugs for Spinal Cord Injury via Blood‑Spinal Cord Barrier Protection

Neurotherapeutics, 2022 · DOI: 10.1007/s13311-022-01310-y · Published: September 30, 2022

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

The breakdown of the blood–brain spinal cord barrier (BBSCB) worsens central nervous system (CNS) diseases, especially spinal cord injury (SCI). Effective drugs that protect BBSCB function have yet to be developed. This study developed a high-throughput screening assay (HTSA) to identify candidate drugs to protect BBSCB function and examined the therapeutic effects of candidate drugs on SCI. Screening of 1,570 existing drugs identified berberine and mubritinib as potential drugs; both drugs protected BBSCB function and injured tissue, and promoted functional recovery after SCI.

Study Duration

8 Weeks

Participants

Mice and Rats (1,570 existing drugs were screened)

Evidence Level

Not specified

Key Findings

1
Berberine and mubritinib protected BBSCB from oxygen–glucose deprivation and reoxygenation stress in vitro.
2
Berberine and mubritinib reduced BBSCB breakdown 1 day after cervical SCI in mice.
3
Berberine and mubritinib reduced neuronal loss and improved gait performance 8 weeks after SCI.

Research Summary

The study developed a high-throughput screening assay (HTSA) to identify drugs protecting the blood-brain spinal cord barrier (BBSCB). Screening 1,570 drugs identified berberine and mubritinib as candidates. These drugs protected BBSCB function in vitro and in vivo in spinal cord injury (SCI) models. Berberine and mubritinib attenuated neural tissue damage and promoted functional recovery after SCI, indicating their neuroprotective effects by minimizing BBSCB disruption.

Practical Implications

Drug Repurposing

Berberine and Mubritinib, already existing drugs, can be repurposed for neuroprotection in SCI.

HTSA Tool

The developed HTSA can be used to identify other potential neuroprotective drugs.

BBSCB Protection

Protecting the BBSCB is a viable therapeutic strategy for SCI and potentially other CNS diseases.

Study Limitations

1
The precise molecular mechanisms underlying the BBSCB breakdown have yet to be elucidated
2
The TBI model used was aimed at evaluating BBSCB breakdown but not for functional analysis
3
The unknown molecular action of mubritinib appears to contribute to protection of BBSCB.

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