The evaluation of repeated epidural dexmedetomidine injections on neurotoxicity in rabbits

In this study, we evaluated the effects of dexmedetomidine, an alpha-2 agonist, upon the neurons by repeated epidural administrations in therabbits via light microscope for neurotoxicity.Our study was performed in 2 groups with 20 male, albino NewZealand rabbits, weighing 1.5-2 kg. In the first day of the study, epiduralcatheter was placed into the all rabbits under general anesthesia. 0.5 ml 1%dexmedetomidine (diluted with 0.9% saline) to dexmedetomidine group and0.5 ml isotonic saline to control group were administered through epiduralcatheter during 14 days and the rabbits were observed for motor alterations.One day after the last injection, the rabbits were anesthetized with the samedrugs and then laminectomy was performed in 30 minutes. The section of 5cm of spinal cord was dissected fastidiously from 1 cm of the rostral of thecatheter tip and immediately protected in the same fixative. Tissue blockswere embedded in paraffin after fixation and spinal cord sections weredivided transversely into 5 slices. These samples were stained for theevaluation by light microscope. Microscope studies were performed by ablind histolog. Medulla spinalis and dorsal root ganglions were evaluated foredema, myelin injury and choriolysis.No motor, sensory and behavioural differences were obtained during14 days of study in the rabbits. There was no bacterial or fungalinflammation according to the histopathological examination. Pathologicalfindings like degeneration, inflammation or bleeding in medulla spinalis anddorsal root ganglions were not observed by light microscope in the controlgroup. No pathological finding leading to toxic effect was seen and anterior,posterior, lateral horn of medulla spinalis, central channel, white matter anddorsal root ganglions were obtained as normal due to HE (hematoxylin-eosin) staining. No difference was seen by dexmedetomidineadministration. There was no positive stained cell in anterior, posterior,lateral horn of medulla spinalis, central channel, white matter and dorsalroot ganglions according to TUNEL immunostaining for apoptotic celldetection. This situation was obtained the same in both control anddexmedetomidine group. No difference was found between the groups foriNOS and eNOS due to NOS staining. In morphometric examination therewas no histopathological disorder, gliosis related to toxic effect as seen nodifference in total cell count or neurotoxic effect because of unchangedneuron number according to the HE and NOS staining related todexmedetomidine administration.Consequently; as there is no finding supporting neurotoxicity due tolight microscope evaluations, we consider that repeated epiduraladministration of dexmedetomidine has no neurotoxic effect.