Control study between behavioral and pathological findings of the transected spinal cord model in rats

doi:10.3969/j.issn.2095-4344.2014.36.019

Abstract

Abstract:

BACKGROUND: Ideal models of spinal cord injury should simulate human spinal cord injury, exclude confounding factors affecting effects, and have extensive repeatability. Spinal cord transection model is an ideal choice at present. Nevertheless, the operation is diverse, so therapeutic effects have great differences, and the research results lack of comparability.
OBJECTIVE: To compare and analyze behavioral changes and pathological features of rat hindlimb after spinal cord transection by establishing standardized model of transected spinal cord in rats.
METHODS: A total of 60 adult female Sprague-Dawley rats were randomly divided into sham surgery group (n=12), conventional spinal cord transection group (n=24) and microscopic spinal cord transection group (n=24). Each group was randomly assigned to 7-day, 14-day and 28-day groups according to time points after model establishment. T₉ vertebrae were considered as a center. Sham surgery group underwent laminectomy. Other groups underwent spinal cord transection. Thus, models of acute spinal cord injury were induced. Models in the conventional spinal cord transection group were established by conventional surgical methods. Models in the microscopic spinal cord transection group were established by standardization micromanipulation technique. At 7, 14 and 28 days after model establishment, motor function of hindlimb was evaluated using Basso, Beattie and Bresnahan (BBB) scoring system. Histopathology of transected spinal cord was observed. The thickness of the glial scar, the longitudinal distance between the two stumps, the transverse diameter of the spinal cord cavity and cerebrospinal fluid cyst formation were measured at the transected site of the spinal cord.
RESULTS AND CONCLUSION: In the sham surgery group, preoperative and postoperative BBB scores and pathology of the spinal cord did not clearly change. In the conventional spinal cord transection group and microscopic spinal cord transection group, complete paralysis of hindlimb was detected after model establishment. Hindlimb function did not recover in the conventional spinal cord transection group. At 1 to 2 weeks after model induction, spontaneous recovery of hindlimb function was visible in rats of the microscopic spinal cord transection group. Spinal pathology index value was significantly lower in the microscopic spinal cord transection group than in the conventional spinal cord transection group (P < 0.01). Pathological observations were not correlated with BBB scores in each group. These data indicated that standardized spinal cord transection method helps to eliminate individual differences and to quantitatively analyze and to compare studies addressing therapeutic effects.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: spinal cord injuries, microsurgery, pathology, models, animal

CLC Number:

R318

Yin Wen-hua, Lei Ying, Ma Guo-dong, Liu Guo-qiang, Chen Mu-ji, Hua Jin-chang. Control study between behavioral and pathological findings of the transected spinal cord model in rats[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(36): 5847-5854.

Figures/Tables 2

Quantitative analysis of experimental animals A total of 60 rats were divided into three groups. Three rats died in the conventional spinal cord transection group. Two rats died in the microscopic spinal cord transection group. Besides analyzing the reasons for death, dead rats were supplemented with new. Conditions and hindlimb behaviors after model induction Rats in the sham surgery group completely survived. BBB scores did not apparently alter before and after surgery. Complete hind limb paralysis was detected in the rats of conventional spinal cord transection and microscopic spinal cord transection groups. Three rats in the conventional spinal cord transaction group (12%) and two rats in the microscopic spinal cord transection group (8%) died of bladder rupture. Within 1 week after model establishment, the first section of hematuria was observed in 41 cases, including 17 cases (71%) in the conventional spinal cord transection group and 14 cases (58%) in the microscopic spinal cord transection group. Secondary urinary tract infection was detected in 15 cases, including 9 cases (38%) in the conventional spinal cord transection group and 6 cases (25%) in the microscopic spinal cord transection group. Rats in the microscopic spinal cord transection group affected unilateral hindlimb pressure sores (6 cases, 25%) and unilateral lower abdominal pressure sores (2 cases, 8%), which healed after active wound care. After model induction, hindlimb motor function did not recover in the rats of conventional spinal cord transection group. From 7 to 14 days after model induction, hindlimb motor function was gradually spontaneously recovered to some degrees in the microscopic spinal cord transection group. Joint motion and non-load-bearing lower limb paddling were detectable, showing significant differences between the microscopic spinal cord transection group and conventional spinal cord transection group (P < 0.01; Table 1). Histopathological observation and its relationship with BBB score No significant alterations in histology were detected before and after surgery in the sham surgery group. At 7 days after model induction, continuity in the spinal cord was completely interrupted in the conventional spinal cord transection group and microscopic spinal cord transection group. The bilateral stumps of the spinal cord were destroyed, forming liquefaction necrosis. Obvious dural hypertrophy was observed. At 14 days, scar in the transected area was healed, and cavity formed in the bilateral stumps of the spinal cord. Compared with the conventional spinal cord transection group, transected area was narrow, and bilateral stumps were relatively regular. Dura and scar hyperblastosis was visible surrounding the transected region. Moreover, from 7 days, central canal occlusion and local cerebrospinal fluid sac were detected in the stump at the side of head. With prolonged time, cysts volume increased. In the conventional spinal cord transection group, spinal cord tissue was clubbed in the stump of the spinal cord, and no cerebrospinal fluid sac appeared. No significant difference in spinal cord diameter was detectable between conventional spinal cord transection group and microscopic spinal cord transection group. All pathological measures and calculated indicators were significantly higher in the conventional spinal cord transection group than in the microscopic spinal cord transection group (P < 0.01; Table 2, Figures 1-3). Statistical analysis suggested that spinal pathology observations were not correlated with BBB score in rats (P > 0.05)."

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