Elsevier

Brain Research

Volume 901, Issues 1–2, 18 May 2001, Pages 102-108
Brain Research

Research report
Effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation–reperfusion period after acute transient global hypoxia–ischemia in the newborn piglet

https://doi.org/10.1016/S0006-8993(01)02295-8Get rights and content

Abstract

This study was done to determine the effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation–reperfusion period after hypoxia–ischemia (HI). Forty-five newborn piglets were divided randomly into four experimental groups: normoxia control (NC, n=9); HI/reoxygenation–reperfusion (RR) control (HC, n=11); HI/RR hyperglycemia (HE, n=12); and HI/RR hypoglycemia (HO, n=13) group. Animals were subjected to transient HI for 30 min followed by 2 h of RR. Cerebral HI was induced by temporary but complete occlusion of bilateral common carotid arteries with surgical clips and simultaneous breathing with 8% oxygen. Glucose was unregulated in HC group, and controlled by modified glucose clamp technique immediately after HI in HE (350 mg/dl) and HO (50 mg/dl) groups. During HI, heart rate, base deficit, glucose and lactate level in the blood and cerebrospinal fluid increased, and arterial pH, oxygen saturation and blood pressure decreased significantly in HC, HE and HO groups. During RR, these abnormalities returned to normal values, but lactic acidosis persisted especially in HO group. Cerebral Na+,K+-ATPase activity decreased, and lipid peroxidation products increased significantly in HC group than in NC group, and these abnormalities were significantly aggravated in HE, but not in HO, group. Brain ATP and phosphocreatine levels in HE group were significantly reduced compared to the corresponding values in NC, HC and HO groups. In summary, hyperglycemia, but not hypoglycemia immediately after HI interfered with the recovery of brain cell membrane function and energy metabolism. These findings suggest that post-hypoxic–ischemic hyperglycemia is not beneficial and might even be harmful in neonatal hypoxic–ischemic encephalopathy.

Introduction

Perinatal hypoxic–ischemic brain injury remains a major cause of neonatal and infant mortality, and of permanent neurodevelopmental sequelae such as mental retardation, seizure disorders and cerebral palsy [25], [26]. Hyperglycemia or hypoglycemia is a frequent metabolic derangement among asphyxiated infants, and might have additive deleterious effects on the brain injury of perinatal asphyxia [3], [5], [13], [14], [23]. Thus, blood glucose concentration may be one of the variables affecting outcome of asphyxial insults. In our previous studies [3], [5], we demonstrated that neither hyperglycemia nor hypoglycemia was beneficial, and might even be harmful during hypoxic–ischemic brain injury in the newborn piglet. However, since it is practically impossible to institute some neuroprotective treatment during the primary asphyxial insult, it would be clinically more important to know the effects of blood glucose concentration after hypoxic–ischemic brain injury rather than during injury. Surprisingly, very few studies have been performed regarding the role of blood glucose concentration after hypoxic–ischemic brain damage in the neonatal animals, and the results are still contradictory [12], [13], [14], [15], [23]. Therefore, further studies will be necessary to clarify this.

This study was done to determine whether alterations in posthypoxic–ishcemic blood glucose concentrations could affect the severity of cerebral injury in the developing brain. We tested the hypothesis that hyperglycemia or hypoglycemia during the immediate reoxygenation-reperfusion period after acute transient global hypoxia–ishcemia interferes with recovery in brain cell membrane function and energy metabolism in the newborn piglet. We used the same hypoxic–ischemic model of newborn piglets previously described [3], [4], [5]. Hyperglycemia (blood glucose level 350 mg/dl) or hypoglycemia (blood glucose level 50 mg/dl) was instituted and maintained by modified glucose clamp technique with glucose or insulin infusion, respectively [3], [5], [19]. Changes in brain cell membrane structure, function and energy metabolism were determined by measuring lipid peroxidation products (conjugated dienes), Na+,K+-ATPase activity and concentrations of cerebral high-energy phosphate compounds in the cerebral cortex.

Section snippets

Animal preparation

The experimental protocols described herein were reviewed and approved by the Institutional Animal Care and Use Committee of the Samsung Biomedical Research Center, Seoul, South Korea. This study also followed the institutional and National Institutes of Health guidelines for laboratory animal care.

Newborn piglets less than 3 days old and of mixed strain (Yorkshire, conventional breed, purchased from Paju farm, Paju, Kyonggi-Do, Korea) were used in this study. Animals inhaled ether for

Physiologic variables

The mean physiologic variables from the four experimental groups were summarized in Table 1. In NC group, there were no significant changes in the values of physiologic variables including heart rate, arterial blood gases and mean arterial blood pressure during the experiment. During hypoxia–ischemia, heart rate increased, and mean arterial blood pressure, arterial oxygen tension, base excess and pH decreased significantly in HC, HE and HO groups compared to the corresponding values in NC

Discussion

In this study, we investigated the role of blood glucose concentration after hypoxic–ischemic insult in the developing newborn brain. Our data demonstrated potentially detrimental effects of hyperglycemia, but not hypoglycemia, during the immediate reoxygenation–reperfusion period after acute transient global hypoxia–ischemia in the newborn piglet. Hyperglycemia hampered the recovery in brain ATP and phosphocreatine levels, and aggravated brain damage as indicated by reduced cerebral cortical

Acknowledgements

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (HMP-00-B-21300-0204).

References (26)

  • D.W. Choi

    Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage

    Trends Neurosci.

    (1988)
  • H.T. Chugani et al.

    Positron emission tomography study of human brain functional development

    Ann. Neurol.

    (1987)
  • R. Corbett et al.

    Age-related differences in the effect of dichloroacetate on postischemic lactate and acid clearance measured in vivo using magnetic resonance spectroscopy and microdialysis

    J. Neurochem.

    (1998)
  • Cited by (0)

    View full text