A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model.
A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model.
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DOI：
10.1016/j.nbd.2021.105334
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发表时间：
2021-07
影响因子：
6.1
通讯作者：
Duhaime AC
中科院分区：
文献类型：
--
作者：
Costine-Bartell B;Price G;Shen J;McGuone D;Staley K;Duhaime AC
半球低密度是一种在幼儿中观察到的严重脑损伤类型，其广泛皮质组织破坏的病理生理学尚不清楚。在这里，我们利用我们独特的具有多因素损伤和侮辱的半球低密度的大型动物模型来了解这种严重类型的创伤性脑损伤的病理生理学，测试不同发育阶段的影响。发育类似于人类婴儿(1周大的“婴儿”)和蹒跚学步的婴儿(1个月大的“蹒跚学步的孩子”)的小猪，在用允许癫痫发作的方法麻醉时，会受到与脑体积成比例的损伤和侮辱：皮质撞击、产生质量效应、放置硬膜下血肿、癫痫发作诱导、呼吸暂停、呼吸不足或假损伤。接受模型损伤的仔猪需要通宵重症监护。通过组织病理学评估大脑半球的损伤。损伤类型与癫痫发作持续时间和出血模式有关，导致损伤同侧为单侧半球，大脑深部区域和对侧大脑半球不受影响。虽然“婴儿”的癫痫发作持续时间与“蹒跚学步的孩子”相同，但损害比“蹒跚学步的孩子”要小，与癫痫发作的持续时间无关，而且像人类婴儿经常观察到的那样，是双侧的和斑驳的。硬膜下出血伴邻侧局灶性蛛网膜下腔出血。大脑半球蛛网膜下腔出血的覆盖率与两个发育阶段的损伤呈正相关。在“婴儿”中，皮质上的出血与皮质损伤有关，但保留了深部灰质区域；如果没有出血，损伤直接指向海马体，皮质则幸免于难。“婴儿”的神经学得分低于“蹒跚学步的孩子”。这种严重脑损伤的多因素模型导致发育类似于幼儿的小猪一侧广泛的皮质破坏，癫痫发作持续时间和覆盖脑部的出血与组织破坏呈正相关。与生俱来的发育差异可能会影响大脑对癫痫发作的反应，从而影响损伤的程度和模式。目前正在对“婴儿”大脑如何抵抗癫痫发作的影响进行具体研究，并可能确定可能减少严重脑创伤后组织损伤演变的潜在治疗靶点。
The pathophysiology of extensive cortical tissue destruction observed in hemispheric hypodensity, a severe type of brain injury observed in young children, is unknown. Here, we utilize our unique, large animal model of hemispheric hypodensity with multifactorial injuries and insults to understand the pathophysiology of this severe type of traumatic brain injury, testing the effect of different stages of development. Piglets developmentally similar to human infants (1 week old, “infants”) and toddlers (1 month old, “toddlers”) underwent injuries and insults scaled to brain volume: cortical impact, creation of mass effect, placement of a subdural hematoma, seizure induction, apnea, and hypoventilation or a sham injury while anesthetized with a seizure-permissive regimen. Piglets receiving model injuries required overnight intensive care. Hemispheres were evaluated for damage via histopathology. The pattern of damage was related to seizure duration and hemorrhage pattern in “toddlers” resulting in a unilateral hemispheric pattern of damage ipsilateral to the injuries with sparing of the deep brain regions and the contralateral hemisphere. While “infants” had the equivalent duration of seizures as “toddlers”, damage was less than “toddlers”, not correlated to seizure duration, and was bilateral and patchy as is often observed in human infants. Subdural hemorrhage was associate with adjacent focal subarachnoid hemorrhage. The percentage of the hemisphere covered with subarachnoid hemorrhage was positively correlated with damage in both developmental stages. In “infants”, hemorrhage over the cortex was associated with damage to the cortex with sparing of the deep gray matter regions; without hemorrhage, damage was directed to the hippocampus and the cortex was spared. “Infants” had lower neurologic scores than “toddlers”. This multifactorial model of severe brain injury caused unilateral, wide-spread destruction of the cortex in piglets developmentally similar to toddlers where both seizure duration and hemorrhage covering the brain were positively correlated to tissue destruction. Inherent developmental differences may affect how the brain responds to seizure, and thus, affects the extent and pattern of damage. Study into specifically how the “infant” brain is resistant to the effects of seizure is currently underway and may identify potential therapeutic targets that may reduce evolution of tissue damage after severe traumatic brain injury.
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影响因子：
26.1
作者：
Berger, Rachel Pardes;Pak, Brian J.;Kochanek, Patrick M.
通讯作者：
Kochanek, Patrick M.
影响因子：
2.9
作者：
Costine BA;Missios S;Taylor SR;McGuone D;Smith CM;Dodge CP;Harris BT;Duhaime AC
通讯作者：
Duhaime AC
影响因子：
2.9
作者：
Goasdoue, Kate;Chand, Kirat Kishore;Bjorkman, Stella Tracey
通讯作者：
Bjorkman, Stella Tracey
影响因子：
4.1
作者：
Duhaime, AC;Margulies, SS;Raghupathi, R
通讯作者：
Raghupathi, R
影响因子：
0.7
作者：
Duhaime, AC;Christian, C;Seidl, T
通讯作者：
Seidl, T