Acute theophylline exposure modulates breathing activity through a cervical contusion

Cervical spinal contusion injuries are the most common form of spinal cord injury (>50%) observed in humans. These injuries can result in the impaired ability to breathe. In this study we examine the role of theophylline in the rescue of breathing behavior after a cervical spinal contusion. Previous research in the C2 hemisection model has shown that acute administration of theophylline can rescue phrenic nerve activity and diaphragmatic EMG on the side ipsilateral to injury. However, this effect is dependent on intact and uninjured pathways. In this study we utilized a cervical contusion injury model that more closely mimics the human condition. This injury model can determine the effectiveness of therapeutic interventions, in this case theophylline, on the isolated contused pathways of the spinal cord. Three weeks after a 150 kD C3/4 unilateral contusion subjects received a 15 mg/kg dose of theophylline prior to a contralateral C2 hemisection. Subjects that received theophylline were able to effectively utilize damaged pathways to breathe for up to 2 min, while subjects treated with saline were unable to support ventilation. Through these experiments, we demonstrate that theophylline can make injured pathways that mediate breathing more effective and therefore, suggest a potential therapeutic role in the critical time points immediately after injury.