Caspian Journal of Veterinary Sciences

Caspian Journal of Veterinary Sciences

Betaine improves histopathologic recovery after sciatic nerve crush injury in rats: a dose–response experimental study

Articles in Press

Document Type : Original Article

Authors
Kosar Javareshkian 1
Ahmad Asghari 1
Pejman Mortazavi 2
1 Department of Veterinary Clinical Sciences, SR.C., Islamic Azad University, Tehran, Iran.
2 Department of Pathobiology, SR.C., Islamic Azad University, Tehran, Iran.
10.22034/cjvs.2026.582570.1069
Abstract
Peripheral nerve crush injuries can lead to incomplete structural recovery due to inflammation, edema, and cellular stress. Betaine, a natural osmolyte and methyl donor, has been investigated for potential cytoprotective and immunometabolic effects relevant to neural injury models. To evaluate the dose-range effects of betaine on histopathologic indices of sciatic nerve regeneration in a rat crush injury model. Forty male rats were allocated to five groups (n=8 each): non-injured control, untreated crush injury, and three crush-injury groups treated with betaine (100, 200, or 400 mg/kg/day). At postoperative day 21, harvested sciatic nerves underwent standardized histopathologic assessment using a semi-quantitative composite regeneration score (0–16) derived from perineurium/epineurium formation, inflammatory cell presence, axonal swelling, and density of healthy axons. Composite regeneration scores differed significantly among groups (one-way ANOVA, p < 0.001). The injury-only group demonstrated markedly lower scores than controls. Higher composite scores were observed in the 200 and 400 mg/kg/day groups compared to untreated injury, whereas the 100 mg/kg/day group did not differ significantly from injury-only animals. Healthy axon density showed significant overall group differences (p < 0.05), with descriptive trends toward higher mean values in betaine-treated groups; however, post-hoc comparisons did not demonstrate statistically significant differences between treated and untreated injured groups. In this rat sciatic nerve crush model, betaine administration was associated with higher composite histopathologic regeneration scores at higher tested doses (200–400 mg/kg/day). These findings support further experimental investigation incorporating functional and mechanistic outcomes to clarify the potential role of betaine in peripheral nerve recovery.



Keywords
Betaine
Histopathology
Rat
Peripheral nerve regeneration
Sciatic nerve
Subjects
Alipourfard, F; Alirezaei, M; Shajiee, H and Hojati, V (2023). Betaine attenuates oxidative stress and cognitive dysfunction in an amyloid beta-induced rat model of Alzheimer’s disease. Res. Pharm. Sci., 18: 372–382.
Arumugam, MK; Paal, MC; Donohue, TM; Ganesan, M; Osna, NA and Kharbanda, KK (2021). Beneficial effects of betaine: A comprehensive review. Biol., 10: 456.
Bridge, PM; Bal,l DJ; Mackinnon, SE and Dellon, AL (1994), Nerve crush injuries--a model for axonotmesis. Exp. Neurol., 127: 284–290.
Caner, B; Kafa, MI; Bekar, A; Kurt, MA; Karli, N and Cansev, M (2012) Intraperitoneal administration of CDP-choline or a combination of cytidine plus choline improves nerve regeneration and functional recovery in a rat model of sciatic nerve injury. Neurol Res., 34: 238–245.
Chen, ZL; Yu, WM and Strickland, S (2007), Peripheral regeneration. Ann. Rev. Neurosci., 30: 209–233.
de Medinaceli, L; Freed, WJ and Wyatt, RJ (1982), An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp. Neurol., 77: 634–643.
Gordon, T (2020), Peripheral nerve regeneration and muscle reinnervation. Int. J. Mol. Sci., 21: 8652.
Hare, GMT; Evans, PJ and Mackinnon, SE (1993), Walking track analysis: utilization of individual footprint parameters. Ann. Plastic Surgery, 30: 147–153.
Hassanpour, S; Rezaei, H and Razavi, SM (2020), Anti-nociceptive and antioxidant activity of betaine on formalin- and writhing tests induced pain in mice. Behavioural Brain Res., 390: 112699.
Im, AR; Kim, YH; Uddin, MR; Kim, YS and Chae, S (2013), Neuroprotective effects of betaine on rotenone-induced cytotoxicity via the inhibition of reactive oxygen species generation in SH-SY5Y cells. Cell. Mol. Neurobiol., 33: 977–986.
Jessen, KR and Mirsky, R (2016). The repair Schwann cell and its function in regenerating nerves. J. Physiol., 594: 3521–3531.
Kanbak, G; Arslan, OC; Dokumacioglu, A; Kartkaya, K and Inal, ME (2008), Effects of chronic ethanol consumption on brain synaptosomes: Protective role of betaine. Neurochem. Res., 33: 539–544.
Knight, LS and Baskin, DS (2023). Betaine and its role in neuroprotection and peripheral nerve recovery: a review of current evidence. Front. Neurosci., 17: 1214976.
Li, Q; Li, X; Wang, L; Zhang, Y and Chen, L (2022). Betaine protects rats against ischemia/reperfusion injury-induced brain damage. J. Neurophysiol., 127: 252–261.
O'Brien, EJ (2022), Promoting nerve regeneration: Electrical stimulation, extracellular matrix molecules, and the promise of CRISPR technology. Physiol., 37: 223–235.
Park, MJ; Kim, SR; Huh, H; Jung, JH and Kim, YC (1994). Betaine attenuates glutamate-induced neurotoxicity in primary cultured brain cells. Arch. Pharm. Res., 17: 343–347.
Scheib, JL and Hoke, A (2013), Advances in peripheral nerve regeneration. Nature Rev. Neurol., 9: 668–676.
Zhang, M (2022). Betaine inhibits NLRP3 inflammasome activation and induces autophagy via the AMPK/SIRT1 pathway. Oxidative Med. Cell. Longevity, 2022: 9313436.
Zhao, G; He, F and Wu, C (2018), Betaine in inflammation: mechanistic aspects and applications. Front. Immunol., 9: 1070.
Caspian Journal of Veterinary Sciences

Articles in Press, Accepted Manuscript
Available Online from 08 November 2026

  • Receive Date 20 May 2026
  • Accept Date 30 May 2026