Preventing Venous Thromboembolism After Thoracic or Thoracolumbar Spinal Fusion

Abstract

The spinal cord is vulnerable to ischemic injury due to trauma, vascular malformations and correction of thoracic aortic lesions. Riluzole, a sodium channel blocker and anti-glutamate drug has been shown to be neuroprotective in a model of ischemic spinal cord injury, although the effects in clinically relevant ischemia/reperfusion models are unknown. Here, we examine the effect of riluzole following ischemia–reperfusion injury to the spinal cord.Female rats underwent high thoracic aortic balloon occlusion to produce an ischemia/reperfusion injury. Tolerance to ischemia was evaluated by varying the duration of occlusion. Riluzole (8 mg/kg) was injected intraperitoneally 4 h after injury. Locomotor function (Basso, Beattie and Bresnahan (BBB) scale) was assessed at 4 h, 1 day, and 5 days post-ischemia. Spinal cords were extracted and evaluated for neuronal loss using immunohistology (choline acetyltransferase (ChAT) and neuronal nuclei (NeuN)), inflammation (CD11b), astrogliosis (glial fibrillary acidic protein – GFAP) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).Ischemic injury lasting between 5.5 and 6.75 min resulted in delayed paraplegia, whereas longer ischemia induced immediate paraplegia. When riluzole was administered to rats that underwent 6 min of occlusion, delayed paraplegia was prevented. The BBB score of riluzole-treated rats was 11.14 ± 4.85 compared with 1.86 ± 1.07 in control animals. Riluzole also reduced neuronal loss, infiltration of microglia/macrophages and astrogliosis in the ventral horn and intermediate zone of the gray matter. In addition, riluzole reduced apoptosis of neurons in the dorsal horn of the gray matter.Riluzole has a neuroprotective effect in a rat model of spinal cord injury/reperfusion when administered up to 4 h post-injury, a clinically relevant therapeutic time window.