Hypoxic and ischemic hypoxia exacerbate brain injury associated with metabolic encephalopathy in laboratory animals.

Abstract

Hypoxemia is a major comorbid factor for permanent brain damage in several metabolic encephalopathies. To determine whether hypoxia impairs brain adaptation to hyponatremia, worsening brain edema, we performed in vitro and in vivo studies in cats and rats with hyponatremia plus either ischemic or hypoxic hypoxia. Mortality with hypoxic hypoxia was 0%; with hyponatremia, 22%; and with hyponatremia + hypoxia, 100%. Hyponatremia in cats produced brain edema, with a compensatory decrease of brain sodium. Ischemic hypoxia also resulted in brain edema, but with elevation of brain sodium. However, when ischemic hypoxia was superimposed upon hyponatremia, there was elevation of brain sodium with further elevation of water. Outward sodium transport in cat cerebral cortex synaptosomes was measured via three major pathways through which brain osmolality can be decreased. After hyponatremia, sodium transport was significantly altered such that brain cell osmolality would decrease: 44% increase in Na+-K+-ATPase transport activity (ouabain inhibitable); 26% decrease in amiloride-sensitive sodium uptake. The change in veratridine-stimulated sodium uptake was not significant (P > 0.05). When ischemic hypoxia was superimposed upon hyponatremia, all of the cerebral adaptive changes induced by hyponatremia alone were eliminated. Thus, hypoxia combined with hyponatremia produces a major increase in brain edema and mortality, probably by eliminating the compensatory mechanisms of sodium transport initiated by hyponatremia that tend to minimize brain swelling. (J. Clin. Invest. 1994.93:256-264.)

Clinical Semiology and Neuroradiologic Correlates of Acute Hypernatremic Osmotic Challenge in Adults: A Literature Review

“…The high hippocampal involvement may be related to its high vulnerability to the neurotoxic effects of osmotic derangements 49 and systemic stresses in general. 50,51 In reviewed cases, contrast enhancement associated with ODS lesions was reported in 1 patient, 23 which has also been reported in some cases of hyponatremia. 52 Although inconsistently found, contrast enhancement is in agreement with the pathophysiologic changes observed in experimental models of ODS, in which BBB disruption occurs secondary to osmotic stress and is thought to be one of the leading factors in pathogenesis of ODS.…”

Hyponatraemia

“…The authors also showed a failure of the adaptive mechanisms of the brain to chronic hyponatraemia in a number of the postmenopausal patients. This failure of cerebral adaptation may have been related to hypoxia, which has been shown in animal studies to impair the cerebral adaptive mechanisms to hyponatraemia (Vexler et al, 1994).…”

Pontine and extrapontine osmotic myelinolysis after the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report

“…It appears that ischemic hypoxia severely impairs the brain's adaptive mechanisms during hyponatremia by reducing cerebral oxygen availability. It may be an important comorbid factor in the morbidity associated with hyponatremic encephalopathy 22 . Bilateral basal ganglia lesions such as these may be seen in association with hypoxia, but in this case, no respiratory disturbance, cardiac arrest, or hypotension had occurred.…”