Combined clinical basic science seminar
Brain dysfunction in mild to moderate hypoxia

https://doi.org/10.1016/0002-9343(81)90834-2Get rights and content

Abstract

Hypoxia is commonly invoked to explain alterations in mental function, particularly in patients with cardiac or pulmonary failure. The effects of acute graded hypoxia on higher integrative functions are well documented experimentally in man. Hypoxia in experimental animal models demonstrates that the pathophysiology is complex. In mild to moderate hypoxia, in contrast to severe hypoxia and to ischemia, the supply of energy for the brain is not impaired; cerebral levels of adenosine triphosphate (ATP) and adenylate energy charge are normal. In contrast, the turnover of several neurotransmitters is altered by mild hypoxia. For example, acetylcholine synthesis is reduced proportionally to the reduction in carbohydrate oxidation. This relationship holds in vitro and with several in vivo models of hypoxia. Pharmacologic and physiologic studies in man and experimental animals are consistent with acetylcholine having an important role in mediating the cerebral effects of mild hypoxia. These observations raise the possibility that treatments directed to cholinergic or other central neurotransmitter systems may benefit patients with cerebral syndromes secondary to chronic hypoxia.

References (25)

  • HD Krop et al.

    Neuropsychological effects of continuous oxygen therapy in chronic obstructive pulmonary disease

    Chest

    (1973)
  • GE Gibson et al.

    Protection by THAM against behavioral and neurochemical effects of hypoxia

    Biochem Pharm

    (1979)
  • A Coronato et al.

    Lactic acidosis secondary to pernicious anemia

    Ann Intern Med

    (1969)
  • L Sokoloff

    Circulation and energy metabolism of the brain

  • U Luft

    Aviation physiology—the effects of altitude

  • B Siesjö et al.
  • A Otis et al.

    Performance as related to composition of alveolar air

    Am J Physiol

    (1946)
  • S Kety et al.

    The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men

    J Clin Invest

    (1948)
  • P Cohen et al.

    Effects of hypoxia and normocarbia on cerebral blood flow and metabolism in conscious man

    J Appl Physiol

    (1967)
  • S Shimojya et al.

    The effects of graded hypoxia upon transient, cerebral blood flow and oxygen consumption

    Neurology

    (1968)
  • ES Gurdjian et al.

    Cerebral metabolism in hypoxia

    Arch Neurol Psychiat

    (1944)
  • TE Duffy et al.

    Cerebral carbohydrate metabolism during acute hypoxia and recovery

    J Neurochem

    (1972)
  • Cited by (206)

    • Neurovascular coupling: motive unknown

      2022, Trends in Neurosciences
    • Abnormal brain oxygen homeostasis in an animal model of liver disease

      2022, JHEP Reports
      Citation Excerpt :

      In this study, we observe brain hypoperfusion at time points corresponding to previous reports of cognitive task performance impairment.10,29 We rely on the logical extension that a reduction in availability of metabolic substrates will lead to neuronal dysfunction manifesting neuropsychological impairment.51 Supporting the results of our study, Clément et al.50 recently demonstrated that in HE the brain, which is already compromised (decreased oxygenation and metabolic dysregulation), becomes susceptible to hypotensive insults resulting in neuronal cell death.

    View all citing articles on Scopus

    This study was supported by Grants NS 15649, NS 03346, NS 15125, NS 16994, AA03883 and the Winifred Masterson Burke Relief Foundation.

    1

    From the Department of Neurology, Cornell University Medical College, New York, New York, and the Dementia Research Program, Burke Rehabilitation Center, White Plains, New York.

    View full text