Kuluz John, Samdani Amer, Benglis David, Gonzalez-Brito Manuel, Solano Juan P, Ramirez Miguel A, Luqman Ali, De los Santos Roosevelt, Hutchinson David, Nares Mike, Padgett Kyle, He Dansha, Huang Tingting, Levi Allan, Betz Randal, Dietrich Dalton
Pediatric Critical Care (R-131), University of Miami School of Medicine, 1611 NW 12th Avenue, Miami, FL 33136, USA.
J Spinal Cord Med. 2010;33(1):43-57. doi: 10.1080/10790268.2010.11689673.
To develop a new, clinically relevant large animal model of pediatric spinal cord injury (SCI) and compare the clinical and experimental features of pediatric SCI.
Infant piglets (3-5 weeks old) underwent contusive SCI by controlled cortical impactor at T7. Severe complete SCI was induced in 6 piglets, defined as SCI with no spontaneous return of sensorimotor function. Eight piglets received incomplete SCI, which was followed by partial recovery. Somatosensory evoked potentials, magnetic resonance imaging, neurobehavioral function, and histopathology were measured during a 28-day survival period.
Mean SCI volume (defined as volume of necrotic tissue) was larger after complete compared with incomplete SCI (387 +/- 29 vs 77 +/- 38 mm3, respectively, P < 0.001). No functional recovery occurred after complete SCI. After incomplete SCI, piglets initially had an absence of lower extremity sensorimotor function, urinary and stool retention, and little to no rectal tone. Sensory responses recovered first (1-2 days after injury), followed by spontaneous voiding, lower extremity motor responses, regular bowel movements, and repetitive flexion-extension of the lower extremities when crawling. No piglet recovered spontaneous walking, although 4 of 8 animals with incomplete injuries were able to bear weight by 28 days. In vivo magnetic resonance imaging was performed safely, yielded high-resolution images of tissue injury, and correlated closely with injury volume seen on histopathology, which included intramedullary hemorrhage, cellular inflammation, necrosis, and apoptosis.
Piglets performed well as a reproducible model of traumatic pediatric SCI in a large animal with chronic survival and utilizing multiple outcome measures, including evoked potentials, magnetic resonance imaging, functional outcome scores, and histopathology.
建立一种新的、具有临床相关性的小儿脊髓损伤（SCI）大型动物模型，并比较小儿SCI的临床和实验特征。
对3 - 5周龄的幼猪在T7水平通过可控皮质撞击器造成挫伤性SCI。6只幼猪诱导产生严重完全性SCI，定义为感觉运动功能无自发恢复的SCI。8只幼猪接受不完全性SCI，随后部分恢复。在28天的生存期内测量体感诱发电位、磁共振成像、神经行为功能和组织病理学。
与不完全性SCI相比，完全性SCI后平均SCI体积（定义为坏死组织体积）更大（分别为387±29 vs 77±38 mm3，P < 0.001）。完全性SCI后无功能恢复。不完全性SCI后，幼猪最初表现为下肢感觉运动功能缺失、大小便潴留，且几乎没有直肠张力。感觉反应首先恢复（损伤后1 - 2天），随后是自主排尿、下肢运动反应、规律排便以及爬行时下肢的重复屈伸。尽管8只不完全损伤动物中有4只在28天时能够承重，但没有幼猪恢复自主行走。体内磁共振成像安全可行，能产生组织损伤的高分辨率图像，且与组织病理学所见的损伤体积密切相关，组织病理学表现包括脊髓内出血、细胞炎症、坏死和凋亡。
在大型动物中，幼猪作为创伤性小儿SCI的可重复模型表现良好，具有长期生存能力，并可利用多种结局指标，包括诱发电位、磁共振成像、功能结局评分和组织病理学。
