Cerebral Energy Metabolism Studied With Phosphorus NMR Spectroscopy in Normal and Birth-Asphyxiated Infants

Hope, Peter

doi:10.1016/s0140-6736(84)90539-7

Cited by 299 publications

(120 citation statements)

References 17 publications

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“…The estimate of the intracellular 425 P. TOFTS AND S. WRA Y pH of the brain did not vary with age. The mean value found, 7-21 +0-02, is similar to the value found in human neonates, 7-14+010 (Hope et al 1984). It should be noted, however, that pH values depend upon the calibration curve used and that the apparent resonance position of a peak can be influenced by large, overlapping neighbouring peaks.…”

Section: Discussionsupporting

confidence: 78%

“…Recently, the brains of new-born infants have been examined (Cady, Costello, Dawson, Delpy, Hope, Reynolds, Tofts& Wilkie, 1983 babies, low ratios of PCr/P1 (<08), were found to be associated with a very bad prognosis for survival and early neurodevelopmental outcome (Hope, Costello, Cady, Delpy, Tofts, Chu, Hamilton, Reynolds & Wilkie, 1984). The spectra from human infant brains differed from those found previously for animal brains (e.g.…”

Section: Introductionmentioning

confidence: 90%

“…The identity of the PME peak is not yet known with absolute certainty. Earlier suggestions that it was ribose-5-phosphate (Glonek, Kopp, Kot, Pettegrew, Harrison & Cohen, 1982) are now not thought to be correct (see Hope et al 1984). Examination of rat brain extracts by gas chromatography and n.m.r.…”

Section: Possible Functional Significance Of the Developmental Changesmentioning

confidence: 99%

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Changes in brain phosphorus metabolites during the post‐natal development of the rat.

Tofts¹,

Wray²

1985

The Journal of Physiology

100

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SUMMARY1. Changes in brain phosphorus metabolites during the post-natal development of the rat and in neonatal and adult guinea-pigs have been studied in vivo using 31P nuclear magnetic resonance spectroscopy (n.m.r.s.).2. The brain spectra showed clear differences with age, particularly during the first 3 weeks post-partum.3. The spectra from 4-day-old rats resembled those of new-born human infants. We suggest that the differences between human and animal brains seen in previously published spectra arise because of an age difference rather than a species difference.4. The phosphocreatine (PCr) to nucleoside triphosphate (NTP) ratio increased from around 1-0 in 3-day-old rats to 1P8 in adult animals. The adult ratio is larger than that previously reported from in vitro chemical analyses.5. An unknown compound in the phosphomonoester (PME) region of the spectra predominated in young animals, but decreased in concentration relative to NTP with age and reached adult values by around 2 weeks post-partum.6. Neonatal guinea-pigs, which are much more developed at birth than the rat, had a significantly greater PCr/NTP ratio than the neonatal rat, but their brain spectra also contained the large PME peak.7. The intracellular pH of cerebral tissue was estimated to be 7-21 +0-02 and did not show any change with age.8. The changes we find in the phosphorus compounds in the brain may be of importance in post-natal development, and the possible functional significance of these results is discussed.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 90%

Section: Possible Functional Significance Of the Developmental Changesmentioning

confidence: 99%

See 1 more Smart Citation

Changes in brain phosphorus metabolites during the post‐natal development of the rat.

Tofts¹,

Wray²

1985

The Journal of Physiology

100

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“…Recent studies in premature and full term newborns using 31p NMR spectroscopy have demonstrated that hypoxia-ischemia is associated with lingering alterations in the energy state of the brain occurring as a consequence of tissue injury (Hope et al, 1984;Younkin et al, 1984;Hamilton et al, 1986). Persistent biochemical abnormalities include relative decreases in the spectra of P-Cr and ATP with concurrent increases in inorganic phosphate (PJ, leading to reductions in the P�Cr/Pi and ATP/Pi ratios.…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate and Energy Metabolism during the Evolution of Hypoxic-Ischemic Brain Damage in the Immature Rat

Palmer

Brucklacher

Christensen

et al. 1990

J Cereb Blood Flow Metab

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Summary: The brain damage that evolves from perinatal cerebral hypoxia-ischemia may involve lingering distur bances in metabolic activity that proceed into the recov ery period. To clarify this issue, we determined the car bohydrate and energy status of cerebral tissue using en zymatic, fluorometric techniques in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-day postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37°C. This insult is known to produce tissue injury (selective neuronal necrosis or infarction) predominantly in the cerebral hemisphere ipsilateral to the carotid artery occlusion in 92% of the animals. Rat pups were quick-frozen in liquid nitrogen at 0, 1, 4, 12, 24, or 72 h of recovery; littermate controls underwent neither ligation nor hypoxia. Glucose in both cerebral hemi spheres was nearly completely exhausted during hypoxia ischemia, with concurrent increases in lactate to 10 mmoU kg. During recovery, glucose promptly increased above control values, suggesting an inhibition of glycolytic flux, as documented in the ipsilateral cerebral hemisphere by measurement of glucose utilization (CMRg1c) at 24 h. Tis sue lactate declined rapidly during recovery but remained slightly elevated in the ipsilateral hemisphere for 12 h.Cerebral hypoxia-ischemia is a frequent accom paniment to high-risk pregnancy and labor, and oc casionally culminates in brain damage with its as sociated neurologic impairment (F enichel, 1983;Volpe, 1987;Vannucci, 1989). The pathophysio- Abbreviations used: 2-DG, 2-deoxyglucose; MCA, middle ce rebral artery; NMR, nuclear magnetic resonance; PCA, perchlo ric acid; P-Cr, phosphocreatine. 227Phosphocreatine (P-Cr) and ATP in the ipsilateral cere bral hemisphere were 14 and 26% of control (p < 0.001) at the end of hypoxia-ischemia; total adenine nUcleotides (A TP + ADP + AMP) also were partially depleted (-46%). During the first hour of recovery, mean P-Cr was replenished to within 90% of baseline, whereas mean ATP was incompletely restored to 68-81 % of control (p < 0.05). Individual ATP and total adenine nucleotide values were >2 SD below control levels in 17/24 (71%) brains at all intervals of recovery. Both ATP and total adenine nu cleotides were inversely correlated with tissue water con tent, reflecting the extent of cerebral edema. No major alterations in the high-energy phosphate reserves oc curred in the contralateral cerebral hemisphere either during or following hypoxia-ischemia. Thus, following perinatal cerebral hypoxia-ischemia, ATP and total ade nine nUcleotides never recover completely in brains un dergoing damage but rather are permanently depleted to levels that reflect the severity of tissue injury. Recovery of P-Cr to near normal levels can occur despite evolving brain damage. The findings have relevance to the assess ment of asphyxiated newborn humans using magnetic res onance spectroscopy.

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“…Luego de esta, el metabolismo puede deteriorarse nuevamente (fase de fracaso energético secundario). 17,18 Es en esta última fase cuando se produce la muerte por necrosis y por apoptosis de los elementos celulares neurales.…”

Section: Fisiopatología De La Asfixiaunclassified

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Cerebral Energy Metabolism Studied With Phosphorus NMR Spectroscopy in Normal and Birth-Asphyxiated Infants

Cited by 299 publications

References 17 publications

Changes in brain phosphorus metabolites during the post‐natal development of the rat.

Changes in brain phosphorus metabolites during the post‐natal development of the rat.

Carbohydrate and Energy Metabolism during the Evolution of Hypoxic-Ischemic Brain Damage in the Immature Rat

Recomendación para el tratamiento con hipotermia en recién nacidos con encefalopatía hipóxico- isquémica

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