E-ISSN: 1019-5157
ISSN: 2651-5024
Research
Vigabatrin Mitigates Secondary Injury in Traumatic Spinal Cord Injury via Potent Inhibition of Ferroptosis: A Novel Neuroprotective Mechanism
İLÇİM ERMUTLU✉ ,
ŞERİFE EFSUN ANTMEN ,
TOLGA AKBIYIK ,
HAMİDE SAYAR
DOI: 10.5137/1019-5149.JTN.50046-25.7
Article in Press
Corresponding Author:
İLÇİM ERMUTLU (drilcimermutlu@gmail.com)
Abstract
Aim
Traumatic spinal cord injury (TSCI) involves secondary injury via apoptosis, inflammation, oxidative stress, and ferroptosis. This study investigated the neuroprotective effects of Vigabatrin, a GABA-transaminase inhibitor, in a rat TSCI model, focusing on its potential to modulate the ferroptosis pathway.
Material and Methods
Wistar rats were randomly assigned to Control, Sham, TSCI, and TSCI+Vigabatrin groups (n=8/group). TSCI was induced via a weight-drop model. Locomotor function was assessed using the Basso, Beattie, Bresnahan (BBB) scale. At 24 hours post-injuryan acute phase critical for secondary injury mechanismsspinal cord tissues were analyzed for histopathology and biochemical markers of apoptosis (Caspase-3), inflammation (MPO), oxidative stress (MDA), and ferroptosis (GSH, GPX4, ACSL4, SLC7A11).
Results
The TSCI group showed severe locomotor deficits, histopathological damage, and increased Caspase-3, MPO, and MDA levels (p < 0.0001). Vigabatrin treatment significantly improved BBB scores and tissue architecture while reducing these markers (p < 0.0001). TSCI also induced ferroptosis, evidenced by decreased GSH, GPX4, and SLC7A11 and increased ACSL4 (p < 0.0001). Vigabatrin administration effectively reversed these ferroptotic changes, restoring the antioxidant system and suppressing pro-ferroptotic ACSL4 (p < 0.0001).
Conclusion
Vigabatrin demonstrates significant neuroprotection in the acute phase of a rat TSCI model. Its therapeutic effect is mediated by attenuating apoptosis, inflammation, and oxidative stress, and appears to involve the modulation of the ferroptosis pathway. These findings suggest Vigabatrin is a promising agent for acute TSCI treatment, though further long-term studies are warranted.
Traumatic spinal cord injury (TSCI) involves secondary injury via apoptosis, inflammation, oxidative stress, and ferroptosis. This study investigated the neuroprotective effects of Vigabatrin, a GABA-transaminase inhibitor, in a rat TSCI model, focusing on its potential to modulate the ferroptosis pathway.
Material and Methods
Wistar rats were randomly assigned to Control, Sham, TSCI, and TSCI+Vigabatrin groups (n=8/group). TSCI was induced via a weight-drop model. Locomotor function was assessed using the Basso, Beattie, Bresnahan (BBB) scale. At 24 hours post-injuryan acute phase critical for secondary injury mechanismsspinal cord tissues were analyzed for histopathology and biochemical markers of apoptosis (Caspase-3), inflammation (MPO), oxidative stress (MDA), and ferroptosis (GSH, GPX4, ACSL4, SLC7A11).
Results
The TSCI group showed severe locomotor deficits, histopathological damage, and increased Caspase-3, MPO, and MDA levels (p < 0.0001). Vigabatrin treatment significantly improved BBB scores and tissue architecture while reducing these markers (p < 0.0001). TSCI also induced ferroptosis, evidenced by decreased GSH, GPX4, and SLC7A11 and increased ACSL4 (p < 0.0001). Vigabatrin administration effectively reversed these ferroptotic changes, restoring the antioxidant system and suppressing pro-ferroptotic ACSL4 (p < 0.0001).
Conclusion
Vigabatrin demonstrates significant neuroprotection in the acute phase of a rat TSCI model. Its therapeutic effect is mediated by attenuating apoptosis, inflammation, and oxidative stress, and appears to involve the modulation of the ferroptosis pathway. These findings suggest Vigabatrin is a promising agent for acute TSCI treatment, though further long-term studies are warranted.
Keywords
Ferroptosis
Neuroprotection
Oxidative Stress
Spinal Cord Injuries
Vigabatrin