(二)脑成像研究
核磁共振成像技术为缺氧导致的人类脑损伤提供了直接的观察途径。大量研究采用结构性脑成像技术去探究急性缺氧对人类大脑的影响。不同海拔高度的结果并不一致。Anooshiravani等人(1999)并未发现从海拔6 000 m返回的登山者脑功能和脑结构的异常[27]。但是,Garrido等人(1995)用发现从海拔8 000 m返回的登山者三处脑结构的改变。他们扫描了26名从7 000 m峰顶回到平原的登山者,发现5人有皮质萎缩迹象、5人白质疏松[28]。Griggs和Sutton(1992)的研究中,56%的个体侧脑室旁(白质疏松)、后顶叶、枕叶白质有高强度信号改变[29]。另外一项研究也获得了类似结果,来自低海拔地区的21名登山者在海拔为7 000 m以上地区平均停留445小时,在海拔8 000 m以上地区停留56.5小时。61%的登山者出现了皮质萎缩迹象和高强度信号,这些改变主要发生在顶叶后、侧脑室旁[30]。
对比6名被试在海拔3 181 m和6 157 m处停留63天前后的正电子断层扫描数据发现,额叶、左侧枕叶及右侧丘脑的葡萄糖代谢下降[31]。然而Moller等人(2002)并没有得到这样显著的结果。他们测查了9名低海拔居民在高海拔停留一段时间前后全脑氧、葡萄糖、氧传输和脑血流量的新陈代谢率,发现去高海拔地区前后,在练习和休息两种状态下脑部新陈代谢过程都没有显著差异[32]。在夏尔巴人身上也没有发现Hochachka等人(1999)观察到的改变,夏尔巴人大脑的代谢率和低海拔居民并无差异[33]。
高海拔世居者的神经影像学研究结果也不一致。安第斯山脉世居者(魁北克人)大脑的葡萄糖代谢下降,特别是额叶、顶叶、角回和丘脑,研究者认为代谢下降是为了抵御慢性缺氧[34]。但是生活在西藏的夏尔巴人却没有表现出这样的差异[35]。研究者在喜马拉雅居民[36]和夏尔巴人[37]身上多次观察到大脑自动调整能力的损伤,说明即使经历了几百年的生物选择,人类的适应能力仍然是有限的。Yan等人(2010)对青藏高原地区常住汉族居民的研究发现,高海拔居民的双侧前脑岛、双侧前额叶、左侧中央前回、左侧扣带回和右侧舌回的灰质容量下降[38]。
[1]Moore L G.Comparative human ventilatory adaptation to high altitude[J].Respiration physiology,2000,121(2-3): 257-276.
[2]Virués-Ortega J,Buela-Casal G,Garrido E,et al.Neuropsychological functioning associated with high-altitude exposure[J].Neuropsychology review,2004,14(4):197-224.
[3]Garrido E,Segura R,Capdevila A,et al.Are Himalayan Sherpas better protected against brain damage associated with extreme altitude climbs?[J].Clinical science,1996,90(1): 81-85.
[4]Rodas G,Javierre C,Garrido E,et al.Normoxic ventilatory response in lowlander and Sherpa elite climbers[J].Respiration physiology,1998,113(1): 57-64.
[5]Rodas G,Javierre C,Garrido E,et al.Normoxic ventilatory response in lowlander and Sherpa elite climbers[J].Respiration physiology,1998,113(1): 57-64.
[6]Shukitt-Hale B ,Banderet L E ,Lieberman H R .Relationships between symptoms,moods,performance,and acute mountain sickness at 4,700 meters[J].Aviation Space and Environmental Medicine,1991,62(9 Pt 1):865-869.
[7]BELHAGE B O,FRANDSEN A,SCHOUSBOE A.Temporal and spatial differences in intracellular Ca++ changes elicited by K+ and glutamate in single cultured neocortical neurons[J].Neurochemistry international,1996,29(3): 247-253.
[8]Shukitt-Hale B,Kadar T,Marlowe B E,et al.Morphological alterations in the hippocampus following hypobaric hypoxia[J].Human & experimental toxicology,1996,15(4): 312-319.
[9]Gozal D,Daniel J M,Dohanich G P.Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat[J].Journal of Neuroscience,2001,21(7):2442-2450.
[10]Sanchez R M,Koh S,Rio C,et al.Decreased glutamate receptor 2 expression and enhanced epileptogenesis in immature rat hippocampus after perinatal hypoxiainduced seizures[J].Journal of Neuroscience,2001,21(20): 8154-8163.
[11]Owens Jr J,Robbins C A,Wenzel H J,et al.Acute and chronic effects of hypoxia on the developing hippocampus[J].Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society,1997,41(2):187-199.
[12]Grojean S,Schroeder H,Pourié G,et al.Histopathological alterations and functional brain deficits after transient hypoxia in the newborn rat pup: a long term follow-up[J].Neurobiology of disease,2003,14(2): 265-278.
[13]Jensen F E,Holmes G L,Lombroso C T,et al.Age-dependent changes in long-term seizure susceptibility and behavior after hypoxia in rats[J].Epilepsia,1992,33(6): 971-980.
[14]Lai J C K,White B K,Buerstatte C R,et al.Chronic hypoxia in development selectively alters the activities of key enzymes of glucose oxidative metabolism in brain regions[J].Neurochemical research,2003,28(6): 933-940.
[15]Zola-Morgan S,Squire L R,Amaral D G.Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus[J].Journal of Neuroscience,1986,6(10): 2950-2967.
[16]Prigatano G P,Parsons O,Levin D C,et al.Neuropsychological test performance in mildly hypoxemic patients with chronic obstructive pulmonary disease[J].Journal of consulting and clinical psychology,1983,51(1): 108.
[17]Bédard M A,Montplaisir J,Richer F,et al.Obstructive sleep apnea syndrome:pathogenesis of neuropsychological deficits[J].Journal of clinical and experimental neuropsychology,1991,13(6): 950-964.(https://www.daowen.com)
[18]Viapiano M S,de Novara A M M,de Plazas S F,et al.Prolonged exposure to hypobaric hypoxia transiently reduces GABAA receptor number in mice cerebral cortex[J].Brain research,2001,894(1): 31-36.
[19]Pichiule P,Chávez J C,Boero J,et al.Chronic hypoxia induces modification of the N-methyl-D-aspartate receptor in rat brain[J].Neuroscience letters,1996,218(2):83-86.
[20]Reed L J,Marsden P,Lasserson D,et al.FDG-PET analysis and findings in amnesia resulting from hypoxia[J].Memory,1999,7(5-6): 599-614.
[21]Jänicke U A,Jänicke B,Schulze G,et al.Learning abilities of rats in multiple T-mazes of two degrees of complexity under the influence of d-amphetamine[J].Pharmacology Biochemistry and Behavior,1990,36(4): 923-932.
[22]Shukitt-Hale B,Stillman M J,Levy A,et al.Nimodipine prevents the in vivo decrease in hippocampal extracellular acetylcholine produced by hypobaric hypoxia[J].Brain research,1993,621(2): 291-295.
[23]Shukitt-Hale B,Kadar T,Marlowe B E,et al.Morphological alterations in the hippocampus following hypobaric hypoxia[J].Human & experimental toxicology,1996,15(4): 312-319.
[24]Gozal D,Daniel J M,Dohanich G P.Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat[J].Journal of Neuroscience,2001,21(7):2442-2450.
[25]Mohajeri M H,Saini K,Li H,et al.Intact spatial memory in mice with seizureinduced partial lossof hippocampal pyramidal neurons[J].Neurobiology of disease,2003,12(3): 174-181.
[26]Bitar F F,Bitar H,El Sabban M,et al.Modulation of ceramide content and lack of apoptosis in the chronically hypoxic neonatal rat heart[J].Pediatric research,2002,51(2): 144.
[27]Anooshiravani M,Dumont L,Mardirosoff C É,et al.Brain magnetic resonance imaging (MRI) and neurological changes after a single high altitude climb[J].Medicine and science in sports and exercise,1999,31(7): 969-972.
[28]Garrido E,Segura R,Capdevila A,et al.New evidence from magnetic resonance imaging of brain changes after climbs at extreme altitude[J].European journal of applied physiology and occupational physiology,1995,70(6): 477-481.
[29]Griggs R C,Sutton J R.Neurological manifestation of respiratory diseases[J].Disease of the Nervous System,1992: 1433-1439.
[30]Garrido E,Segura R,Capdevila A,et al.Are Himalayan Sherpas better protected against brain damage associated with extreme altitude climbs?[J].Clinical science,1996,90(1): 81-85.
[31]Hochachka P W,Clark C M,Matheson G O,et al.Effects on regional brain metabolism of high-altitude hypoxia: a study of six US marines[J].American Journal of Physiology-Regulatory,Integrative and Comparative Physiology,1999,277(1):R314-R319.
[32]Møller K,Paulson O B,Hornbein T F,et al.Unchanged cerebral blood flow and oxidative metabolism after acclimatization to high altitude[J].Journal of Cerebral Blood Flow & Metabolism,2002,22(1): 118-126.
[33]Hochachka P W,Buck L T,Doll C J,et al.Unifying theory of hypoxia tolerance:molecular/metabolic defense and rescue mechanisms for surviving oxygen lack[J].Proceedings of the national academy of sciences,1996,93(18): 9493-9498.
[34]Hochachka P W,Clark C M,Brown W D,et al.The brain at high altitude:hypometabolism as a defense against chronic hypoxia?[J].Journal of Cerebral Blood Flow & Metabolism,1994,14(4): 671-679.
[35]Hochachka P W,Clark C M,Matheson G O,et al.Effects on regional brain metabolism of high-altitude hypoxia: a study of six US marines[J].American Journal of Physiology-Regulatory,Integrative and Comparative Physiology,1999,277(1):R314-R319.
[36]Jansen G F A,Krins A,Basnyat B,et al.Cerebral autoregulation in subjects adapted and not adapted to high altitude[J].Stroke,2000,31(10): 2314-2318.
[37]Jansen G F,Krins A,Basnyat B,et al.Role of the altitude level on cerebral autoregulation in residents at high altitude[J].Journal of Applied Physiology,2007,103(2): 518-523.
[38]Yan X,Zhang J,Shi J,et al.Cerebral and functional adaptation with chronic hypoxia exposure: a multi-modal MRI study[J].Brain research,2010,1348: 21-29.