模拟高原条件下大鼠开放性及爆炸性颅脑损伤模型的建立及伤情特点的初步研究
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摘要
目的：建立模拟高原条件下大鼠开放性及爆炸性颅脑损伤的实验模型，探讨模拟高原颅脑战伤伤情特点，为高原颅脑战伤救治提供实验依据。
方法：（1）通过民用射钉枪射击建立大鼠开放性颅脑损伤的模型；（2）通过在金属密闭环境中军用雷管空中爆炸建立大鼠爆炸性颅脑损伤模型；（3）通过低压氧舱模拟高原条件，并与正常平原环境条件下对照，观察上述两种模型的伤情特点；（4）观察两种模型伤后即刻脑干听觉诱发电位和伤后1h、6h、12h、24h、48h、72h和168h各时相点的脑含水量、伊文氏蓝含量、病理学的改变，了解伤情变化；（5）应用Moor DRT4激光多普勒血流监测仪和LICOX CMP组织氧监测仪进行局部脑血流量和局部脑组织氧分压动态监测，了解两种模型伤情变化特点。(6)应用墨汁灌注和图像分析的方法，观察模型伤后微循环的改变。
结果：（1）本实验条件下所制备的大鼠开放性及爆炸性颅脑损伤模型，伤情稳定，可重复性好；（2）大鼠开放性及爆炸性颅脑损伤模型伤后，均出现不同程度神经功能障碍，且伤后即刻及1h内死亡率最高；高原组与平原组相比，伤情较重，爆炸性颅脑损伤模型中，伤后即刻呼吸暂停发生率明显高于平原组；（3）脑干听觉诱发电位各波潜伏期伤后较伤前有明显延长，高原与平原对照组之间无明显差异，但伤后高原组较平原组各波潜伏期有明显延长；（4）脑含水量、伊文氏蓝含量在伤后1h即出现明显增加，24－48h达到高峰，72h开始恢复，到168h尚未完全恢复正常；高原对照组与平原对照组相比，无差异，两组伤后变化规律基本一致，但伤后6－72h，高原组脑含水量和伊文氏蓝含量较平原组明显增高。（5）局部脑血流量于伤后1h开始明显下降，在伤后48－72h下降到最低点，之后开始恢复，到168h仍未完全恢复正常；高原对照组与平原对照组相比，局部脑血流量明显较高，在伤后1h，高原组局部脑血流量仍明显高于平原组，12－72h则明显低于平原组各时相点；（6）局部脑组织氧分压于伤后1h开始明显下降，在伤后24－48h下降到最低，之后开始恢复；高原对照组与平原对照组相比，局部脑组织氧分压无明显差异，在伤后1h仍无明显差异，在伤后6－72h高原组则明显低于平原组；（7）相关性分析显示，伤后局部脑组织氧分压、局部脑血流量的动态变化与脑含水量的动态变化之间有密切相关关系；（8）病理形态学观察显示，
伤区边缘3mm处，伤后1－6h即有神经细胞缺血性改变，胞浆内尼氏体减少，线粒体肿胀，胞体周围间隙赠宽，血管周围水肿，内皮细胞吞饮小泡增多；到24－48h，上述变化进一步加重，神经细胞出现坏死；72h后开始逐渐恢复；高原组与平原组相比，伤后各相应时相点，病变更为明显。（9）墨汁灌注及图像分析显示，墨汁染色的毛细血管数量在伤后1h即开始减少，到24－48h达到最少，到168h均未完全恢复正常；高原组各时相点毛细血管数量减少幅度大于平原组各相应时相点。
结论：1、通过民用射钉枪射击和军用雷管在金属密闭环境中空中爆炸致伤，并结合低压氧舱持续减压，可以成功建立模拟高原条件下大鼠低速低能投射物所致的开放性及爆炸性颅脑损伤模型。2、本实验两种颅脑损伤模型中，伤后脑水肿以血管源性脑水肿为主，且于伤后早期出现，进行性加重，12－48h达高峰，72h后开始恢复，模拟高原条件下两种模型脑水肿进展规律与平原基本一致，但均较平原程度为重，发展快，且持续时间长。3、与平原对照组相比，高原缺氧对照组大鼠局部脑组织氧分压无明显变化，但局部脑血流量明显增加；模拟高原条件下开放性和爆炸性颅脑损伤伤后伤区局部脑组织缺氧和脑血流量下降更为严重、持续时间更长，表明PbtO2和rCBF监测能较好的反映颅脑损伤后缺血缺氧状态，尤其在高原缺氧环境下更具有特殊重要意义。
Objective: The models of open craniocerebral injury and explosive craniocerebral injury at simulated high altitude in rats were established and the characteristics of those craniocerebral injury models were investigated.
Methods: (1) There were 200 rats in the open craniocerebral injury group and 210 rats in the explosive craniocerebral injury group. The animals were randomly divided into plain group and high altitude group. The open craniocerebral injury model in rats were established with a nailer gun shoot in rat head. The explosive craniocerebral injury model in rats were established with the explosion of detonator in an airtight metal chamber. Simulated high altitude conditions were established with a hypobaric chamber. (2) The brainstem auditory evoked potential after injury, brain water contents, Evans blue contents, and pathology in the two models at 1h, 6h, 12h, 24h, 48h, 72h and 168h after craniocerebral injury were regularly observed. (3) The regional cerebral blood flow (rCBF) and partial pressure of brain tissue oxygen (PbtO2) in the two models at the same time point above mentioned after craniocerebral injury were monitored respectively with Moor DRT4 laser doppler flowmetry and LICOX CMP instrument.
Results: (1) The open craniocerebral injury and explosive craniocerebral injury models in rats were stable. (2) After the injury, there were some neurologic impairments and the higher death rates at the injury moment and at 1h after injury. The rates in high altitude group were higher than that in plain group. The incidence rate of apnea after explosive injury in high altitude group was higher than that in plain group. (3) The peak latencies and interpeak latencies of brainstem auditory evoked potential after injuries were significantly prolonged, and the value in high altitude group after injury were prolonged more significantly than that in plain group. (4) Brain water contents and Evans blue contents were increased immediately at 1h after injury, were maximized during 24-48h, began to restore at 72h , and couldn't return to the control level by 168h after injury.Brain water contents and Evans blue contents after injury in high altitude group were higher than those in plain group. (5)rCBF were decreased significantly at 1h after injury, were minimized during 48-72h afer injury, then began to restore , and couldn't return to the
control level by 168h after injury. The rCBF in high altitude group after injury were decreased more remarkably than that in plain group. (6) PbtO2 were decreased significantly at 1h after injury, were minimized during 24-48h after injury, then began to restore; The PbtO2 in high altitude group during 6-72h after injury were significantly lower than that in plain group. (7) The results of pathological change showed that , at the periphery of 3mm away from the lesion center, there were brain tissue ischemic changes during 1-6h after injury.The Nissl body decreased, mitochondrion swelling, slight increase of perivascular space, and edema of perivascular could be observed. By 24-48h, the changes above mentioned progressed, and from 72h after injury, began to restore. Compared with plain group , the pathologic changes in high altitude group were more obvious . (8) Light microscopy of Chinese ink-injected and image analysis showed , capillary density were decreased at 1h after injury, by 24-48h were minimized, and couldn't return to the control level by 168h after injury; the capillary density were more significantly reduced in high altitude group than that in plain group.
Conclusions: (1) Using nailer gun shoot and the explosion of detonator in an airtight metal chamber and with a hypobaric chamber, the open craniocerebral injury and explosive craniocerebral injury models at simulated high altitude in rats can be establish successfully. (2) The results from our two models indicated that the brain edema were mainly vasogenic edema , exsited during early period after injury, and the brain edema progressed with time, began to restore at 72h after injury. After injury, t
方法：（1）通过民用射钉枪射击建立大鼠开放性颅脑损伤的模型；（2）通过在金属密闭环境中军用雷管空中爆炸建立大鼠爆炸性颅脑损伤模型；（3）通过低压氧舱模拟高原条件，并与正常平原环境条件下对照，观察上述两种模型的伤情特点；（4）观察两种模型伤后即刻脑干听觉诱发电位和伤后1h、6h、12h、24h、48h、72h和168h各时相点的脑含水量、伊文氏蓝含量、病理学的改变，了解伤情变化；（5）应用Moor DRT4激光多普勒血流监测仪和LICOX CMP组织氧监测仪进行局部脑血流量和局部脑组织氧分压动态监测，了解两种模型伤情变化特点。(6)应用墨汁灌注和图像分析的方法，观察模型伤后微循环的改变。
结果：（1）本实验条件下所制备的大鼠开放性及爆炸性颅脑损伤模型，伤情稳定，可重复性好；（2）大鼠开放性及爆炸性颅脑损伤模型伤后，均出现不同程度神经功能障碍，且伤后即刻及1h内死亡率最高；高原组与平原组相比，伤情较重，爆炸性颅脑损伤模型中，伤后即刻呼吸暂停发生率明显高于平原组；（3）脑干听觉诱发电位各波潜伏期伤后较伤前有明显延长，高原与平原对照组之间无明显差异，但伤后高原组较平原组各波潜伏期有明显延长；（4）脑含水量、伊文氏蓝含量在伤后1h即出现明显增加，24－48h达到高峰，72h开始恢复，到168h尚未完全恢复正常；高原对照组与平原对照组相比，无差异，两组伤后变化规律基本一致，但伤后6－72h，高原组脑含水量和伊文氏蓝含量较平原组明显增高。（5）局部脑血流量于伤后1h开始明显下降，在伤后48－72h下降到最低点，之后开始恢复，到168h仍未完全恢复正常；高原对照组与平原对照组相比，局部脑血流量明显较高，在伤后1h，高原组局部脑血流量仍明显高于平原组，12－72h则明显低于平原组各时相点；（6）局部脑组织氧分压于伤后1h开始明显下降，在伤后24－48h下降到最低，之后开始恢复；高原对照组与平原对照组相比，局部脑组织氧分压无明显差异，在伤后1h仍无明显差异，在伤后6－72h高原组则明显低于平原组；（7）相关性分析显示，伤后局部脑组织氧分压、局部脑血流量的动态变化与脑含水量的动态变化之间有密切相关关系；（8）病理形态学观察显示，
伤区边缘3mm处，伤后1－6h即有神经细胞缺血性改变，胞浆内尼氏体减少，线粒体肿胀，胞体周围间隙赠宽，血管周围水肿，内皮细胞吞饮小泡增多；到24－48h，上述变化进一步加重，神经细胞出现坏死；72h后开始逐渐恢复；高原组与平原组相比，伤后各相应时相点，病变更为明显。（9）墨汁灌注及图像分析显示，墨汁染色的毛细血管数量在伤后1h即开始减少，到24－48h达到最少，到168h均未完全恢复正常；高原组各时相点毛细血管数量减少幅度大于平原组各相应时相点。
结论：1、通过民用射钉枪射击和军用雷管在金属密闭环境中空中爆炸致伤，并结合低压氧舱持续减压，可以成功建立模拟高原条件下大鼠低速低能投射物所致的开放性及爆炸性颅脑损伤模型。2、本实验两种颅脑损伤模型中，伤后脑水肿以血管源性脑水肿为主，且于伤后早期出现，进行性加重，12－48h达高峰，72h后开始恢复，模拟高原条件下两种模型脑水肿进展规律与平原基本一致，但均较平原程度为重，发展快，且持续时间长。3、与平原对照组相比，高原缺氧对照组大鼠局部脑组织氧分压无明显变化，但局部脑血流量明显增加；模拟高原条件下开放性和爆炸性颅脑损伤伤后伤区局部脑组织缺氧和脑血流量下降更为严重、持续时间更长，表明PbtO2和rCBF监测能较好的反映颅脑损伤后缺血缺氧状态，尤其在高原缺氧环境下更具有特殊重要意义。
Objective: The models of open craniocerebral injury and explosive craniocerebral injury at simulated high altitude in rats were established and the characteristics of those craniocerebral injury models were investigated.
Methods: (1) There were 200 rats in the open craniocerebral injury group and 210 rats in the explosive craniocerebral injury group. The animals were randomly divided into plain group and high altitude group. The open craniocerebral injury model in rats were established with a nailer gun shoot in rat head. The explosive craniocerebral injury model in rats were established with the explosion of detonator in an airtight metal chamber. Simulated high altitude conditions were established with a hypobaric chamber. (2) The brainstem auditory evoked potential after injury, brain water contents, Evans blue contents, and pathology in the two models at 1h, 6h, 12h, 24h, 48h, 72h and 168h after craniocerebral injury were regularly observed. (3) The regional cerebral blood flow (rCBF) and partial pressure of brain tissue oxygen (PbtO2) in the two models at the same time point above mentioned after craniocerebral injury were monitored respectively with Moor DRT4 laser doppler flowmetry and LICOX CMP instrument.
Results: (1) The open craniocerebral injury and explosive craniocerebral injury models in rats were stable. (2) After the injury, there were some neurologic impairments and the higher death rates at the injury moment and at 1h after injury. The rates in high altitude group were higher than that in plain group. The incidence rate of apnea after explosive injury in high altitude group was higher than that in plain group. (3) The peak latencies and interpeak latencies of brainstem auditory evoked potential after injuries were significantly prolonged, and the value in high altitude group after injury were prolonged more significantly than that in plain group. (4) Brain water contents and Evans blue contents were increased immediately at 1h after injury, were maximized during 24-48h, began to restore at 72h , and couldn't return to the control level by 168h after injury.Brain water contents and Evans blue contents after injury in high altitude group were higher than those in plain group. (5)rCBF were decreased significantly at 1h after injury, were minimized during 48-72h afer injury, then began to restore , and couldn't return to the
control level by 168h after injury. The rCBF in high altitude group after injury were decreased more remarkably than that in plain group. (6) PbtO2 were decreased significantly at 1h after injury, were minimized during 24-48h after injury, then began to restore; The PbtO2 in high altitude group during 6-72h after injury were significantly lower than that in plain group. (7) The results of pathological change showed that , at the periphery of 3mm away from the lesion center, there were brain tissue ischemic changes during 1-6h after injury.The Nissl body decreased, mitochondrion swelling, slight increase of perivascular space, and edema of perivascular could be observed. By 24-48h, the changes above mentioned progressed, and from 72h after injury, began to restore. Compared with plain group , the pathologic changes in high altitude group were more obvious . (8) Light microscopy of Chinese ink-injected and image analysis showed , capillary density were decreased at 1h after injury, by 24-48h were minimized, and couldn't return to the control level by 168h after injury; the capillary density were more significantly reduced in high altitude group than that in plain group.
Conclusions: (1) Using nailer gun shoot and the explosion of detonator in an airtight metal chamber and with a hypobaric chamber, the open craniocerebral injury and explosive craniocerebral injury models at simulated high altitude in rats can be establish successfully. (2) The results from our two models indicated that the brain edema were mainly vasogenic edema , exsited during early period after injury, and the brain edema progressed with time, began to restore at 72h after injury. After injury, t
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46. Lassen NA, Harper AM. High altitude cerebral edema. Lancet, 1975, 6:1154
47. Yarnell PR， Heit J, Hackett，PH. High-altitude cerebral edema (HACE): the Denver/Front Range experience. Semin Neurol. 2000; 20(2): 209-17
48. Watanabe H， Kuwabara T， Ohkubo-M, et al. Visualization of brain function using MRI-MR functional brain imaging No To Shinkei. 1993 Oct; 45(10): 941-4
Frahm J, Bruhn H, Merboldt-KD, et al. Dynamic MR imaging of human brain
49. oxygenation during rest and photic stimulation. J Magn Reson Imaging. 1992 Sep-Oct; 2(5): 501-5
50. Buunk G, van der Hoeven JG, Meinders AE. A comparison of near-infrared spectroscopy and jugular bulb oximetry in comatose patients resuscitated from a cardiac arrest. Anaesthesia. 1998 Jan; 53(1): 13-9
51. Fandino J, Stocker R, Prokop S, et al. Correlation between jugular bulb oxygen saturation and partial pressure of brain tissue oxygen during CO2 and O2 reactivity tests in severely head-injured patients. Imhof HG Acta Neurochir Wien. 1999; 141(8): 825-34
52. Smythe PR, Samra SK. Monitors of cerebral oxygenation. Anesthesiol Clin North America. 2002 Jun; 20(2): 293-313.
53. Haberl RL, Villringer A, Dirnagl U. Applicability of laser-Doppler flowmetry for cerebral blood flow monitoring in neurological intensive care. Acta Neurochir Suppl (Wien). 1993; 59: 64-8.
54. Wilander Ｌ,Rundquist I, Oberg PA.. Laser He//Ne light exposure of red blood cells. Med Biol Eng Comput.1986, 24 :558-560
55. van den Brink WA, van Santbrink H, Steyerberg EW, et al. Brain oxygen tension in severe head injury. Neurosurgery. 2000 Apr; 46(4): 868-76; discussion 876-8
56. Unterberg-AW; Kiening-KL; Hartl-R, et al. Multimodal monitoring in patients with head injury: evaluation of the effects of treatment on cerebral oxygenation. J-Trauma. 1997 May; 42(5 Suppl): S32-7
57. Robertson CS, Gopinath SP, Goodman JC, et al. SjvO2 monitoring in head-injured patients. J Neurotrauma. 1995 Oct; 12(5): 891-6.
58. Valadka AB, Gopinath SP, Contant CF, et al. Relationship of brain tissue PO2 to outcome after severe head injury. Crit Care Med. 1998 Sep; 26(9): 1576-81
59. Titovets E, Nechipurenko N, Griboedova T, et al. Experimental study on brain oxygenation in relation to tissue water redistribution and brain oedema. Acta Neurochir Suppl. 2000; 76: 279-81
60. Oertel M, Kelly DF, Lee JH, et al. Metabolic suppressive therapy as a treatment for intracranial hypertension--why it works and when it fails. Acta Neurochir Suppl. 2002; 81: 69-70.
Liu H, Goodman JC, Robertson CS. The effects of L-arginine on cerebral hemodynamics after controlled cortical impact injury in the mouse. J Neurotrauma.
61. 2002 Mar; 19(3): 327-34.
62. Cherian L, Chacko G, Goodman JC, et al. Cerebral hemodynamic effects of phenylephrine and L-arginine after cortical impact injury. Crit-Care-Med.1999 Nov; 27(11): 2512-7.
63. Hudetz AG，Biswal BB, Shen H, et al. Spontaneous fluctuations in cerebral oxygen supply. An introduction. Adv Exp Med Biol.1998; 454: 551-9.
64. Long JB, Gordon J, Bettencourt JA, et al. Laser-Doppler flowmetry measurements of subcortical blood flow changes after fluid percussion brain injury in rats. J Neurotrauma. 1996 Mar; 13(3): 149-62.
65. Grande,-P-O; Moller,-A-D; Nordstrom,-C-H; et al. Low-dose prostacyclin in treatment of severe brain trauma evaluated with microdialysis and jugular bulb oxygen measurements. Acta-Anaesthesiol-Scand. 2000 Aug; 44(7): 886-94
66. Allen-GV; Gerami-D; Esser-MJ. Conditioning effects of repetitive mild neurotrauma on motor function in an animal model of focal brain injury. Neuroscience. 2000; 99(1): 93-105
67. Dore-Duffy-P; Owen-C; Balabanov-R; et al. Pericyte migration from the vascular wall in response to traumatic brain injury. Microvasc-Res. 2000 Jul; 60(1): 55-69
68. Vannucci RC. Cerebral carbohydrate and energy metabolism in perinatal hypoxic-ischemic brain damage. Brain-Pathol. 1992 Jul; 2(3): 229-34.
69. Wolff CB. Cerebral blood flow and oxygen delivery at high altitude. High Alt Med Biol. 2000 Spring; 1(1): 33-8
70. Severinghaus JW, Chiodi H, Eger EI, and et al. Cerebral blood flow in man at high altitude. Role of cerebrospinal fluid pH in normalization of flow in chronic hypocapnia. Circ-Res.1966 Aug; 19(2): 274-82.
71. Jansen GF, Krins A, Basnyat B. Cerebral vasomotor reactivity at high altitude in humans. J Appl Physiol. 1999 Feb; 86(2): 681-6
72. Jensen JB, Sperling B, Severinghaus JW, et al. Augmented hypoxic cerebral vasodilation in men during 5 days at 3,810 m altitude. J Appl Physiol. 1996 Apr; 80(4): 1214-8
73. Hackett PH. High altitude cerebral edema and acute mountain sickness. A pathophysiology update. Adv Exp Med Biol. 1999; 474: 23-45
74. Valadka AB，Hlatky R，Furuya Y，et al. Brain tissue PO2: correlation with cerebral blood flow. Acta Neurochir Suppl. 2002; 81: 299-301.
75. Burger R, Vince GH, Meixensberger J,et al. Bilateral monitoring of CBF and tissue oxygen pressure in the penumbra of a focal mass lesion in rats. Acta Neurochir Suppl (Wien). 1998; 71: 157-61.
76. Scatkowski M, Attwell D. Triggering and excution of neuronal death in brain ischemia: two phases of glutamate release by different mechanisms. Trends Neurosci, 1994, 17:359
77. Zauner Alois, Daugherty WilsonP, Bullock Mross, et al. Brain oxygenation and energy metabolism: part I-biological function and pathophysiology. Neurosurgery. 2002 Aug; 51(2): 289-301; discussion 302.
78. Rocca M, Giavaresi G, Fini M, et al. Laser Doppler evaluation of microcirculation behaviour during an ischaemia reperfusion injury. Eur Surg Res. 1998; 30(2): 108-14.
79. Kiening KL, Hartl R, Unterberg AW，et al. Brain tissue pO2-monitoring in comatose patients: implications for therapy. Neurol Res, 1997 Jun; 19(3): 233-40.
80. Imberti Roberto, Bellinzona Guido, Langer Martin. Cerebral tissue PO2 and SjvO2 changes during moderate hyperventilation in patients with severe traumatic brain injury. J Neurosurg. 2002 Jan; 96(1): 97-102.
81. Lee JH, Kelly DF, Oertel M, et al. Carbon dioxide reactivity, pressure autoregulation, and metabolic suppression reactivity after head injury: a transcranial Doppler study. J Neurosurg. 2001 Aug; 95(2): 222-32.
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45. Kimelberg HC. Current concepts of brain edema. J Neurosurg, 1995; 83(12): 1051
46. Lassen NA, Harper AM. High altitude cerebral edema. Lancet, 1975, 6:1154
47. Yarnell PR， Heit J, Hackett，PH. High-altitude cerebral edema (HACE): the Denver/Front Range experience. Semin Neurol. 2000; 20(2): 209-17
48. Watanabe H， Kuwabara T， Ohkubo-M, et al. Visualization of brain function using MRI-MR functional brain imaging No To Shinkei. 1993 Oct; 45(10): 941-4
Frahm J, Bruhn H, Merboldt-KD, et al. Dynamic MR imaging of human brain
49. oxygenation during rest and photic stimulation. J Magn Reson Imaging. 1992 Sep-Oct; 2(5): 501-5
50. Buunk G, van der Hoeven JG, Meinders AE. A comparison of near-infrared spectroscopy and jugular bulb oximetry in comatose patients resuscitated from a cardiac arrest. Anaesthesia. 1998 Jan; 53(1): 13-9
51. Fandino J, Stocker R, Prokop S, et al. Correlation between jugular bulb oxygen saturation and partial pressure of brain tissue oxygen during CO2 and O2 reactivity tests in severely head-injured patients. Imhof HG Acta Neurochir Wien. 1999; 141(8): 825-34
52. Smythe PR, Samra SK. Monitors of cerebral oxygenation. Anesthesiol Clin North America. 2002 Jun; 20(2): 293-313.
53. Haberl RL, Villringer A, Dirnagl U. Applicability of laser-Doppler flowmetry for cerebral blood flow monitoring in neurological intensive care. Acta Neurochir Suppl (Wien). 1993; 59: 64-8.
54. Wilander Ｌ,Rundquist I, Oberg PA.. Laser He//Ne light exposure of red blood cells. Med Biol Eng Comput.1986, 24 :558-560
55. van den Brink WA, van Santbrink H, Steyerberg EW, et al. Brain oxygen tension in severe head injury. Neurosurgery. 2000 Apr; 46(4): 868-76; discussion 876-8
56. Unterberg-AW; Kiening-KL; Hartl-R, et al. Multimodal monitoring in patients with head injury: evaluation of the effects of treatment on cerebral oxygenation. J-Trauma. 1997 May; 42(5 Suppl): S32-7
57. Robertson CS, Gopinath SP, Goodman JC, et al. SjvO2 monitoring in head-injured patients. J Neurotrauma. 1995 Oct; 12(5): 891-6.
58. Valadka AB, Gopinath SP, Contant CF, et al. Relationship of brain tissue PO2 to outcome after severe head injury. Crit Care Med. 1998 Sep; 26(9): 1576-81
59. Titovets E, Nechipurenko N, Griboedova T, et al. Experimental study on brain oxygenation in relation to tissue water redistribution and brain oedema. Acta Neurochir Suppl. 2000; 76: 279-81
60. Oertel M, Kelly DF, Lee JH, et al. Metabolic suppressive therapy as a treatment for intracranial hypertension--why it works and when it fails. Acta Neurochir Suppl. 2002; 81: 69-70.
Liu H, Goodman JC, Robertson CS. The effects of L-arginine on cerebral hemodynamics after controlled cortical impact injury in the mouse. J Neurotrauma.
61. 2002 Mar; 19(3): 327-34.
62. Cherian L, Chacko G, Goodman JC, et al. Cerebral hemodynamic effects of phenylephrine and L-arginine after cortical impact injury. Crit-Care-Med.1999 Nov; 27(11): 2512-7.
63. Hudetz AG，Biswal BB, Shen H, et al. Spontaneous fluctuations in cerebral oxygen supply. An introduction. Adv Exp Med Biol.1998; 454: 551-9.
64. Long JB, Gordon J, Bettencourt JA, et al. Laser-Doppler flowmetry measurements of subcortical blood flow changes after fluid percussion brain injury in rats. J Neurotrauma. 1996 Mar; 13(3): 149-62.
65. Grande,-P-O; Moller,-A-D; Nordstrom,-C-H; et al. Low-dose prostacyclin in treatment of severe brain trauma evaluated with microdialysis and jugular bulb oxygen measurements. Acta-Anaesthesiol-Scand. 2000 Aug; 44(7): 886-94
66. Allen-GV; Gerami-D; Esser-MJ. Conditioning effects of repetitive mild neurotrauma on motor function in an animal model of focal brain injury. Neuroscience. 2000; 99(1): 93-105
67. Dore-Duffy-P; Owen-C; Balabanov-R; et al. Pericyte migration from the vascular wall in response to traumatic brain injury. Microvasc-Res. 2000 Jul; 60(1): 55-69
68. Vannucci RC. Cerebral carbohydrate and energy metabolism in perinatal hypoxic-ischemic brain damage. Brain-Pathol. 1992 Jul; 2(3): 229-34.
69. Wolff CB. Cerebral blood flow and oxygen delivery at high altitude. High Alt Med Biol. 2000 Spring; 1(1): 33-8
70. Severinghaus JW, Chiodi H, Eger EI, and et al. Cerebral blood flow in man at high altitude. Role of cerebrospinal fluid pH in normalization of flow in chronic hypocapnia. Circ-Res.1966 Aug; 19(2): 274-82.
71. Jansen GF, Krins A, Basnyat B. Cerebral vasomotor reactivity at high altitude in humans. J Appl Physiol. 1999 Feb; 86(2): 681-6
72. Jensen JB, Sperling B, Severinghaus JW, et al. Augmented hypoxic cerebral vasodilation in men during 5 days at 3,810 m altitude. J Appl Physiol. 1996 Apr; 80(4): 1214-8
73. Hackett PH. High altitude cerebral edema and acute mountain sickness. A pathophysiology update. Adv Exp Med Biol. 1999; 474: 23-45
74. Valadka AB，Hlatky R，Furuya Y，et al. Brain tissue PO2: correlation with cerebral blood flow. Acta Neurochir Suppl. 2002; 81: 299-301.
75. Burger R, Vince GH, Meixensberger J,et al. Bilateral monitoring of CBF and tissue oxygen pressure in the penumbra of a focal mass lesion in rats. Acta Neurochir Suppl (Wien). 1998; 71: 157-61.
76. Scatkowski M, Attwell D. Triggering and excution of neuronal death in brain ischemia: two phases of glutamate release by different mechanisms. Trends Neurosci, 1994, 17:359
77. Zauner Alois, Daugherty WilsonP, Bullock Mross, et al. Brain oxygenation and energy metabolism: part I-biological function and pathophysiology. Neurosurgery. 2002 Aug; 51(2): 289-301; discussion 302.
78. Rocca M, Giavaresi G, Fini M, et al. Laser Doppler evaluation of microcirculation behaviour during an ischaemia reperfusion injury. Eur Surg Res. 1998; 30(2): 108-14.
79. Kiening KL, Hartl R, Unterberg AW，et al. Brain tissue pO2-monitoring in comatose patients: implications for therapy. Neurol Res, 1997 Jun; 19(3): 233-40.
80. Imberti Roberto, Bellinzona Guido, Langer Martin. Cerebral tissue PO2 and SjvO2 changes during moderate hyperventilation in patients with severe traumatic brain injury. J Neurosurg. 2002 Jan; 96(1): 97-102.
81. Lee JH, Kelly DF, Oertel M, et al. Carbon dioxide reactivity, pressure autoregulation, and metabolic suppression reactivity after head injury: a transcranial Doppler study. J Neurosurg. 2001 Aug; 95(2): 222-32.