Ratlarda spinal kord yaralanmasında bevacizumabın etkilerinin araştırılması

Spinal cord injury, which is still a major problem today, continues to be one of the most difficult diseases to treat. It can be an important issue for the patient and society, both psychologically and financially. Therefore, promising results can be obtained by studying newly released molecules for the treatment of spinal cord injuries. Spinal cord trauma has basically two stages as primary and secondary injury. Primary injury is structural damage to the spine and spinal cord caused by the first traumatic event as a result of mechanical compression on the spinal cord segment. In besides to primary structural injuries, glial cells and nerve cells in the spinal cord are also injured. By initiation of cellular inflammatory cascades; perfusion of the spinal cord is impaired, and thereby hypoxic state causes structural damage to glial and nerve cells. The resulting structural and cellular damage triggers secondary injury. As the name suggests, the second injury cascade that develops after the primary injury encompasses a series of changes that begin a few hours later and last up to 6 months. As a result of these processes, spinal cord nutrition deteriorates and edema increases, and efforts for regeneration in nerve cells begin, but are mostly insufficient. In general, experimental treatments are aimed at preventing secondary damage and contributing to neuroregeneration. According to the studies, it is possible to provide neuroregeneration by both providing revascularization and reducing the edema occurring in the secondary damage and recovery period; by increasing blood supply and removing harmful substances such as free radicals in the trauma area. However, the revascularization must be in a certain balance. In addition to the lack of sufficient vascularization in the damaged spinal cord area, it can also be a problem if it is more than necessary. VEGF-type drugs have been used experimentally in these damage models before, and besides their effects on reducing secondary damage by increasing vascularization, neuroprotective effects on neural tissues damaged after trauma have been shown. However, it has recently been thought that anti-VEGF drugs may have a positive effect on recovery after spinal cord injuries by preventing excessive vascularization. It is thought that these effects are achieved basically by reducing edema after spinal cord injury, facilitating the delivery of oxygen and energy resources to the cells, providing a limited angiogenesis, preventing excessive glial scar tissue formation, and thus increasing the efficiency in the nutrition of nerve cells. Due to these properties, it is estimated that they may have neuroprotective effects. Material&Methods: In the study, a total of 60 (30 male and 30 female) rats were used in 6 groups, with 10 rats (n=10) in each group. The groups were divided into 6 groups as control group, trauma group, prophylaxis group, trauma and low dose bevacizumab administered group, trauma and medium dose bevacizumab administered group, trauma and high dose bevacizumab administered group. Motor coordination tests (Rotarod), thermal plantar tests and bilateral lower extremity EMG tests were performed on all subjects. Afterwards, thoracic laminectomy was performed on the rats and a spinal cord trauma model was created by clipping the spinal cord with a temporary aneurysm clip (Yasargil Aesculap FE 721K) Bevacizumab 2mg/kg was administered intrapertoneally to the prophylaxis group 1 hour before the trauma , to the treatment groups 2mg/kg to the low dose treatment group, 5mg/kg to the medium dose treatment group and 10mg/kg to the high dose treatment group immediately after the trauma. Bevacizumab was administered intraperitoneally. All groups were taken into care for one week after the procedures. At the end of one week, rats were subjected to motor coordination tests, thermal plantar test and EMG tests. Then sacrificed by decapitation, spinal cords were removed 2 cm cranial and 2 cm caudal to the injury site and examined histopathologically. Results: Bevacizumab (anti-VEGF), when used in appropriate doses in traumatic spinal cord injury, reduces edema by limiting angiogenesis and contributes positively to neuroregeneration in the healing of the traumatized area in spinal cord. In this way, a significant difference was found in the improvement of motor functions between the trauma group and the groups receiving high-dose treatment in motor and sensory neurologic functions (p=0.031). Neurologically significant improvement and improvement in sensory functions was found in spinal cord injury using bevacizumab. (p=0.036) These findings were supported by neurophysiological studies and a significant difference was found between the trauma group and the high-dose treatment group in electromyography (EMG) results (p=0.007). Bevacizumab (anti-VEGF) reduced post-traumatic edema histopathologically. In addition, the number of neurons with preserved function increased in those who received high-dose bevacizumab compared to those who did not. Conclusions: In conclusion, in the spinal cord trauma model in rats, Bevacizumab (anti-VEGF) treatment contributed to the improvement of motor and sensory neurological functions and partially EMG findings by suppressing edema and glial scar formation, by providing limited angiogenesis. Key Words: Spinal cord injury, Bevacizumab, anti VEGF, Neuroregeneration, Spinal cord trauma

Keyword: Bevacizumab = Bevacizumab ; Hayvan deneyleri = Animal experimentation ; Nörodejeneratif hastalıklar = Neurodegenerative diseases ; Spinal kord = Spinal cord ; Spinal kord yaralanmaları = Spinal cord injuries ; Sıçanlar = Rats ; Vasküler endotel büyüme faktörleri = Vascular endothelial growth factors