In vivo Neurotoxicity Study of Restorative Solution in Rats
- 발행기관 고려대학교
- 발행년도 2008
- 학위수여년월 2008. 2
- 학위명 박사
- 학과 대학원 의학과 재활의학전공
- 식별자(기타) DL:000018612605
- 서지제어번호 000045444482
초록/요약
Background and purpose: There is a growing interest in the development of treatment option in disc disruption of patients with low back and neck pain, which promotes tissue repair rather than tissue removal or destruction. Injection of restorative solution into intervertebral discs has shown to be effective with the stimulation of connective tissue healing. However, the safety of this solution for the surrounding nerve tissues not for the discs has not been evaluated. This study was designed to assess neurotoxicity of restorative solution being injected into the subarachnoid space and to determine the safety range of dosage. Materials and Methods: This was prospective controlled animal study. Forty 300-500gm Sprague-Dawley male rats were divided randomly into four experimental groups. Control, Group A (normal saline injection), Group B (conventional restorative solution; one-fold concentrated-solution injection; 5% glucosamine hydrochloride (HCl), 2% chondroitin sulfate and 2% bupivacaine HCl), Group C (two-fold concentrated solution; 10% glucosamine HCl, 2% chondroitin sulfate and 2% bupivacaine HCl) and Group D (four-fold concentrated solution; 20% glucosamine HCl, 2% chondroitin sulfate and 2% bupivacaine HCl). The solution was injected directly into the subarachnoid space using microscope. For the sensory test, behavioral change with cold (tail flick) or mechanical (von Frey) allodynia was conducted 1 day prior to the injection and day 3 and day 7 after injection. The rats were sacrificed 7 days after injection. The spinal cord and nerve roots in all groups were dissected out and stained with hematoxyline-eosin. Histopathologic evaluation was performed using light microscope by a neuropathologist blinded to the intrathecal injection received. Nerve injuries were graded according to a scoring system by Okazaki et al. Results: There was no significant difference in sensory function using allodynia test before and after injection of 4 different solutions in all rats. In control, group A, and group B with conventional restorative solution, there was no definite neurotoxicity in spinal cord or nerve roots on histopathologic examination. Neurotoxicities with edema or demyelination in spinal cord were noted 40 % and 50 % for mild category and 20 % and 10 % for moderate category in group C and D, respectively. In nerve roots, mild neurotoxicities were observed in 30 % and 50 % for mild category and 30 % and 20 % for moderate category in group C and D, respectively. There was no severe category of neurotoxicity in all groups. Conclusion: Conventional restorative solution is safe for the surrounding nerve tissues even when there is leakage into the subarachnoid space. However, over 10 % of glucosamine HCl in restorative solution could evoke mild edema or demyelination in spinal cord or nerve roots even if there was no sensory change clinically.
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