大鼠创伤性脑损伤后慢性血管变化与功能结局的关系。
Association of chronic vascular changes with functional outcome after traumatic brain injury in rats.
机构信息
Department of Neurobiology, Biomedical NMR Group, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
出版信息
J Neurotrauma. 2010 Dec;27(12):2203-19. doi: 10.1089/neu.2010.1448. Epub 2010 Oct 18.
We tested the hypothesis that vascular remodeling in the cortex, hippocampus, and thalamus is associated with long-term functional recovery after traumatic brain injury (TBI). We induced TBI with lateral fluid-percussion (LFP) injury in adult rats. Animals were followed-up for 9 months, during which we tested motor performance using a neuroscore test, spatial learning and memory with a Morris water maze, and seizure susceptibility with a pentylenetetrazol (PTZ) test. At 8 months, they underwent structural MRI, and cerebral blood flow (CBF) was assessed by arterial spin labeling (ASL) MRI. Then, rats were perfused for histology to assess the density of blood vessels. In the perilesional cortex, the CBF decreased by 56% (p < 0.01 compared to controls), and vessel density increased by 28% (p < 0.01). There was a negative correlation between CBF in the perilesional cortex and vessel density (r = -0.75, p < 0.01). However, in the hippocampus, we found a 13% decrease in CBF ipsilaterally (p < 0.05) and 20% contralaterally (p < 0.01), and no change in vessel number. In the ipsilateral thalamus, the increase in CBF (34%, p < 0.01) was associated with a remarkable increase in vessel density (78%, p < 0.01). Animals showed motor impairment that was not associated with vascular changes. Instead, poor performance in the Morris water maze correlated with enhanced thalamic vessel density (r = -0.81, p < 0.01). Finally, enhanced seizure susceptibility was associated with reduced CBF in the ipsilateral hippocampus (r = 0.78, p < 0.05) and increased vascular density in the thalamus (r = 0.69, p < 0.05). There was little interaction between the behavioral measures. The present study demonstrates that each of the investigated brain areas has a unique pattern of vascular abnormalities. Chronic alterations in CBF could not be attributed to changes in vascular density. Association of thalamic hypervascularity to epileptogenesis warrants further studies. Finally, hippocampal hypoperfusion may predict later seizure susceptibility in the LFP injury model of TBI, which could be of value for pre-clinical antiepileptogenesis trials.
我们检验了这样一个假设，即皮质、海马体和丘脑的血管重塑与创伤性脑损伤（TBI）后的长期功能恢复有关。我们通过侧方液压冲击（LFP）损伤诱导成年大鼠的 TBI。动物被随访 9 个月，在此期间，我们使用神经评分测试测试运动表现，使用 Morris 水迷宫测试空间学习和记忆，使用戊四氮（PTZ）测试癫痫易感性。在 8 个月时，它们接受了结构 MRI，并通过动脉自旋标记（ASL）MRI 评估脑血流（CBF）。然后，对大鼠进行灌注以进行组织学评估，以评估血管密度。在损伤周围皮质中，CBF 降低了 56%（与对照组相比，p<0.01），血管密度增加了 28%（p<0.01）。损伤周围皮质中的 CBF 与血管密度呈负相关（r=-0.75，p<0.01）。然而，在海马体中，我们发现同侧 CBF 降低了 13%（p<0.05），对侧降低了 20%（p<0.01），而血管数量没有变化。在同侧丘脑，CBF 增加了 34%（p<0.01），血管密度显著增加了 78%（p<0.01）。动物表现出运动障碍，与血管变化无关。相反，Morris 水迷宫中的不良表现与增强的丘脑血管密度相关（r=-0.81，p<0.01）。最后，增强的癫痫易感性与同侧海马体中 CBF 降低（r=0.78，p<0.05）和丘脑血管密度增加（r=0.69，p<0.05）有关。行为测量之间几乎没有相互作用。本研究表明，每个研究的脑区都有独特的血管异常模式。慢性 CBF 改变不能归因于血管密度的变化。丘脑血管过度增生与癫痫发生的关联需要进一步研究。最后，海马体低灌注可能预测 TBI 的 LFP 损伤模型中以后的癫痫易感性，这可能对临床前抗癫痫发生试验有价值。
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