Intravenous taxol therapy promotes breathing after cervical spinal cord injury
Dr. Warren Alilain of MetroHealth
More than half of all spinal cord injuries (SCI) are at the cervical level. These injuries can result in the disruption of the respiratory motor pathways leading to the innervation of the diaphragm, resulting in the need for mechanical ventilation. To examine the neuronal circuitry involved in cervical SCI and potential interventions, our laboratory utilizes a C2 lateral hemisection. This model induces paralysis of the hemi-diaphragm ipsilateral to the hemisection. By leaving one side of the diaphragm still active, this model allows us to examine the breathing circuitry affected and spared by cervical SCI without the need for artificial ventilation of experimental subjects. A recent investigation has shown that the microtubule stabilizer paclitaxel (Taxol) can improve outcomes in thoracic injury. In the thoracic injury model, paclitaxel has been shown to reduce the perineuronal (PNN) net and increase serotonin (5-HT) after injury. However, its application in cervical injury is untested. Here we examined the therapeutic potential of paclitaxel on the recovery of breathing after a C2 spinal hemisection. Subjects received various (0.5mg, 0.25mg, & 0.125mg) doses of systemic i.v. paclitaxel at 48 hours postinjury. Preliminary data indicate that cervical SCI subjects that receive Taxol have improved respiratory motor function compared to vehicle treated animals in a dose dependent fashion. Based on these encouraging results investigating a combination treatment of paclitaxel and rehabilitative therapy is warranted. Future studies examining this multi-modality strategy are planned.
Society for Neuroscience Chicago Spinal Cord Injury I and Plasticity
Support: Neilsen Postdoctoral Fellowship Research Grant – 295998 (Kevin Hoy)
Neilsen Foundation- 221988 (Warren Alilain) The MetroHealth System (Warren Alilain)
Disclosures: K.C. Hoy: None. F.J. Jacono: None. F. Bradke: None. W.J. Alilain: None.
Authors: *K. C. HOY1, F. J. JACONO2,3, F. BRADKE4, W. J. ALILAIN5,6; 1Neurol., Metrohealth Med. Ctr., Cleveland, OH; 2Louis Stokes Cleveland VA Med. Ctr., Cleveland, OH; 3Univ. Hosp. Case Med. Ctr., Cleveland, OH; 4German Ctr. for Neurodegenterative Dis., Bonn, Germany; 5MetroHealth Med. Ctr., Cleveland, OH; 6Case Western Reserve Med. Sch., Cleveland, OH