Turkish Neurosurgery 2024 , Vol 34 , Num 6
Mediation of Epigenetic Mechanisms in the Regenerative Effect of Uridine in a Rat Model of Sciatic Nerve Injury
Ali Imran OZMARASALI1,Cansu KOC2,Huseyin UZABACI3,Mehmet CANSEV2,Ilker Mustafa KAFA3,Ahmet BEKAR1
1Bursa Uludag University Faculty of Medicine, Department of Neurosurgery, Bursa, Türkiye
2Bursa Uludag University Faculty of Medicine, Department of Pharmacology, Bursa, Türkiye
3Bursa Uludag University Faculty of Medicine, Department of Anatomy, Bursa, Türkiye
DOI : 10.5137/1019-5149.JTN.45425-23.2 AIM: To investigate the possible mediation of epigenetic mechanisms underlying the regenerative effect of uridine in a sciatic nerve transection rat model.

MATERIAL and METHODS: Fifty adult male rats were randomized to sham, control, and uridine groups. After unilateral transection and primary anastomosis of the right sciatic nerve, a single daily dose of saline (1 ml/kg; sham and control groups) or uridine (500 mg/kg; uridine group) was injected intraperitoneally for a week. The sciatic nerves were removed en bloc on the eighth day and levels of histone deacetylase 1 (HDAC1), acetylated histone-H3, and acetylated histone-H4 were analyzed in nerve homogenates. The number of myelinated axons in the sciatic nerve specimens was analyzed histomorphologically.

RESULTS: The HDAC1 levels were significantly greater in the control group than in the sham (p<0.001) and uridine (p<0.01) groups. Compared to the sham group, the acetylated histone-H3 and histone-H4 levels decreased in the control group (by 81.49% and 79.98%, respectively for both; p<0.001) and increased significantly in the uridine group (by 62.54% and 51.68% respectively; p<0.01, p<0.05). The number of myelinated axons decreased significantly (p<0.001) in the control group, which was enhanced significantly by uridine administration.

CONCLUSION: Epigenetic mechanisms may partly mediate the regenerative effect of uridine treatment in a rat model of sciatic nerve injury. Our data provides novel insights in the management of peripheral nerve damage and suggests potential benefit of uridine for degenerative diseases in which epigenetic impairments are involved. Keywords : Uridine, Sciatic Nerve Injury, Peripheral Nerve Regeneration, Histone Deacetylase, Epigenetic

Corresponding author : Ahmet BEKAR, abekar@uludag.edu.tr