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小儿和青少年大鼠创伤性脑损伤的中线(中央)流体冲击模型

Midline (central) fluid percussion model of traumatic brain injury in pediatric and adolescent rats.

作者信息

Rowe Rachel K, Harrison Jordan L, Ellis Timothy W, Adelson P David, Lifshitz Jonathan

机构信息

1Barrow Neurological Institute at Phoenix Children's Hospital.

3Phoenix Veteran Affairs Healthcare System, Phoenix.

出版信息

J Neurosurg Pediatr. 2018 Jul;22(1):22-30. doi: 10.3171/2018.1.PEDS17449. Epub 2018 Apr 20.

Abstract

OBJECTIVE Experimental traumatic brain injury (TBI) models hold significant validity to the human condition, with each model replicating a subset of clinical features and symptoms. TBI is the leading cause of mortality and morbidity in children and teenagers; thus, it is critical to develop preclinical models of these ages to test emerging treatments. Midline fluid percussion injury (FPI) might best represent mild and diffuse clinical brain injury because of the acute behavioral deficits, the late onset of behavioral morbidities, and the absence of gross histopathology. In this study, the authors sought to adapt a midline FPI to postnatal day (PND) 17 and 35 rats. The authors hypothesized that scaling the craniectomy size based on skull dimensions would result in a reproducible injury comparable to the standard midline FPI in adult rats. METHODS PND17 and PND35 rat skulls were measured, and trephines were scaled based on skull size. Custom trephines were made. Rats arrived on PND10 and were randomly assigned to one of 3 cohorts: PND17, PND35, and 2 months old. Rats were subjected to midline FPI, and the acute injury was characterized. The right reflex was recorded, injury-induced apnea was measured, injury-induced seizure was noted, and the brains were immediately examined for hematoma. RESULTS The authors' hypothesis was supported; scaling the trephines based on skull size led to a reproducible injury in the PND17 and PND35 rats that was comparable to the injury in a standard 2-month-old adult rat. The midline FPI suppressed the righting reflex in both the PND17 and PND35 rats. The injury induced apnea in PND17 rats that lasted significantly longer than that in PND35 and 2-month-old rats. The injury also induced seizures in 73% of PND17 rats compared with 9% of PND35 rats and 0% of 2-month-old rats. There was also a significant relationship between the righting reflex time and presence of seizure. Both PND17 and PND35 rats had visible hematomas with an intact dura, indicative of diffuse injury comparable to the injury observed in 2-month-old rats. CONCLUSIONS With these procedures, it becomes possible to generate brain-injured juvenile rats (pediatric [PND17] and adolescent [PND35]) for studies of injury-induced pathophysiology and behavioral deficits, for which rational therapeutic interventions can be implemented.

摘要

目的 实验性创伤性脑损伤(TBI)模型对人类情况具有显著的有效性,每种模型都复制了一部分临床特征和症状。TBI是儿童和青少年死亡和发病的主要原因;因此,开发这些年龄段的临床前模型以测试新出现的治疗方法至关重要。中线流体冲击伤(FPI)可能最能代表轻度和弥漫性临床脑损伤,因为其具有急性行为缺陷、行为发病率的延迟发作以及缺乏明显的组织病理学改变。在本研究中,作者试图将中线FPI应用于出生后第17天(PND17)和第35天(PND35)的大鼠。作者假设根据颅骨尺寸调整颅骨切除术的大小将导致可重复的损伤,类似于成年大鼠的标准中线FPI。方法 测量PND17和PND35大鼠的颅骨,并根据颅骨大小调整环钻尺寸。制作定制环钻。大鼠在PND10到达并随机分配到3个队列之一:PND17、PND35和2个月大。对大鼠进行中线FPI,并对急性损伤进行特征描述。记录右侧反射,测量损伤诱导的呼吸暂停,记录损伤诱导的癫痫发作,并立即检查大脑是否有血肿。结果 作者的假设得到支持;根据颅骨大小调整环钻尺寸导致PND17和PND35大鼠出现可重复的损伤,与标准2个月大大鼠的损伤相当。中线FPI抑制了PND17和PND35大鼠的翻正反射。损伤诱导PND17大鼠出现呼吸暂停,其持续时间明显长于PND35和2个月大大鼠。损伤还诱导73%的PND17大鼠出现癫痫发作,而PND35大鼠为9%,2个月大大鼠为0%。翻正反射时间与癫痫发作的存在之间也存在显著关系。PND17和PND35大鼠均有可见血肿且硬脑膜完整,表明存在与2个月大大鼠观察到的损伤相当的弥漫性损伤。结论 通过这些程序,有可能生成脑损伤的幼年大鼠(儿科[PND17]和青少年[PND35]),用于研究损伤诱导的病理生理学和行为缺陷,从而可以实施合理的治疗干预措施。

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