Guizar-Sahagun Gabriel, Martinez-Cruz Angelina, Franco-Bourland Rebecca E, Cruz-García Eduardo, Corona-Juarez Alvaro, Diaz-Ruiz Araceli, Grijalva Israel, Reyes-Alva Horacio J, Madrazo Ignacio
Research Unit for Neurological Diseases, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Department of Experimental Surgery, Proyecto Camina A.C., Mexico City, Mexico.
PLoS One. 2017 Apr 17;12(4):e0176105. doi: 10.1371/journal.pone.0176105. eCollection 2017.
Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the site of injury and adjacent segments. It is considered harmful because of its potential to aggravate secondary injury, and to interfere with axonal regeneration; it might also lead to an unfavorable environment for intralesional implants. Removal of hemorrhagic necrosis has been attempted before with variable results. The invasive nature of these procedures carries the risk of exacerbating damage to the injured cord. The overall objective for this study was to test several strategies for non-damaging removal of hemorrhagic necrosis and characterize the resulting cavity looking for a space for future intralesional therapeutic implants in rats with acute cord injury. Rats were subjected to graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three grades of myelotomy (extensive, medium sized, and small) were tested. Using the small surgical approach to debridement, early and late effects of the intervention were determined by histology and by analytical and behavioral analysis. Appearance and capacity of the resulting cavity were characterized. Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical approaches to debridement. However, bleeding in spared cord tissue was excessive after medium sized and extensive myelotomies but similar to control injured rats after small cord surgery. Small surgical approach to debridement produced no swelling nor acute inflammation changes, nor did it affect long-term spontaneous locomotor recovery, but resulted in modest improvement of myelination in rats subjected to both moderate and severe injuries. Cavity created after intervention was filled with 10 to 15 μL of hydrogel. In conclusion, by small surgical approach to debridement, removal of hemorrhagic necrosis was achieved after acute cord contusion thereby creating intramedullary spaces without further damaging the injured spinal cord. Resulting cavities appear suitable for future intralesional placement of pro-reparative cells or other regenerative biomaterials in a clinically relevant model of spinal cord injury.
脊髓损伤后早期,损伤部位及相邻节段会发生髓内出血性坏死。由于其可能加重继发性损伤、干扰轴突再生,还可能导致病灶内植入物的不良环境,因此被认为是有害的。此前曾尝试清除出血性坏死,结果不一。这些手术的侵入性有加剧损伤脊髓的风险。本研究的总体目标是测试几种无损清除出血性坏死的策略,并对形成的腔隙进行特征描述,以寻找在急性脊髓损伤大鼠中进行病灶内治疗性植入的空间。对大鼠进行分级脊髓挫伤,24小时后清除出血性坏死。测试了三种等级的脊髓切开术(广泛、中等大小和小)。采用小手术清创方法,通过组织学、分析和行为分析确定干预的早期和晚期效果。对形成的腔隙的外观和容量进行了特征描述。三种清创手术方法均实现了出血性坏死的满意清除。然而,中等大小和广泛脊髓切开术后,未损伤的脊髓组织出血过多,但小脊髓手术后与对照损伤大鼠相似。小手术清创方法未产生肿胀或急性炎症变化,也未影响长期自发运动恢复,但导致中度和重度损伤大鼠的髓鞘形成有适度改善。干预后形成的腔隙填充了10至15微升水凝胶。总之,通过小手术清创方法,在急性脊髓挫伤后实现了出血性坏死的清除,从而在不进一步损伤受损脊髓的情况下创建了髓内空间。在临床相关的脊髓损伤模型中,形成的腔隙似乎适合未来病灶内植入促修复细胞或其他再生生物材料。