Adelson P D, Robichaud P, Hamilton R L, Kochanek P M
Department of Pediatric Neurosurgery, Children's Hospital of Pittsburgh, Pennsylvania, USA.
J Neurosurg. 1996 Nov;85(5):877-84. doi: 10.3171/jns.1996.85.5.0877.
Diffuse cerebral swelling after severe traumatic brain injury (TBI) develops more commonly in children than adults; however, models of diffuse brain injury in immature animals are lacking. The authors developed a new model of diffuse severe TBI in immature rats by modifying a recently described closed head injury model for adult rats. A total of 105 Sprague-Dawley immature rats (17 days old; average weight 38.5 +/- 5.46 g) were subjected to head impact using variable weights (0 g (sham), 75 g, 100 g, or 125 g) delivered from a height of 2 m onto a metal disk cemented to the intact cranium. Mortality, physiological and neurological parameters (from early reflex recovery to escape), and early histopathological changes were assessed. During the acute period after severe injury (SI) (100 g delivered from a height of 2 m; 50 rats), apnea was frequently observed and the mortality rate was 38%. Neurological recovery was complete in the sham-injured animals (11 rats) by 4.1 +/- 0.23 minutes (mean +/- standard error of the mean), but was delayed in both moderately injured (MI) (75 g/2 m; 11 rats) (14.97 +/- 3.99 minutes) and SI (20.57 +/- 1.31 minutes (p < 0.05)) rats. In the first 24 hours, the sham-injured animals were more active than the injured ones as reflected by a greater net weight gain: 2.9 +/- 1.0 g, 1.2 +/- 1.6 g, and -0.6 +/- 2.1 g in sham-injured, MI, and SI animals, respectively. Immediately after injury, transient hypertension (lasting < 15 seconds) was followed by hypotension (lasting < 3 minutes) and loss of temperature regulation. Both injuries also induced apnea (0.75 +/- 0.7 minutes and 1.27 +/- 0.53 minutes in MI and SI groups, respectively), which either resolved or deteriorated to death. Intubation and assisted ventilation in animals with SI for 9.57 +/- 3.27 minutes in the peritrauma period eliminated mortality (p < 0.05, intubated vs. nonintubated). Histologically, after SI, there was diffuse edema throughout the corpus callosum below the region of injury and in the thalami. Other injuries included neuronal death in the deep nuclei, bilateral disruption of CA3, diffuse subarachnoid hemorrhage, and, in some, ventriculomegaly. Following a diffuse TBI in immature rats, SI produced a mortality rate, neurological deficit, and histological changes similar to those previously reported for an injury resulting from a 450-g weight dropped from 2 m in adult rats. A graded insult was achieved by maintaining the height of the weight drop but varying the weights. Weight loss, acute physiological instability, and acute neurological deficits were also indicative of an SI. Mortality was eliminated when ventilatory support was used during the peritrauma period. This model should be useful in studying the response of the immature rat to diffuse severe TBI.
严重创伤性脑损伤（TBI）后弥漫性脑肿胀在儿童中比成人更常见；然而，缺乏未成熟动物弥漫性脑损伤的模型。作者通过修改最近描述的成年大鼠闭合性颅脑损伤模型，开发了一种新的未成熟大鼠弥漫性重度TBI模型。总共105只Sprague-Dawley未成熟大鼠（17日龄；平均体重38.5±5.46 g），使用可变重量（0 g（假手术）、75 g、100 g或125 g）从2 m高度撞击固定在完整颅骨上的金属盘。评估死亡率、生理和神经学参数（从早期反射恢复到逃避）以及早期组织病理学变化。在重度损伤（SI）（从2 m高度施加100 g；50只大鼠）后的急性期，频繁观察到呼吸暂停，死亡率为38%。假手术组（11只大鼠）的神经功能恢复在4.1±0.23分钟（平均值±平均标准误差）时完成，但中度损伤（MI）组（75 g/2 m；11只大鼠）（14.97±3.99分钟）和SI组（20.57±1.31分钟（p<0.05））均延迟。在最初24小时内，假手术组动物比损伤组更活跃，这表现为净体重增加更多：假手术组、MI组和SI组分别为2.9±1.0 g、1.2±1.6 g和 -0.6±2.1 g。损伤后立即出现短暂高血压（持续<15秒），随后是低血压（持续<3分钟）和体温调节丧失。两种损伤还均诱发了呼吸暂停（MI组和SI组分别为0.75±0.7分钟和1.27±0.53分钟），呼吸暂停要么缓解，要么恶化为死亡。在创伤周围期对SI组动物进行9.57±3.27分钟的插管和辅助通气可消除死亡率（p<0.05，插管组与未插管组相比）。组织学上，SI后，在损伤区域下方的胼胝体和丘脑中存在弥漫性水肿。其他损伤包括深核神经元死亡、CA3双侧破坏、弥漫性蛛网膜下腔出血，部分还包括脑室扩大。在未成熟大鼠发生弥漫性TBI后，SI产生的死亡率、神经功能缺损和组织学变化与先前报道的成年大鼠从2 m高度掉落450 g重物所致损伤相似。通过保持重物掉落高度但改变重量实现了分级损伤。体重减轻、急性生理不稳定和急性神经功能缺损也提示为重度损伤。在创伤周围期使用通气支持可消除死亡率。该模型应有助于研究未成熟大鼠对弥漫性重度TBI的反应。
