Exogenous Basic Fibroblast Growth Factor Inhibits ER Stress–Induced Apoptosis and Improves Recovery from Spinal Cord Injury

CNS Neuroscience & Therapeutics, 2013 · DOI: 10.1111/cns.12013 · Published: January 1, 2013

Simple Explanation

Spinal cord injury (SCI) often leads to permanent disability. This study explores how a protein called basic fibroblast growth factor (bFGF) can help recovery by preventing cell death. The research shows that SCI causes endoplasmic reticulum (ER) stress, which leads to cell death (apoptosis). bFGF can reduce this ER stress and thus prevent apoptosis. The study found that bFGF activates certain signals (PI3K/Akt and ERK1/2) that protect nerve cells and promote recovery after SCI, suggesting bFGF could be a potential treatment for SCI.

Study Duration

7 days

Participants

Young adult female Sprague–Dawley rats (220–250 g)

Evidence Level

Not specified

Key Findings

1
ER stress-induced apoptosis is involved in the early stages of spinal cord injury in rats, indicated by increased levels of GRP78, CHOP, and caspase-12.
2
bFGF treatment improves locomotor recovery in SCI rats and increases the survival of neurons in the spinal cord lesions.
3
bFGF inhibits ER stress-induced apoptosis by downregulating CHOP, GRP78, and caspase-12, and upregulates the neuroprotective factor GAP43.

Research Summary

This study investigates the mechanism of endoplasmic reticulum (ER) stress–induced apoptosis and the protective action of basic fibroblast growth factor (bFGF) in spinal cord injury (SCI). bFGF administration improved the recovery and increased the survival of neurons in spinal cord lesions in model rat. The protective effect of bFGF is related to the inhibition of CHOP, GRP78 and caspase-12, which are ER stress–induced apoptosis response proteins. The study concludes that bFGF's role in SCI recovery is related to the inhibition of ER stress–induced cell death via the activation of downstream signals, suggesting a new avenue for bFGF drug development in central neural system injuries.

Practical Implications

Therapeutic Potential

bFGF may be a suitable therapy for recovery from central nervous system injury diseases.

Drug Development

The work suggests a new trend for bFGF drug development in central neural system injuries, which are involved in chronic ER stress–induced apoptosis.

Underlying Mechanisms

Further studies are necessary to improve the pharmacodynamic actions and demonstrate the underlying mechanisms of bFGF.

Study Limitations

1
A single dose of bFGF was treated right after injury, postinjury treatment of optimal dose and extended time would better evaluate the therapeutic value in the future.
2
The 7-day outcome may not be long enough, which needs to be further investigated on the long-term neurological outcome, such as 2–3 weeks or longer period.
3
PC12 cell used in vitro is informative, future tests in spinal cord neuron cultures would be more persuasive.

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