Over-activation of TRPM2 ion channel accelerates blood-spinal cord barrier destruction in diabetes combined with spinal cord injury rat

International Journal of Biological Sciences, 2023 · DOI: 10.7150/ijbs.80672 · Published: May 8, 2023

Spinal Cord Injury Endocrinology Neurology

Simple Explanation

Spinal cord injury (SCI) is a devastating neurological disorder that often results in loss of motor and sensory function. Diabetes facilitates the blood-spinal cord barrier (BSCB) destruction and aggravates SCI recovery. This study focused on transient receptor potential melastatin 2 (TRPM2) channel and investigated its regulatory role on integrity and function of BSCB in diabetes combined with SCI rat. The results confirmed that diabetes is obviously not conductive to SCI recovery through accelerates BSCB destruction. The mechanistic study demonstrated that under diabetic condition, TRPM2 mediates Ca2+ influx to activate calcium/calmodulin-dependent protein kinase (CaMKII)/eNOS in spinal cord after SCI, which in turn produces ROS production. Consequently, over-activation of TRPM2 ion channel results in excessive apoptosis and weaker angiogenesis during SCI recovery.

Study Duration

Not specified

Participants

160 healthy 8-week-old female Sprague-Dawley rats (200-250g)

Evidence Level

Level: Not specified, Study type: Animal Model

Key Findings

1
Diabetes significantly worsens mitochondrial dysfunction and induces excessive apoptosis of ECs in spinal cord from SCI rat.
2
Diabetes impedes neovascularization in spinal cord from SCI rat with decreases of VEGF and ANG1.
3
Diabetes significantly increases the expression level of TRPM2 in ECs after SCI.

Research Summary

This study confirmed that diabetes significantly aggravates SCI and is not conducive to the repair of BSCB integrity. The study revealed that diabetes will mediate Ca2+ influx by inducing the over-expression of TRPM2 in ECs and activating TRPM2 ion channel. TRPM2 inhibition partially restores BSCB integrity in spinal cord from diabetes combined with SCI rat, indicated that TRPM2 is the key target for diabetes exacerbating BSCB destruction.

Practical Implications

Therapeutic Target

TRPM2 channel may be a key target for the treatment of diabetes combined with SCI.

Drug Development

TRPM2 inhibitors can be explored as potential drugs to ameliorate BSCB destruction and improve SCI recovery in diabetic patients.

Clinical Management

Monitoring TRPM2 expression levels in diabetic SCI patients could help assess BSCB integrity and predict recovery outcomes.

Study Limitations

1
The study used a T1D rat model, which may not fully reflect the complexities of T2D in humans.
2
The study focused on TRPM2, but other ion channels may also play a role in BSCB destruction.
3
The duration of hyperglycemia on nerve cells in spinal cord was 2 weeks, which may be far from the directly affecting neurological function.

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