Investigation of the therapeutic effect of bevacizumab in an experimental model of sciatic nerve traumatic injury in rats

Introduction-Goal: Peripheral nerve damage is a condition that may cause motor and sensory dysfunction and is still an important issue due to the difficulty of treating nerve damage. With increasing industrialization, peripheral nerve injuries have become one of the important and frequently encountered injuries in our society. These injuries, which can cause psychological, material and functional losses, are a challenging process for patients. As it may cause functional incapacity and losing work force of the person, it may affect the society financially. Therefore, newly released molecules for the treatment of peripheral nerve damage have been studying and this may be a hope for patients. Depending on the level of peripheral nerve damage, sensory and motor dysfunctions may develop in patients. The underlying causes are related to nerve damage and the level of damage. Acute and chronic symptoms occur over time after the damage. Although rare, spontaneous recovery may occur (depending on the level of damage and the regenerative capacity of the person). Histological examination and electrophysiological tests (and in some cases imaging methods such as magnetic resonance imaging to detect the integrity of the nerve) are performed. After the damage, histopathological changes occur in the distal and proximal parts of the nerve. Functional recovery after peripheral nerve injury is usually not good; but regeneration is possible in the peripheral nervous system compared to the central nervous system. However, this does not happen spontaneously or the spontaneous process is limited and slow. Therefore, studies to reveal pharmacological treatment applications that can contribute to this regeneration are extremely important. In order for a peripheral nerve to continue its function, the peripheral nerve must have a connection with the cell body in the central nervous system and adequate oxygen support must be provided. In the case of ischemia, many biochemical and pathological changes occur as a result of oxidative stress and lipid peroxidation resulting from the disruption of the blood nerve barrier. Although many drug trials related to this situation have been made, no results have been obtained completely. Studies have shown that vascular endothelial growth factor (VEGF) has a neuroprotective effect on the nervous system through angiopoietins, and it has been proven to have an effect on the oxygenation and regeneration of nerve tissues by increasing vascular permeability. In many studies, VEGF antagonists have been shown to be effective in healing tissues by reducing edema, preventing free radical and scar tissue formation or degeneration. Although it is known that angiogenesis has a beneficial effect in an injured nervous system region, it has been shown that excessive angiogenesis can be harmful and limited angiogenesis is required for optimal recovery. Thereby it is thought that anti-VEGF therapy may have a neuroprotective effect on nervous system pathologies by providing limited angiogenesis. Materials and Methods: In the study, a total of 40 Wistar Albino rats (20 males and 20 females) were used in 4 groups, with 10 (n=10) in each group. The groups were divided into 4 groups: the control group, the trauma group, the medium-dose bevacizumab administered group, and the high-dose bevacizumab administered group. Motor coordination tests (Rotarod), thermal plantar tests and right lower extremity EMG tests were performed on all subjects. Afterwards, a nerve injury model was created by clipping the right sciatic nerve to rats. In the control group, no damage was applied after the sciatic nerve dissection and the layers were closed. Bevacizumab (Anti VEGF) treatment was given to the treatment groups on immediate, the seventh and fourteenth days of the trauma. The doses of these treatments were 5mg per kilogram in the medium dose treatment group and 10 mg per kilogram in the high dose treatment group. Bevacizumab (Anti VEGF) was calculated and administered intraperitoneally. All groups were taken into care for 21 days after the procedures. The rats were subjected to motor coordination tests, thermal plantar test and EMG measurements again on the 21st day, then sacrification was performed by decapitation method. Afterwards, the right sciatic nerves were removed 1 cm proximal and 1 cm distal to the traumatized area and examined histopathologically. Results: Bevacizumab (Anti VEGF), when used in appropriate doses in the sciatic nerve trauma injury model, reduces the development of scar tissue, edema and degeneration, limits angiogenesis. From this aspect, it has a neuroprotective effect on nerve damage, positively affecting nerve recovery. In the statistical analyzes, significant differences were found between the trauma group and the groups that received high-dose and medium-dose treatment. Similarities were found between the treatment groups (medium- and high-dose) and the control group. Histopathologically, it was proved that bevacizumab reduced edema, inflammation and degeneration. Conclusion: As a result, in the peripheral nerve trauma injury model, Bevacizumab (Anti VEGF) treatment helped to heal nerve damage by providing controlled angiogenesis, reducing degeneration and edema. Key Words: Sciatic nerve, Peripheral nerve, Bevacizumab, Anti VEGF, Degeneration, Edema, Angiogenesis.