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Hypothermia therapy for neonatal encephalopathy

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Hypothermia therapy for neonatal encephalopathy
Specialtyneonatologist(pediatrician)

Mild total body hypothermia, induced by cooling a baby to 33-34°C for three days after birth, is nowadays a standardized treatment after moderate to severe hypoxic ischemic encephalopathy in full-term and near to fullterm neonates.[1][2] It has recently been proven to be the only medical intervention which reduces brain damage, and improves an infant's chance of survival and reduced disability.

Hypoxic ischemic encephalopathy has many causes and is defined essentially as the reduction in the supply of blood or oxygen to a baby's brain before, during, or even after birth. It is a major cause of death and disability, occurring in approximately 2–3 per 1000 births and causing around 20% of all cases of cerebral palsy. A 2013 Cochrane review found that therapeutic hypothermia is useful in full term babies with encephalopathy.[3]

Medical uses

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Extended follow-up of trial participants

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Studies have been undertaken to determine the effects of hypothermia beyond early childhood. Participants in the CoolCap, NICHD and TOBY trials were entered into extended follow-up programmes. None of these programmes have sufficient power to make confident assessments of the long-term effect of hypothermia, however even these underpowered studies give important information on whether the therapeutic effects of cooling are sustained beyond the first two years after birth.

The most significant follow-up study published so far is the assessment of the NICHD trial participants at 6–7 years.[4] Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). The CoolCap study gathered data using the WeeFim questionnaire at 7–8 years of age, but only collected information on 62 (32 cooled; 30 standard care) of 135 surviving children who had had neurodevelopmental assessment at 18 months. Disability status at 18 months was strongly associated with WeeFIM ratings (P < 0.001) suggesting that the therapeutic effect persisted, but there was no significant effect of treatment (P = 0.83).[5]

These results were not quite conclusive, as the effect in the NICHD trial appears to be on mortality rather than neurological function, but they gave considerable confidence that the therapeutic effects of hypothermia following birth asphyxia are sustained into later childhood, and when the Toby trial childhood follow up was published in the New England Journal of Medicine it confirmed the persistence of the effect [6]

Current state of the evidence

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Hypothermic neural rescue therapy is an evidence-based clinical treatment which increases a severely injured full term infant's chance of surviving without brain damage detectable at 18 months by about 50%, an effect which seems to be sustained into later childhood.

At present data relate only to full term infants, and all human studies of hypothermia treatment have so far been restricted to infants >36 weeks out of an expected 40 weeks gestation. There are both more potential side effects on the developing premature with lung disease, and there is more evident protection by hypothermia when a greater volume of complex brain is actively developing. During mid gestation to late term the fetal brain is undergoing increasingly complex progressive growth of first the mid-brain and then development of the cortex and "higher" centers. The effects of fetal asphyxia on the developing brain in sheep are dependent on gestational age with near term fetuses showing both less tolerance of asphyxia and maximal damage in the rapidly expanding cortex; while fetuses prior to the last third of development experience more extended tolerance of asphyxia with maximal effects on the growing mid-brain. The fetal sheep asphyxia model also suggests a six-hour window post asphyxia in which hypothermia will have greatest benefit.

Since the prerequisites regarding immediate closeness after giving birth radically chances, researchers have become curious regarding parent's experiences and how to improve the nursing care around effects families. In interviews made by different researchers in different countries it has been clear the parents want clear communication with the NICU staff, but also in between the NICU staff and the obstetrics staff.[7] They also described a strong wish touching and being really close to their baby but also actively participate in the baby's care [8]

There remains much that is unknown. Recognition of infants with marginal external signs of asphyctic damage at birth, who still develop moderate hypoxic ischemic encephalopathy would be enhanced by finding more reliable bio-markers or physiologic tests accurately predicting the risk for progressive damage. These tests could also prevent unwarranted, expensive treatment of many infants. Long-term follow-up has yet to demonstrate show persisting benefit, but available data together with an imaging study nested in TOBY also found reduced brain tissue damage in cooled infants are encouraging.[9]

The simplicity that attracted empiricists to cooling centuries ago now makes hypothermic neural rescue with accurate patient selection a potentially transforming therapy for low-resource environments where birth asphyxia remains a major cause of death and disability. Ironically this brings back the problem of cooling infants in an environment where modern resuscitation and intensive care are not available.[10]

Mechanisms of action

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Much of what is known about the mechanisms of hypothermic neuroprotection is gathered from studies in mature and adult models. What follows uses some of these data while trying to focus on the immature brain.

Hypoxia-ischaemia

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Cerebral hypoxia-ischaemia results in reduced cerebral oxidative metabolism, cerebral lactic acidosis and cell membrane ionic transport failure; if prolonged there is necrotic cell death.[11][12] Although rapid recovery of cerebral energy metabolism occurs following successful resuscitation this is followed some hours later by a secondary fall in cerebral high energy phosphates accompanied by a rise in intracellular pH, and the characteristic cerebral biochemical disturbance at this stage is a lactic alkalosis.[13] In neonates, the severity of this secondary impairment in cerebral metabolism are associated with abnormal subsequent neurodevelopmental outcome and reduced head growth.[14][15]

Several adverse biological events contribute to this secondary deterioration, including: release of excitatory amino acids which activate N-methyl-D-aspartate (NMDA) and amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors on neurons (30,37) and oligodendroglial precursors, accumulation of excitatory neurotransmitters, generation of reactive oxygen radicals, intracellular calcium accumulation and mitochondrial dysfunction.[16] Whilst necrotic cell death is prominent in the immediate and acute phases of severe cerebral insults, the predominant mode of death during the delayed phase of injury appears to be apoptosis.[17] Neuroprotective mechanisms need to interact with these mechanisms to have beneficial effect.

Newborn hypoxic-ischaemic brain injury differs from injury in the adult brain in several ways: NMDA receptor toxicity is much higher in the immature brain.[18] Apoptotic mechanisms including activation of caspases, translocation of apoptosis-inducing factor and cytochrome-c release are much greater in the immature than the adult.[19][20][21] The inflammatory activation is different with less contribution from polymorphonuclear cells[22] and a more prominent role of IL-18[23] whereas IL-1, which is critical in the adult brain,[24] is less important.[25] The anti-oxidant system is underdeveloped with reduced capacity to inactivate hydrogen peroxide.[26]

Actions of hypothermia

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Mild hypothermia helps prevent disruptions to cerebral metabolism both during and following cerebral insults. Hypothermia decreases the cerebral metabolic rate for glucose and oxygen and reduces the loss of high energy phosphates during hypoxia-ischaemia[27] and during secondary cerebral energy failure,[28] and reduces delayed cerebral lactic alkalosis.[29] The simultaneous increase in cytotoxic oedema and loss of cerebral cortical activity that accompanies secondary energy failure is also prevented.[30]

Hypothermia appears to have multiple effects at a cellular level following cerebral injury. Hypothermia reduces vasogenic oedema, haemorrhage and neutrophil infiltration after trauma.[31] The release of excitatory neurotransmitters is reduced, limiting intracellular calcium accumulation.[32][33][34] Free radical production is lessened, which protects cells and cellular organelles from oxidative damage during reperfusion.[35] In addition mild hypothermia may reduce the activation of the cytokine and coagulation cascades through increased activation of suppressor signalling pathways, and by inhibiting release of platelet activating factor.[36]

Many of the effects induced by mild hypothermia may help to reduce the number of cells undergoing apoptosis. Experimental and clinical studies indicate that the number of apoptotic neurons is reduced caspase activity is lessened and cytochrome c translocation is diminished by mild hypothermia,[37][38] and there may be an increase in expression of the anti-apoptotic protein BCl-2.[39]

History

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Many physicians over the centuries have tried to resuscitate babies after birth by altering their body temperatures, essentially aiming to animate the infant by inducing the onset of breathing.[40] Little thought was given to brain protection, because cerebral hypoxia during birth was not linked with later neurological problems until William John Little in 1861,[41] and even then this was controversial; Sigmund Freud, for example, famously disagreed, and when scientific studies of neonatal therapeutic hypothermia were begun in the 1950s researchers like Bjorn Westin still reported their work in terms of re-animation rather than neuroprotection.[42] Investigators such as James Miller and Clement Smith carried out clinical observations and careful physiological experiments,[43][44][45][46] but although some babies were conscientiously followed up, they were not mainly concerned with long term neurological outcome.

However, by the 1960s physicians saw hypothermia after delivery as something to be avoided. The problem of infants who failed to breathe at birth had been solved by the invention of mechanical ventilation, so any benefit cooling might have for re-animation was no longer needed, and an influential trial showed that keeping small and preterm infants warm increased survival.[47] These results, together with observational[48] and experimental[49] data made it an article of medical faith for decades that babies should not be allowed to get cold.

Consequently, during the next two decades studies of neonatal hypothermia in Europe and the USA were sporadic and often unsuccessful. An interest in cooling for brain protection was beginning to emerge, but contemporary neuroscience provided few useful concepts to guide this research and little progress was made.[50][51][52][53][54][55][56] Although across the Iron Curtain in the Soviet Union cooling was being applied empirically following birth asphyxia,[57] the language barrier, cold war politics and the Russians' failure to carry out randomised controlled trials contributed to an almost total ignorance of this work in the West. Indeed, a group of Russian neonatologists who described hypothermic neural rescue during a visit to the Neonatal Unit in Bristol, UK, met with little interest.[58]

Neural rescue

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In the late 1980s the development of a new set of concepts and problems led to a re-examination. A new generation of neonatal researchers were influenced by the growing evidence that protecting the brain against the effects of oxygen deprivation during labour might be possible. These researchers were aware that cooling produced powerful intra-ischaemic neuroprotection during cardiac surgery but a new concept of hypothermic post-insult neural rescue developed. This shift in thinking was possible because of at least three major new ideas that were developing at the same time: delayed post-ischaemic cell death; excitotoxicity; and apoptosis.

Delayed cell death

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The first paradigm shift that affected neonatal researchers in particular was the idea that if a baby was resuscitated after cerebral hypoxia-ischaemia there was a period of time before brain cells started to die. Osmund Reynolds at University College London used the newly developed technique of Magnetic Resonance Spectroscopy (MRS) to show that the infant brain metabolism is normal in the hours after birth asphyxia and deteriorated only after a distinct delay.[59] Robert Vannucci confirmed the effect with painstaking biochemistry,[60] and delayed injury was also reported in neuropathological studies.[61][62]

Delayed brain injury (called 'secondary energy failure' by Reynolds) was a critical new idea. If brain cells remained normal for a time and the mechanism of the delayed death could be unravelled, it opened the possibility of therapeutic intervention in what had previously seemed an impossible situation.[63]

Excitotoxicity

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The new and transforming concept of excitotoxicity developed from the seminal experiments of John Olney[64][65] and Brian Meldrum.[66] They showed that at least some of the neural cell death caused by hypoxia-ischaemia is mediated by excess production of the excitatory neurotransmitter glutamate, and that pharmacological blockade of the N-methyl-D-aspartate receptor could provide good protection against hypoxic damage. Olney and Meldrum had shifted the paradigm, allowing researchers to think of hypoxic-ischaemic damage as a treatable disease.

Apoptosis

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However, it was still a mystery how and why cells triggered by hypoxia-ischaemia should die hours or days later, particularly when it became clear that glutamate levels were not particularly high during secondary energy failure. The next critical idea came with the discovery of programmed cell death, a novel form of cell suicide. Originally observed as a pathological appearance and named apoptosis ("falling off", as of leaves) in the 1970s,[67] Horvitz,[68] Raff[69] and Evan[70] provided a molecular understanding and showed that apoptosis could be triggered by cellular insults. The radical idea that hypoxia-ischaemia triggered a cell suicide programme which could explain the perplexing phenomenon of delayed cell death was soon supported by experimental[71][72] and human data,[73] and many researchers believe this helps explain why neural rescue works in the newborn. However the picture is complex: both apoptosis and necrosis are present in variable proportions;[74] and there seems to be prolonged neurodegeneration after an insult.[75] Research into this problem continues.

Neonatal neural rescue

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These ideas flowed through the perinatal research community, producing a new belief that neural rescue after birth asphyxia should be possible. Amongst the first to have attempt neonatal neural rescue in animals were Ingmar Kjellmer and Henrik Hagberg in Gothenburg,[76][77] and Michael Johnston in Baltimore.[78] The potential began to draw in other neonatal researchers from diverse fields to begin neuroprotection research, including those who came to form the informal neonatal hypothermia research group:

Peter Gluckman and Tania Gunn were endocrinologists in the University of Auckland New Zealand and interested in cooling for its effect on thyroid function; they had first cooled a sheep fetus for endocrine studies in 1983. Denis Azzopardi, John Wyatt and David Edwards, then young researchers working for Reynolds, were using Reynolds's sophisticated MRS approach to replicate secondary energy failure in newborn piglets[28] and immature rats;[79] in Gluckman's laboratory Alistair Gunn and Chris Williams developed a simple and elegant biophysical method using cerebral impedance to do essentially the same thing in fetal sheep.[80] Marianne Thoresen, who was working on cerebral perfusion, was prompted to think about neuroprotection by stories of children who fell through the Norwegian ice and suffering prolonged drowning in iced water but emerged with preserved cerebral function.

There were many potential therapies around which might achieve neural rescue, and most of these workers did not immediately move to hypothermia. Magnesium was an appealingly simple excitoxin receptor antagonist that protected cells in culture: the Reynolds group tested it in their piglet model without success.[81] Gluckman and Gunn started by looking unsuccessfully at flunarizine, a calcium entry inhibitor.[82] Edwards picked on nitric oxide synthase inhibition which was also a failure.[83] Gluckman had success with his innovative studies of IGF-1, but could not immediately translate this to clinical practice.[84]

References

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  1. ^ Azzopardi D, Brocklehurst P, Edwards D, Halliday H, Levene M, Thoresen M, Whitelaw A (April 2008). "The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial". BMC Pediatrics. 8 (1): 17. doi:10.1186/1471-2431-8-17. PMC 2409316. PMID 18447921.
  2. ^ Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. (October 2005). "Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy". The New England Journal of Medicine. 353 (15): 1574–1584. doi:10.1056/nejmcps050929. PMID 16221780.
  3. ^ Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG (January 2013). "Cooling for newborns with hypoxic ischaemic encephalopathy". The Cochrane Database of Systematic Reviews. 1 (1): CD003311. doi:10.1002/14651858.CD003311.pub3. PMC 7003568. PMID 23440789.
  4. ^ Shankaran S, Pappas A, McDonald SA, Vohr BR, Hintz SR, Yolton K, et al. (Eunice Kennedy Shriver NICHD Neonatal Research Network) (May 2012). "Childhood outcomes after hypothermia for neonatal encephalopathy". The New England Journal of Medicine. 366 (22): 2085–2092. doi:10.1056/NEJMoa1112066. PMC 3459579. PMID 22646631.
  5. ^ Guillet R, Edwards AD, Thoresen M, Ferriero DM, Gluckman PD, Whitelaw A, Gunn AJ (February 2012). "Seven- to eight-year follow-up of the CoolCap trial of head cooling for neonatal encephalopathy". Pediatric Research. 71 (2): 205–209. doi:10.1038/pr.2011.30. PMID 22258133.
  6. ^ Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, Goodwin J, Halliday HL, Juszczak E, Kapellou O, Levene M, Linsell L, Omar O, Thoresen M, Tusor N, Whitelaw A, Edwards AD; TOBY Study Group. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med. 2014 Jul 10;371(2):140-9. doi: 10.1056/NEJMoa1315788. PMID 25006720.
  7. ^ Craig AK, Gerwin R, Bainter J, Evans S, James C (July 2018). "Exploring parent expectations of neonatal therapeutic hypothermia". Journal of Perinatology. 38 (7): 857–864. doi:10.1038/s41372-018-0117-8. PMC 6486821. PMID 29740186.
  8. ^ Bäcke P, Hjelte B, Hellström Westas L, Ågren J, Thernström Blomqvist Y (February 2021). "When all I wanted was to hold my baby-The experiences of parents of infants who received therapeutic hypothermia". Acta Paediatrica. 110 (2): 480–486. doi:10.1111/apa.15431. PMID 32564441. S2CID 219974541.
  9. ^ Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, et al. (January 2010). "Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial". The Lancet. Neurology. 9 (1): 39–45. doi:10.1016/S1474-4422(09)70295-9. PMC 2795146. PMID 19896902.
  10. ^ Robertson NJ, Nakakeeto M, Hagmann C, Cowan FM, Acolet D, Iwata O, et al. (September 2008). "Therapeutic hypothermia for birth asphyxia in low-resource settings: a pilot randomised controlled trial". Lancet. 372 (9641): 801–803. doi:10.1016/S0140-6736(08)61329-X. PMID 18774411. S2CID 5604408.
  11. ^ Siesjö BK, Katsura K, Kristián T (January 1995). "The biochemical basis of cerebral ischemic damage". Journal of Neurosurgical Anesthesiology. 7 (1): 47–52. doi:10.1097/00008506-199501000-00009. PMID 7881240. S2CID 30811605.
  12. ^ Siesjö BK (1981). "Cell damage in the brain: a speculative synthesis". Journal of Cerebral Blood Flow and Metabolism. 1 (2): 155–185. doi:10.1038/jcbfm.1981.18. PMID 6276420.
  13. ^ Taylor DL, Edwards AD, Mehmet H (January 1999). "Oxidative metabolism, apoptosis and perinatal brain injury". Brain Pathology. 9 (1): 93–117. doi:10.1111/j.1750-3639.1999.tb00213.x. PMC 8098214. PMID 9989454. S2CID 28853873.
  14. ^ Roth SC, Edwards AD, Cady EB, Delpy DT, Wyatt JS, Azzopardi D, et al. (April 1992). "Relation between cerebral oxidative metabolism following birth asphyxia, and neurodevelopmental outcome and brain growth at one year". Developmental Medicine and Child Neurology. 34 (4): 285–295. doi:10.1111/j.1469-8749.1992.tb11432.x. PMID 1572514. S2CID 6823414.
  15. ^ Robertson NJ, Cox IJ, Cowan FM, Counsell SJ, Azzopardi D, Edwards AD (September 1999). "Cerebral intracellular lactic alkalosis persisting months after neonatal encephalopathy measured by magnetic resonance spectroscopy". Pediatric Research. 46 (3): 287–296. doi:10.1203/00006450-199909000-00007. PMID 10473043.
  16. ^ Siesjö BK, Elmér E, Janelidze S, Keep M, Kristián T, Ouyang YB, Uchino H (1999). "Role and Mechanisms of Secondary Mitochondrial Failure". Current Progress in the Understanding of Secondary Brain Damage from Trauma and Ischemia. Vol. 73. pp. 7–13. doi:10.1007/978-3-7091-6391-7_2. ISBN 978-3-7091-7312-1. PMID 10494335. {{cite book}}: |journal= ignored (help)
  17. ^ Northington FJ, Ferriero DM, Graham EM, Traystman RJ, Martin LJ (April 2001). "Early Neurodegeneration after Hypoxia-Ischemia in Neonatal Rat Is Necrosis while Delayed Neuronal Death Is Apoptosis". Neurobiology of Disease. 8 (2): 207–219. doi:10.1006/nbdi.2000.0371. PMID 11300718. S2CID 22151962.
  18. ^ McDonald JW, Johnston MV (1990). "Physiological and pathophysiological roles of excitatory amino acids during central nervous system development". Brain Research. Brain Research Reviews. 15 (1): 41–70. doi:10.1016/0165-0173(90)90011-C. hdl:2027.42/28778. PMID 2163714. S2CID 16878464.
  19. ^ Wang X, Carlsson Y, Basso E, Zhu C, Rousset CI, Rasola A, et al. (February 2009). "Developmental shift of cyclophilin D contribution to hypoxic-ischemic brain injury". The Journal of Neuroscience. 29 (8): 2588–2596. doi:10.1523/JNEUROSCI.5832-08.2009. PMC 3049447. PMID 19244535.
  20. ^ Northington FJ, Ferriero DM, Flock DL, Martin LJ (March 2001). "Delayed neurodegeneration in neonatal rat thalamus after hypoxia-ischemia is apoptosis". The Journal of Neuroscience. 21 (6): 1931–1938. doi:10.1523/JNEUROSCI.21-06-01931.2001. PMC 6762598. PMID 11245678.
  21. ^ Gill R, Soriano M, Blomgren K, Hagberg H, Wybrecht R, Miss MT, et al. (April 2002). "Role of caspase-3 activation in cerebral ischemia-induced neurodegeneration in adult and neonatal brain". Journal of Cerebral Blood Flow and Metabolism. 22 (4): 420–430. doi:10.1097/00004647-200204000-00006. PMID 11919513.
  22. ^ Bona E, Andersson AL, Blomgren K, Gilland E, Puka-Sundvall M, Gustafson K, Hagberg H (April 1999). "Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats". Pediatric Research. 45 (4 Pt 1): 500–509. doi:10.1203/00006450-199904010-00008. PMID 10203141.
  23. ^ Hedtjärn M, Leverin AL, Eriksson K, Blomgren K, Mallard C, Hagberg H (July 2002). "Interleukin-18 involvement in hypoxic-ischemic brain injury". The Journal of Neuroscience. 22 (14): 5910–5919. doi:10.1523/JNEUROSCI.22-14-05910.2002. PMC 6757918. PMID 12122053.
  24. ^ Boutin H, LeFeuvre RA, Horai R, Asano M, Iwakura Y, Rothwell NJ (August 2001). "Role of IL-1alpha and IL-1beta in ischemic brain damage". The Journal of Neuroscience. 21 (15): 5528–5534. doi:10.1523/JNEUROSCI.21-15-05528.2001. PMC 6762680. PMID 11466424.
  25. ^ Hedtjärn M, Mallard C, Iwakura Y, Hagberg H (2005). "Combined deficiency of IL-1beta18, but not IL-1alphabeta, reduces susceptibility to hypoxia-ischemia in the immature brain". Developmental Neuroscience. 27 (2–4): 143–148. doi:10.1159/000085986. PMID 16046848. S2CID 85288351.
  26. ^ Ferriero DM (November 2004). "Neonatal brain injury". The New England Journal of Medicine. 351 (19): 1985–1995. doi:10.1056/NEJMra041996. PMID 15525724.
  27. ^ Erecinska M, Thoresen M, Silver IA (May 2003). "Effects of hypothermia on energy metabolism in Mammalian central nervous system". Journal of Cerebral Blood Flow and Metabolism. 23 (5): 513–530. doi:10.1097/01.WCB.0000066287.21705.21. PMID 12771566.
  28. ^ a b Lorek A, Takei Y, Cady EB, Wyatt JS, Penrice J, Edwards AD, et al. (December 1994). "Delayed ("secondary") cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy". Pediatric Research. 36 (6): 699–706. doi:10.1203/00006450-199412000-00003. PMID 7898977.
  29. ^ Amess PN, Penrice J, Cady EB, Lorek A, Wylezinska M, Cooper CE, et al. (June 1997). "Mild hypothermia after severe transient hypoxia-ischemia reduces the delayed rise in cerebral lactate in the newborn piglet". Pediatric Research. 41 (6): 803–808. doi:10.1203/00006450-199706000-00002. PMID 9167192. S2CID 35788986.
  30. ^ Gunn AJ, Gunn TR, Gunning MI, Williams CE, Gluckman PD (November 1998). "Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep". Pediatrics. 102 (5): 1098–1106. doi:10.1542/peds.102.5.1098. PMID 9794940. S2CID 45463848.
  31. ^ Smith SL, Hall ED (January 1996). "Mild pre- and posttraumatic hypothermia attenuates blood-brain barrier damage following controlled cortical impact injury in the rat". Journal of Neurotrauma. 13 (1): 1–9. doi:10.1089/neu.1996.13.1. PMID 8714857.
  32. ^ Busto R, Globus MY, Dietrich WD, Martinez E, Valdés I, Ginsberg MD (July 1989). "Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain". Stroke. 20 (7): 904–910. doi:10.1161/01.str.20.7.904. PMID 2568705.
  33. ^ Thoresen M, Satas S, Puka-Sundvall M, Whitelaw A, Hallström A, Løberg EM, et al. (October 1997). "Post-hypoxic hypothermia reduces cerebrocortical release of NO and excitotoxins". NeuroReport. 8 (15): 3359–3362. doi:10.1097/00001756-199710200-00033. PMID 9351672. S2CID 24761799.
  34. ^ Nakashima K, Todd MM (May 1996). "Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization". Stroke. 27 (5): 913–918. doi:10.1161/01.str.27.5.913. PMID 8623113.
  35. ^ Globus MY, Alonso O, Dietrich WD, Busto R, Ginsberg MD (October 1995). "Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia". Journal of Neurochemistry. 65 (4): 1704–1711. doi:10.1046/j.1471-4159.1995.65041704.x. PMID 7561868. S2CID 35183612.
  36. ^ Akisu M, Huseyinov A, Yalaz M, Cetin H, Kultursay N (July 2003). "Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 69 (1): 45–50. doi:10.1016/S0952-3278(03)00055-3. PMID 12878450.
  37. ^ Edwards AD, Yue X, Squier MV, Thoresen M, Cady EB, Penrice J, et al. (December 1995). "Specific inhibition of apoptosis after cerebral hypoxia-ischaemia by moderate post-insult hypothermia". Biochemical and Biophysical Research Communications. 217 (3): 1193–1199. doi:10.1006/bbrc.1995.2895. PMID 8554576.
  38. ^ Xu L, Yenari MA, Steinberg GK, Giffard RG (January 2002). "Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade". Journal of Cerebral Blood Flow and Metabolism. 22 (1): 21–28. doi:10.1097/00004647-200201000-00003. PMID 11807390.
  39. ^ Zhang Z, Sobel RA, Cheng D, Steinberg GK, Yenari MA (November 2001). "Mild hypothermia increases Bcl-2 protein expression following global cerebral ischemia". Brain Research. Molecular Brain Research. 95 (1–2): 75–85. doi:10.1016/S0169-328X(01)00247-9. PMID 11687278.
  40. ^ Wang H, Olivero W, Wang D, Lanzino G (May 2006). "Cold as a therapeutic agent". Acta Neurochirurgica. 148 (5): 565–570. doi:10.1007/s00701-006-0747-z. PMID 16489500. S2CID 25885634.
  41. ^ Little WJ (1966). "On the influence of abnormal parturition, difficult labours, premature birth, and asphyxia neonatorum, on the mental and physical condition of the child, especially in relation to deformities". Clinical Orthopaedics and Related Research. 46 (46): 7–22. doi:10.1097/00003086-196600460-00002. PMID 5950310.
  42. ^ Westin B (October 2006). "Hypothermia in the resuscitation of the neonate: a glance in my rear-view mirror". Acta Paediatrica. 95 (10): 1172–1174. doi:10.1080/08035250600794583. PMID 16982485. S2CID 38525109.
  43. ^ Miller JA (July 1949). "Factors in Neonatal Resistance to Anoxia. I. Temperature and Survival of Newborn Guinea Pigs Under Anoxia". Science. 110 (2848): 113–114. Bibcode:1949Sci...110..113M. doi:10.1126/science.110.2848.113. PMID 17780238.
  44. ^ Enhorning G, Westin B (August 1954). "Experimental studies of the human fetus in prolonged asphyxia". Acta Physiologica Scandinavica. 31 (4): 359–375. doi:10.1111/j.1748-1716.1954.tb01147.x. PMID 13197106.
  45. ^ Westin B, Miller JA, Nyberg R, Wedenberg E (May 1959). "Neonatal asphyxia pallida treated with hypothermia alone or with hypothermia and transfusion of oxygenated blood". Surgery. 45 (5): 868–879. PMID 13659328.
  46. ^ Auld PA, Nelson NM, Nicolopoulos DA, Helwig F, Smith CA (December 1962). "Physiologic studies on an infant in deep hypothermia". The New England Journal of Medicine. 267 (26): 1348–1351. doi:10.1056/NEJM196212272672606. PMID 13965545.
  47. ^ Silverman WA, Fertig JW, Berger AP (November 1958). "The influence of the thermal environment upon the survival of newly born premature infants". Pediatrics. 22 (5): 876–886. doi:10.1542/peds.22.5.876. PMID 13600915. S2CID 37390559.
  48. ^ Elliott RI, Mann TP (February 1957). "Neonatal cold injury due to accidental exposure to cold". Lancet. 272 (6962): 229–234. doi:10.1016/s0140-6736(57)90298-2. PMID 13399181.
  49. ^ Brodie HR, Cross KW, Lomer TR (August 1957). "Heat production in new-born infants under normal and hypoxic conditions". The Journal of Physiology. 138 (1): 156–163. doi:10.1113/jphysiol.1957.sp005843. PMC 1363035. PMID 13463804.
  50. ^ Miller JA, Zakhary R, Miller FS (June 1964). "Hypothermia, Asphyxia, and Cardiac Glycogen in Guinea Pigs". Science. 144 (3623): 1226–1227. Bibcode:1964Sci...144.1226M. doi:10.1126/science.144.3623.1226. PMID 14150326. S2CID 43521244.
  51. ^ Dunn JM, Miller JA (May 1969). "Hypothermia combined with positive pressure ventilation in resuscitation of the asphyxiated neonate. Clinical observations in 28 infants". American Journal of Obstetrics and Gynecology. 104 (1): 58–67. doi:10.1016/s0002-9378(16)34141-2. PMID 4888017.
  52. ^ Ehrström J, Hirvensalo M, Donner M, Hietalahti J (May 1969). "Hypothermia in the resuscitation of severely asphyctic newborn infants. A follow-up study". Annals of Clinical Research. 1 (1): 40–49. PMID 5350770.
  53. ^ Cordey R, Chiolero R, Miller JA (September 1973). "Resuscitation of neonates by hypothermia: report on 20 cases with acid-base determination on 10 cases and the long-term development of 33 cases". Resuscitation. 2 (3): 169–181. doi:10.1016/0300-9572(73)90042-7. PMID 4773063.
  54. ^ Oates RK, Harvey D (July 1976). "Failure of hypothermia as treatment for asphyxiated newborn rabbits". Archives of Disease in Childhood. 51 (7): 512–516. doi:10.1136/adc.51.7.512. PMC 1546031. PMID 989263.
  55. ^ Michenfelder JD, Milde JH (1977). "Failure of prolonged hypocapnia, hypothermia, or hypertension to favorably alter acute stroke in primates". Stroke. 8 (1): 87–91. doi:10.1161/01.str.8.1.87. PMID 402043.
  56. ^ Bohn DJ, Biggar WD, Smith CR, Conn AW, Barker GA (June 1986). "Influence of hypothermia, barbiturate therapy, and intracranial pressure monitoring on morbidity and mortality after near-drowning". Critical Care Medicine. 14 (6): 529–534. doi:10.1097/00003246-198606000-00002. PMID 3709193. S2CID 34347292.
  57. ^ Kopshev SN (1982). "[Craniocerebral hypothermia in the prevention and combined therapy of cerebral pathology in infants with asphyxia neonatorum]". Akusherstvo I Ginekologiia (7): 56–58. PMID 7137497.
  58. ^ Prof Peter Dunn, Bristol, personal communication
  59. ^ Delpy DT, Gordon RE, Hope PL, Parker D, Reynolds EO, Shaw D, Whitehead MD (August 1982). "Noninvasive investigation of cerebral ischemia by phosphorus nuclear magnetic resonance". Pediatrics. 70 (2): 310–313. doi:10.1542/peds.70.2.310. PMID 7099806. S2CID 12319676.
  60. ^ Vannucci RC (April 1990). "Experimental biology of cerebral hypoxia-ischemia: relation to perinatal brain damage". Pediatric Research. 27 (4 Pt 1): 317–326. doi:10.1203/00006450-199004000-00001. PMID 1971436.
  61. ^ Kirino T (May 1982). "Delayed neuronal death in the gerbil hippocampus following ischemia". Brain Research. 239 (1): 57–69. doi:10.1016/0006-8993(82)90833-2. PMID 7093691. S2CID 31592644.
  62. ^ Pulsinelli WA, Brierley JB, Plum F (May 1982). "Temporal profile of neuronal damage in a model of transient forebrain ischemia". Annals of Neurology. 11 (5): 491–498. doi:10.1002/ana.410110509. PMID 7103425. S2CID 25912699.
  63. ^ Hope PL, Costello AM, Cady EB, Delpy DT, Tofts PS, Chu A, et al. (August 1984). "Cerebral energy metabolism studied with phosphorus NMR spectroscopy in normal and birth-asphyxiated infants". Lancet. 2 (8399): 366–370. doi:10.1016/s0140-6736(84)90539-7. PMID 6147452. S2CID 31985414.
  64. ^ Olney JW, Sharpe LG (October 1969). "Brain lesions in an infant rhesus monkey treated with monsodium glutamate". Science. 166 (3903): 386–388. Bibcode:1969Sci...166..386O. doi:10.1126/science.166.3903.386. PMID 5812037. S2CID 24563713.
  65. ^ Olney JW, Ho OL (August 1970). "Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine". Nature. 227 (5258): 609–611. Bibcode:1970Natur.227..609O. doi:10.1038/227609b0. PMID 5464249. S2CID 4201118.
  66. ^ Simon RP, Swan JH, Griffiths T, Meldrum BS (November 1984). "Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain". Science. 226 (4676): 850–852. Bibcode:1984Sci...226..850S. doi:10.1126/science.6093256. PMID 6093256.
  67. ^ Kerr JF, Wyllie AH, Currie AR (August 1972). "Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics". British Journal of Cancer. 26 (4): 239–257. doi:10.1038/bjc.1972.33. PMC 2008650. PMID 4561027.
  68. ^ Ellis HM, Horvitz HR (March 1986). "Genetic control of programmed cell death in the nematode C. elegans". Cell. 44 (6): 817–829. doi:10.1016/0092-8674(86)90004-8. PMID 3955651. S2CID 44031839.
  69. ^ Raff MC (April 1992). "Social controls on cell survival and cell death". Nature. 356 (6368): 397–400. Bibcode:1992Natur.356..397R. doi:10.1038/356397a0. PMID 1557121. S2CID 4314492.
  70. ^ Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, et al. (April 1992). "Induction of apoptosis in fibroblasts by c-myc protein". Cell. 69 (1): 119–128. doi:10.1016/0092-8674(92)90123-T. PMID 1555236. S2CID 32836480.
  71. ^ Mehmet H, Yue X, Squier MV, Lorek A, Cady E, Penrice J, et al. (November 1994). "Increased apoptosis in the cingulate sulcus of newborn piglets following transient hypoxia-ischaemia is related to the degree of high energy phosphate depletion during the insult". Neuroscience Letters. 181 (1–2): 121–125. doi:10.1016/0304-3940(94)90574-6. PMID 7898750. S2CID 44935480.
  72. ^ Beilharz EJ, Williams CE, Dragunow M, Sirimanne ES, Gluckman PD (March 1995). "Mechanisms of delayed cell death following hypoxic-ischemic injury in the immature rat: evidence for apoptosis during selective neuronal loss". Brain Research. Molecular Brain Research. 29 (1): 1–14. doi:10.1016/0169-328X(94)00217-3. PMID 7769986.
  73. ^ Edwards AD, Yue X, Cox P, Hope PL, Azzopardi DV, Squier MV, Mehmet H (November 1997). "Apoptosis in the brains of infants suffering intrauterine cerebral injury". Pediatric Research. 42 (5): 684–689. doi:10.1203/00006450-199711000-00022. PMID 9357944.
  74. ^ Northington FJ, Graham EM, Martin LJ (December 2005). "Apoptosis in perinatal hypoxic-ischemic brain injury: how important is it and should it be inhibited?". Brain Research. Brain Research Reviews. 50 (2): 244–257. doi:10.1016/j.brainresrev.2005.07.003. PMID 16216332. S2CID 34368053.
  75. ^ Stone BS, Zhang J, Mack DW, Mori S, Martin LJ, Northington FJ (November 2008). "Delayed neural network degeneration after neonatal hypoxia-ischemia". Annals of Neurology. 64 (5): 535–546. doi:10.1002/ana.21517. PMC 2605201. PMID 19067347.
  76. ^ Thiringer K, Hrbek A, Karlsson K, Rosén KG, Kjellmer I (July 1987). "Postasphyxial cerebral survival in newborn sheep after treatment with oxygen free radical scavengers and a calcium antagonist". Pediatric Research. 22 (1): 62–66. doi:10.1203/00006450-198707000-00015. PMID 3627874.
  77. ^ Hagberg H, Andersson P, Kjellmer I, Thiringer K, Thordstein M (August 1987). "Extracellular overflow of glutamate, aspartate, GABA and taurine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia". Neuroscience Letters. 78 (3): 311–317. doi:10.1016/0304-3940(87)90379-X. PMID 2888062. S2CID 23222078.
  78. ^ McDonald JW, Silverstein FS, Johnston MV (August 1987). "MK-801 protects the neonatal brain from hypoxic-ischemic damage". European Journal of Pharmacology. 140 (3): 359–361. doi:10.1016/0014-2999(87)90295-0. hdl:2027.42/26610. PMID 2820765.
  79. ^ Blumberg RM, Cady EB, Wigglesworth JS, McKenzie JE, Edwards AD (January 1997). "Relation between delayed impairment of cerebral energy metabolism and infarction following transient focal hypoxia-ischaemia in the developing brain". Experimental Brain Research. 113 (1): 130–137. doi:10.1007/BF02454148. PMID 9028781. S2CID 24918003.
  80. ^ Williams CE, Gunn AJ, Mallard C, Gluckman PD (January 1992). "Outcome after ischemia in the developing sheep brain: an electroencephalographic and histological study". Annals of Neurology. 31 (1): 14–21. doi:10.1002/ana.410310104. PMID 1543346. S2CID 30706281.
  81. ^ Clemence M, Thornton JS, Penrice J, Amess P, Punwani S, Tyszczuk L, et al. (1996). "31P MRS and quantitative diffusion and T2 MRI show no cerebroprotective effects of intravenous MgSO4 after severe transient hypoxia-ischaemia in the neonatal piglet". MAGMA. 4: 114.
  82. ^ Gunn AJ, Mydlar T, Bennet L, Faull RL, Gorter S, Cook C, et al. (June 1989). "The neuroprotective actions of a calcium channel antagonist, flunarizine, in the infant rat". Pediatric Research. 25 (6): 573–576. doi:10.1203/00006450-198906000-00003. PMID 2740146.
  83. ^ Marks KA, Mallard CE, Roberts I, Williams CE, Gluckman PD, Edwards AD (August 1996). "Nitric oxide synthase inhibition attenuates delayed vasodilation and increases injury after cerebral ischemia in fetal sheep". Pediatric Research. 40 (2): 185–191. doi:10.1203/00006450-199608000-00002. PMID 8827765.
  84. ^ Gluckman P, Klempt N, Guan J, Mallard C, Sirimanne E, Dragunow M, et al. (January 1992). "A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury". Biochemical and Biophysical Research Communications. 182 (2): 593–599. doi:10.1016/0006-291X(92)91774-K. PMID 1370886.
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