低氧血症对轻型颅脑损伤大鼠海马结构二次脑损伤的实验研究
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摘要
目的应用低氧血症二次脑损伤大鼠模型,探讨低氧血症对轻型颅脑损伤(mTBI)后海马神经元及轴索组织结构的二次损伤作用。方法采用随机数字表法将大鼠分为正常对照组(8只)、单纯mTBl组(10只)、单纯低氧血症组(10只)及低氧血症二次脑损伤组(10只)。在自制旋转装置致大鼠mTBI基础上,利用动物呼吸机获得控制性低氧血症,从而构建低氧血症二次脑损伤模型。脑损伤后1周,应用HE染色、免疫组化β-APP染色及电镜观察大鼠海马组织结构病理学变化。结果 HE染色发现单纯低氧血症组大鼠海马神经元结构完整、排列有序、神经组织结构致密、未见明显神经元丢失及神经组织结构疏松等病理变化,单纯mTBI组及低氧血症二次脑损伤组大鼠均出现海马神经元肿胀、胞质淡染、密度降低、排列不规则及神经组织结构疏松等损伤表现,但低氧血症二次脑损伤组较单纯mTBI组明显。免疫组化β-APP染色及电镜观察到低氧血症二次脑损伤组大鼠海马存在轴索肿胀扭曲变形、髓鞘板层分离及轴索球形成等轴索损伤表现。结论低氧血症二次脑损伤可明显加重mTBI后海马神经元及轴索组织结构的损伤,及早预防、发现和治疗低氧血症对改善mTBI患者预后具有积极意义。
Objective To investigate the effects of post-traumatic hypoxemia on mild traumatic brain injury(mTBI) in rats.Methods The experimental model was established by instantly rotating 90 degree followed by hypoxemic insult in rats.Animals in group 1 were subjected to primary mTBI and subsequent hypoxemia(n=10);animals in group 2 were subjects to mTBI only(n=10);animals in group 3 underwent hypoxemia only(;;=10) and animals in group 4 served as the controls(n=8).Pathological and behavioral examinations were conducted 1 week after injury.Results All rats in group 2 and 3 survived after mTBI or hypoxemia,whereas 2 animals died in group 1 with a mortality rate of 20.0%.Histological examination of HE-stained sections,electron microscope,and β-APP immunohistochemistry revealed the presence of neuronal and axonal injury in CA3 of hippocampus in rats of group 1.Pathological changes of neuronal injury in group 2 were exhibited,but no additional axonal damage was demonstrated.The above changes were not found in groups 3 and 4.Conclusion The combination of primary mTBI and secondary hypoxemia can cause synergistic effects to produce significantly pathological changes in CA3 of hippocampus in rats.
Objective To investigate the effects of post-traumatic hypoxemia on mild traumatic brain injury(mTBI) in rats.Methods The experimental model was established by instantly rotating 90 degree followed by hypoxemic insult in rats.Animals in group 1 were subjected to primary mTBI and subsequent hypoxemia(n=10);animals in group 2 were subjects to mTBI only(n=10);animals in group 3 underwent hypoxemia only(;;=10) and animals in group 4 served as the controls(n=8).Pathological and behavioral examinations were conducted 1 week after injury.Results All rats in group 2 and 3 survived after mTBI or hypoxemia,whereas 2 animals died in group 1 with a mortality rate of 20.0%.Histological examination of HE-stained sections,electron microscope,and β-APP immunohistochemistry revealed the presence of neuronal and axonal injury in CA3 of hippocampus in rats of group 1.Pathological changes of neuronal injury in group 2 were exhibited,but no additional axonal damage was demonstrated.The above changes were not found in groups 3 and 4.Conclusion The combination of primary mTBI and secondary hypoxemia can cause synergistic effects to produce significantly pathological changes in CA3 of hippocampus in rats.
引文
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[2]Vos P E,Alekseenko Y,Battistin L,et al.Mild traumatic brain injury[J].Eur J Neurol,2012,19(2):191-198.
[3]Mayer A R,Ling J,Mannell M V,et al.A prospective diffusion tensor imaging study in mild traumatic brain injury[J].Neurology,2010,74(8):643-650.
[4]McHugh G S,Engel D C,Butcher I,et al.Prognostic value of secondary insults in traumatic brain injury:results from the IMPACT study[J].J Neurotrauma,2007,24(2):287-293.
[5]Wang H C,Duan Z X,Wu F F,et al.A new rat model for diffuse axonal injury with linear acceleration and angular acceleration combined[J].J Neurotrauma,2010,27(4):707-719.
[6]朱坤灿,王洪财,陈海,等.大鼠低氧血症性二次脑损伤模型的建立[J].中华实验外科杂志,2014,31(10):2332-2334.
[7]Max J E,Schachar R J,Landis J,et al.Psychiatric disorders in children and adolescents in the first six months after mild traumatic brain injury[J].J Neuropsychiatry Clin Neurosci,2013,25(3):187-197.
[8]Maas A I,Marmarou A,Murray G D,et al.Prognosis and clinical trial design in traumatic brain injury:the IMPACT study[J].J Neurotrauma,2007,24(2):232-238.
[9]Kochanek P M,Robert S B C,Larry W J.Pathobiology of Secondary Brain Injury[M]//Nathan D Z,Douglas I K.Ross D Z.2nd edition.Brain Injury Medicine:Principles and Practice.New York:Demos Medical Publishing,2012:148.
[10]Stochetti N,Furlan A,Volta F.Hypoxemia and arterial hypotension at the accident scene in head injury[J].J Trauma,1996,40(5):764-767.
[11]王波定,王洪财,朱坤灿,等.创伤性脑损伤模型的延续与完善:二次脑损伤模型[J]中华神经医学杂志,2013,12(4):426-429
[12]Feng J F,Zhao X,Gurkoff G G,et al.Post-traumatic hypoxia exacerbates neuronal cell death in the hippocampus[J].J Neurotrauma,2012,29(6):1167-1179.
[13]Yan E B,Hellewell S C,Bellander B M,et al.Post-traumatic hypoxia exacerbates neurological deficit,neuroinflammation and cerebral metabolism in rats with diffuse traumatic brain injury[J].J Neuroinflammation,2011,28(8):147-163.
[14]Bauman R A,Widholm J,Long J B.Secondary hypoxia exacerbates acute disruptions of energy metabolism in rats resulting from fluid percussion injury[J].Behav Brain Res,2005,160(1):25-33.
[15]Dolinak D,Smith C,Graham D I.Global hypoxia per se is an unusual cause of axonal injury[J].Acta Neuropathol,2000,100(5):553-560.
[16]Metting Z,Rodiger L A,Stewart R E,et al.Perfusion computed tomography in the acute phase of mild head injury:regional dysfunction and prognostic value[J].Ann Neurol,2009,66(6):809-816.
[17]Prins M L,Alexander D,Giza C C,et al.Repeated mild traumatic brain injury:mechanisms of cerebral vulnerability[J].J Neurotrauma,2013,30(1):30-38.