Effect of citicoline on nerve healing in sciatic nerve crush injury in rats with circadian rhythm disorder

Peripheral nerve injuries are a common occurrence in plastic surgery emergency cases. Failure to achieve full recovery is a problem that needs to be addressed. Many factors affecting healing have been studied extensively, and various agents have been tried in addition to surgical treatment. Citicoline, a phospholipid molecule, has been shown to have positive effects on central nervous system traumas. However, there are limited studies demonstrating its effectiveness on peripheral nerve healing. Trauma patients with peripheral nerve injuries have been observed to have stress disorders and accompanying sleep-wake problems. Circadian rhythm disruption affects many systems and is known to adversely affect wound healing. However, there is no study demonstrating its effect on peripheral nerve healing. This study aimed to investigate the effects of citicoline and circadian rhythm disruption on nerve healing by creating a crush-type injury in the sciatic nerve. Forty-one female Sprague Dawley rats weighing between 250-270 grams were used. Rats were randomly divided into 6 groups. Crush-type injuries were created in the left sciatic nerve of rats in four groups. Citicoline was administered at a dose of 600 mg/kg/day for 7 days via gavage. The groups were defined as follows: control group, group with disrupted circadian rhythm, group with sciatic nerve injury, group with sciatic nerve injury and citicoline administration, group with sciatic nerve injury, citicoline administration, and disrupted circadian rhythm, and group with disrupted circadian rhythm and sciatic nerve injury. Video gait analysis was performed on all groups at the 4th, 8th, and 12th weeks. Electromyography was performed at the 4th and 12th weeks. Sacrifice was performed at the 12th week, and histomorphological appearance, axon count, and axon diameter were evaluated in the sciatic nerve tissues obtained. In our study, it was demonstrated functionally, electrophysiologically, and histopathologically that citicoline positively affected nerve healing in peripheral nerve injuries, while circadian rhythm disruption had a negative effect. It was shown that questioning the sleep cycle in patients followed up due to peripheral nerve injuries and planning supportive treatments when necessary is crucial for the healing process.