E-ISSN: 1019-5157
ISSN: 2651-5024
Research
Dose-Dependent Neuroprotection by Bevacizumab in a Hyperglycemic Trigeminal Injury Model: A Novel In Vitro Platform for Metabolic Neuropathy Research
Kaan Kirimli✉ ,
Ali Riza Guvercin ,
Ugur Yazar ,
Ahmet Ayar ,
Demet Evleksiz ,
Adem Dogan
DOI: 10.5137/1019-5149.JTN.49936-25.3
Article in Press
Corresponding Author:
Kaan Kirimli (md.kaan61@gmail.com)
Abstract
Aim
Trigeminal neuralgia (TGN) is a disease characterized by recurrent episodes of severe pain in one or more branches of the trigeminal nerve, and the effectiveness of current treatments is limited, especially in patients with metabolic disorders. This study provides preclinical data by presenting the first comprehensive in vitro model examining the dose-dependent neuroprotective effects of the anti-VEGF (Vascular Endothelial Growth Factor) agent Bevacizumab in a hyperglycemia-induced TGN model.
Material and Methods
Trigeminal ganglion neurons were isolated from Sprague-Dawley rats (n = 10) and cultured under normoglycemic (5.5 mM), hyperglycemic (50 mM glucose), and hyperosmolar (50 mM mannitol) conditions. Bevacizumab was administered at four doses (0.0252.5 mg/ml). Cell viability and proliferation were monitored in real time for 160 hours with the xCELLigence RTCA system.
Results
Hyperglycemia reduced cell index by 52% compared to normoglycemia (p < 0.0001). Bevacizumab restored viability in a dose-dependent manner, with maximal efficacy observed at 1 mg/ml (68.9%, p < 0.0001). The high dose (2.5 mg/ml) was limited to 58% recovery (p=0.01182), indicating excessive inhibition of the neurotrophic role of VEGF.
Conclusion
Bevacizumab showed a neuroprotective effect through VEGF inhibition in the hyperglycemic TGN model and protected trigeminal neurons against hyperglycemic damage. Dose optimization is important for therapeutic efficacy, and phase I studies are required to proceed to clinical application.
Trigeminal neuralgia (TGN) is a disease characterized by recurrent episodes of severe pain in one or more branches of the trigeminal nerve, and the effectiveness of current treatments is limited, especially in patients with metabolic disorders. This study provides preclinical data by presenting the first comprehensive in vitro model examining the dose-dependent neuroprotective effects of the anti-VEGF (Vascular Endothelial Growth Factor) agent Bevacizumab in a hyperglycemia-induced TGN model.
Material and Methods
Trigeminal ganglion neurons were isolated from Sprague-Dawley rats (n = 10) and cultured under normoglycemic (5.5 mM), hyperglycemic (50 mM glucose), and hyperosmolar (50 mM mannitol) conditions. Bevacizumab was administered at four doses (0.0252.5 mg/ml). Cell viability and proliferation were monitored in real time for 160 hours with the xCELLigence RTCA system.
Results
Hyperglycemia reduced cell index by 52% compared to normoglycemia (p < 0.0001). Bevacizumab restored viability in a dose-dependent manner, with maximal efficacy observed at 1 mg/ml (68.9%, p < 0.0001). The high dose (2.5 mg/ml) was limited to 58% recovery (p=0.01182), indicating excessive inhibition of the neurotrophic role of VEGF.
Conclusion
Bevacizumab showed a neuroprotective effect through VEGF inhibition in the hyperglycemic TGN model and protected trigeminal neurons against hyperglycemic damage. Dose optimization is important for therapeutic efficacy, and phase I studies are required to proceed to clinical application.
Keywords
Trigeminal neuralgia
Bevacizumab
Hyperglycemia
Neuroprotection
xCELLigence