brain hypoxia ischemia


Summary: A disorder characterized by a reduction of oxygen in the blood combined with reduced blood flow (ISCHEMIA) to the brain from a localized obstruction of a cerebral artery or from systemic hypoperfusion. Prolonged hypoxia-ischemia is associated with ISCHEMIC ATTACK, TRANSIENT; BRAIN INFARCTION; BRAIN EDEMA; COMA; and other conditions.

Top Publications

  1. Leonardo C, Hall A, Collier L, Gottschall P, Pennypacker K. Inhibition of gelatinase activity reduces neural injury in an ex vivo model of hypoxia-ischemia. Neuroscience. 2009;160:755-66 pubmed publisher
    ..These data, coupled with the effectiveness of these compounds previously shown in vivo, support the selective targeting of gelatin-degrading MMPs and activated microglia as potential therapeutic approaches to combat neonatal H-I injury. ..
  2. Azzopardi D, Strohm B, Edwards A, Dyet L, Halliday H, Juszczak E, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361:1349-58 pubmed publisher
    ..Current Controlled Trials number, ISRCTN89547571.) ..
  3. Azzopardi D, Strohm B, Edwards A, Halliday H, Juszczak E, Levene M, et al. Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial. Arch Dis Child Fetal Neonatal Ed. 2009;94:F260-4 pubmed publisher
    ..Treatment with hypothermia may have prevented the worsening of the encephalopathy that is commonly observed following asphyxia. ..
  4. Gunn A, Wyatt J, Whitelaw A, Barks J, Azzopardi D, Ballard R, et al. Therapeutic hypothermia changes the prognostic value of clinical evaluation of neonatal encephalopathy. J Pediatr. 2008;152:55-8, 58.e1 pubmed
    ..006) compared with standard care (12/33, 36%). Infants with moderate encephalopathy on day 4 may have a more favorable prognosis after hypothermia treatment than expected after standard care. ..
  5. Okereafor A, Allsop J, Counsell S, Fitzpatrick J, Azzopardi D, Rutherford M, et al. Patterns of brain injury in neonates exposed to perinatal sentinel events. Pediatrics. 2008;121:906-14 pubmed publisher
    ..Affected infants did not seem intrinsically different from our low-risk population. These data support the need for anticipating sentinel events and expediting delivery. ..
  6. Shankaran S, Pappas A, Laptook A, McDonald S, Ehrenkranz R, Tyson J, et al. Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy. Pediatrics. 2008;122:e791-8 pubmed publisher
    ..Although not powered to test these secondary outcomes, whole-body hypothermia in infants with encephalopathy was safe and was associated with a consistent trend for decreasing frequency of each of the components of disability. ..
  7. Gunn A, Hoehn T, Hansmann G, Buhrer C, Simbruner G, Yager J, et al. Hypothermia: an evolving treatment for neonatal hypoxic ischemic encephalopathy. Pediatrics. 2008;121:648-9; author reply 649-50 pubmed publisher
  8. Carty M, Wixey J, Colditz P, Buller K. Post-insult minocycline treatment attenuates hypoxia-ischemia-induced neuroinflammation and white matter injury in the neonatal rat: a comparison of two different dose regimens. Int J Dev Neurosci. 2008;26:477-85 pubmed publisher
  9. Girard S, Kadhim H, Larouche A, Roy M, Gobeil F, Sebire G. Pro-inflammatory disequilibrium of the IL-1 beta/IL-1ra ratio in an experimental model of perinatal brain damages induced by lipopolysaccharide and hypoxia-ischemia. Cytokine. 2008;43:54-62 pubmed publisher
    ..The resulting pro-inflammatory orientation in the IL-1/IL-1ra balance might play a role in the initiation of perinatal brain damages. ..

More Information


  1. Leonardo C, Eakin A, Ajmo J, Collier L, Pennypacker K, Strongin A, et al. Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat. J Neuroinflammation. 2008;5:34 pubmed publisher
    ..Thus, MMP-2 and MMP-9 may be viable therapeutic targets to treat neonatal brain injury. ..
  2. Koike M, Shibata M, Tadakoshi M, Gotoh K, Komatsu M, Waguri S, et al. Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am J Pathol. 2008;172:454-69 pubmed publisher
  3. Zanelli S, Naylor M, Dobbins N, Quigg M, Goodkin H, Matsumoto J, et al. Implementation of a 'Hypothermia for HIE' program: 2-year experience in a single NICU. J Perinatol. 2008;28:171-5 pubmed
    ..While lowering the body temperature of encephalopathic newborns is not difficult, addressing the complex medical problems of this vulnerable group of patients requires an experienced multidisciplinary team in regional referral centers. ..
  4. Kakita T, Nagatoya K, Takimoto H, Matsuda H, Mori T, Kawaguchi A, et al. Antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis with membranous nephropathy treated using thiamazole. CEN Case Rep. 2013;2:165-169 pubmed publisher
    ..The histopathologic results showed that immunosuppressive therapy seemed to be effective in treating crescentic glomerulonephritis; furthermore, it reduced proteinuria but could not reduce the MPO-ANCA titer. ..
  5. Mukai T, Mori Y, Shimazu T, Takahashi A, Tsunoda H, Yamaguchi S, et al. Intravenous injection of umbilical cord-derived mesenchymal stromal cells attenuates reactive gliosis and hypomyelination in a neonatal intraventricular hemorrhage model. Neuroscience. 2017;355:175-187 pubmed publisher
    ..These results suggest UC-MSCs attenuate neonatal IVH by protecting gliosis and apoptosis of the injured brain, and intravenous injection of UC-MSCs cultured in RM may be feasible for neonatal IVH in clinic. ..
  6. Luo L, Xiong Y, Wang H. [Expression of GRP78 and caspase-12 in neonatal rats with experimental hypoxic-ischemic white matter damage]. Zhongguo Dang Dai Er Ke Za Zhi. 2009;11:691-4 pubmed
    ..This suggests that endoplasmic reticulum stress may be induced following HI. Endoplasmic reticulum stress seems to be involved in the apoptosis of oligodendrocytes induced by HI in neonatal rats with WMD. ..
  7. Khashana A, Ahmed E. Hyperdehydroepiandrosterone in neonates with hypoxic ischemic encephalopathy and circulatory collapse. Pediatr neonatol. 2017;58:504-508 pubmed publisher
  8. Rodriguez Alvarez N, Jimenez Mateos E, Dunleavy M, Waddington J, Boylan G, Henshall D. Effects of hypoxia-induced neonatal seizures on acute hippocampal injury and later-life seizure susceptibility and anxiety-related behavior in mice. Neurobiol Dis. 2015;83:100-14 pubmed publisher
  9. Xu T, Xu N, Yang Z, Wan Y, Wu Q, Huang K. Neuroprotective effects of electroacupuncture on hypoxic-ischemic encephalopathy in newborn rats are associated with increased expression of GDNF-RET and protein kinase B. Chin J Integr Med. 2016;22:457-66 pubmed publisher
    ..EA has neuroprotective effects on HIE and could be a potential therapeutic strategy for HIE in the neonate. Activation of RET/Akt signaling pathway might be involved in this process. ..
  10. Judge S, Smith P. Patents related to therapeutic activation of K(ATP) and K(2P) potassium channels for neuroprotection: ischemic/hypoxic/anoxic injury and general anesthetics. Expert Opin Ther Pat. 2009;19:433-60 pubmed publisher
  11. Oyama N, Yagita Y, Sasaki T, Omura Matsuoka E, Terasaki Y, Sugiyama Y, et al. An angiotensin II type 1 receptor blocker can preserve endothelial function and attenuate brain ischemic damage in spontaneously hypertensive rats. J Neurosci Res. 2010;88:2889-98 pubmed publisher
    ..These findings indicate that chronic prehypertensive treatment with olmesartan could attenuate brain ischemic injury through the maintenance of endothelial function in the cerebral cortex in SHR. ..
  12. Massaro A, Rais Bahrami K, Chang T, Glass P, Short B, Baumgart S. Therapeutic hypothermia for neonatal encephalopathy and extracorporeal membrane oxygenation. J Pediatr. 2010;157:499-501, 501.e1 pubmed publisher
    ..In all 5 infants, systemic hypothermia was maintained during ECMO with acceptable clinical outcomes. ..
  13. Yang J, Liu J, Niu G, Liu Y, Wu E. Magnetic resonance imaging of migrating neuronal precursors in normal and hypoxic-ischemic neonatal rat brains by intraventricular MPIO labeling. Conf Proc IEEE Eng Med Biol Soc. 2008;2008:363-6 pubmed publisher
  14. Björkman S, Miller S, Rose S, Burke C, Colditz P. Seizures are associated with brain injury severity in a neonatal model of hypoxia-ischemia. Neuroscience. 2010;166:157-67 pubmed publisher
    ..In conclusion we report that both sub-clinical and clinical seizures are associated with increased severity of H/I injury in a term model of neonatal H/I. ..
  15. Hwang I, Yoo K, Han T, Lee C, Choi J, Yi S, et al. Enhanced cell proliferation and neuroblast differentiation in the rat hippocampal dentate gyrus following myocardial infarction. Neurosci Lett. 2009;450:275-80 pubmed publisher
    ..In addition, DCX-positive processes were prominent in the MI group. These results suggest that MI may influence cell proliferation and affect neuroblast differentiation in the subgranular zone of the DG. ..
  16. Fang M, Jiang H, Ye L, Cai C, Hu Y, Pan S, et al. Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats. Oncotarget. 2017;8:75308-75325 pubmed publisher
    ..Our study indicates that metformin treatment protects against neonatal hypoxic-ischemic brain injury and thus has potential as a therapy for this disease. ..
  17. Samoilova M, Weisspapir M, Abdelmalik P, Velumian A, Carlen P. Chronic in vitro ketosis is neuroprotective but not anti-convulsant. J Neurochem. 2010;113:826-35 pubmed publisher
  18. Sahni P, Zhang J, Sosunov S, Galkin A, Niatsetskaya Z, Starkov A, et al. Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice. Pediatr Res. 2017;: pubmed publisher
    ..Our study provides a critical piece of support for existence of the RET-dependent mechanism of elevated ROS production in reperfusion.Pediatric Research advance online publication 6 December 2017. doi:10.1038/pr.2017.277...
  19. Szakmar E, Kovacs K, Méder Ü, Nagy A, Szell A, Bundzsity B, et al. Feasibility and Safety of Controlled Active Hypothermia Treatment During Transport in Neonates With Hypoxic-Ischemic Encephalopathy. Pediatr Crit Care Med. 2017;18:1159-1165 pubmed publisher
    ..To evaluate the feasibility and safety of controlled active hypothermia versus standard intensive care during neonatal transport in patients with hypoxic-ischemic encephalopathy...
  20. de Vries L, Jongmans M. Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2010;95:F220-4 pubmed publisher
    ..It is therefore recommended to perform follow-up assessment into childhood in children with and without adverse neurological outcome in early infancy. ..
  21. Juul S, Beyer R, Bammler T, McPherson R, Wilkerson J, Farin F. Microarray analysis of high-dose recombinant erythropoietin treatment of unilateral brain injury in neonatal mouse hippocampus. Pediatr Res. 2009;65:485-92 pubmed publisher
  22. Kurinczuk J, White Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010;86:329-38 pubmed publisher
    ..It is estimated that 30% of cases of NE in developed populations and 60% in developing populations have some evidence of intrapartum hypoxic-ischaemia. ..
  23. Palibrk V, Suganthan R, Scheffler K, Wang W, Bjørås M, Bøe S. PML regulates neuroprotective innate immunity and neuroblast commitment in a hypoxic-ischemic encephalopathy model. Cell Death Dis. 2016;7:e2320 pubmed publisher
    ..The data demonstrate a dual role of PML in protection and recovery after brain injury. ..
  24. Harding B, Conception K, Li Y, Zhang L. Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE). Int J Mol Sci. 2016;18: pubmed publisher
  25. Sekhon M, Ainslie P, Griesdale D. Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a "two-hit" model. Crit Care. 2017;21:90 pubmed publisher
    ..We provide an in-depth review of the pathophysiology of HIBI to critically evaluate current approaches for the early treatment of HIBI secondary to CA. Potential therapeutic targets and future research directions are summarized. ..
  26. Goñi de Cerio F, Alvarez A, Alvarez F, Rey Santano M, Alonso Alconada D, Mielgo V, et al. MgSO4 treatment preserves the ischemia-induced reduction in S-100 protein without modification of the expression of endothelial tight junction molecules. Histol Histopathol. 2009;24:1129-38 pubmed publisher
    ..We speculate that MgSO4 treatment confers neuroprotection by restoration of blood brain permeability in hypoxia-ischemia. ..
  27. Monteith C, Flood K, Mullers S, Unterscheider J, Breathnach F, Daly S, et al. Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses. Am J Obstet Gynecol. 2017;216:285.e1-285.e6 pubmed publisher
    ..Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome. ..
  28. Robertson N, Kendall G, Thayyil S. Techniques for therapeutic hypothermia during transport and in hospital for perinatal asphyxial encephalopathy. Semin Fetal Neonatal Med. 2010;15:276-86 pubmed publisher
    ..We describe our experience of passive cooling before and during the transfer of infants with encephalopathy to cooling centres in a major city in the UK. ..
  29. Kelen D, Robertson N. Experimental treatments for hypoxic ischaemic encephalopathy. Early Hum Dev. 2010;86:369-77 pubmed publisher
    ..Finally, potential future therapies such as regeneration/repair and postconditioning are discussed. ..
  30. Azzopardi D. Clinical management of the baby with hypoxic ischaemic encephalopathy. Early Hum Dev. 2010;86:345-50 pubmed publisher
    ..This article is a summary of the in hospital clinical management of infants with hypoxic ischaemic encephalopathy. ..
  31. Groenendaal F, Hukkelhoven C, de Vries L, van Bel F. [Neuroprotection using hypothermia after perinatal asphyxia in full-term neonates]. Ned Tijdschr Geneeskd. 2008;152:2210-2 pubmed
    ..Treatment should be started within 6 hours after birth. An estimated 180-200 neonates may be eligible for this novel approach to neuroprotection each year in the Netherlands. ..
  32. Iwai M, Stetler R, Xing J, Hu X, Gao Y, Zhang W, et al. Enhanced oligodendrogenesis and recovery of neurological function by erythropoietin after neonatal hypoxic/ischemic brain injury. Stroke. 2010;41:1032-7 pubmed publisher
    ..These effects likely contribute to the observed improvement in neurological functional outcomes. ..
  33. Wilkinson D. Cool heads: ethical issues associated with therapeutic hypothermia for newborns. Acta Paediatr. 2009;98:217-20 pubmed publisher
    ..Hypothermia is a promising new therapy, but further research will be necessary to help resolve some of the ethical concerns associated with its use in newborns with HIE . ..
  34. Moresco L, Bellissima V, Colivicchi M, Crivelli S, Guerriero F, Ricotti A, et al. [Markers of brain injury in non-invasive biological fluids]. Minerva Pediatr. 2010;62:141-3 pubmed
    ..The present article is aimed at investigating the role of dosage biochemical markers in non-invasive biological fluids such as S100B, a calcium binding protein, activin A, a protein expressed in Central nervous System (CNS). ..
  35. van der Kooij M, Nijboer C, Ohl F, Groenendaal F, Heijnen C, van Bel F, et al. NF-kappaB inhibition after neonatal cerebral hypoxia-ischemia improves long-term motor and cognitive outcome in rats. Neurobiol Dis. 2010;38:266-72 pubmed publisher
    ..In conclusion, the almost complete reduction in lesion size observed after TAT-NBD treatment was associated with long-lasting normalization of sensorimotor and cognitive functions. ..
  36. Murray D, Boylan G, Ryan C, Connolly S. Early EEG findings in hypoxic-ischemic encephalopathy predict outcomes at 2 years. Pediatrics. 2009;124:e459-67 pubmed publisher
    ..Early EEG is a reliable predictor of outcome in HIE. A normal or mildly abnormal EEG results within 6 hours after birth were associated with normal neurodevelopmental outcomes at 24 months. ..
  37. Albanna E, Ahmed H. Circulating Dickkopf-1 in hypoxic ischemic neonates. J Matern Fetal Neonatal Med. 2016;29:2171-5 pubmed publisher
    ..Serum DKK-1 levels increased significantly in severe HIE patients. Our study provides for the first time the evidence of releasing Dkk-1 into the circulation of neonates with HIE with higher level in severe degree. ..
  38. Jung W, Im G, Chung J, Ahn S, Jeon T, Chang Y, et al. Neuroplasticity for spontaneous functional recovery after neonatal hypoxic ischemic brain injury in rats observed by functional MRI and diffusion tensor imaging. Neuroimage. 2016;126:140-50 pubmed publisher
  39. Chao D, Xia Y. Ionic storm in hypoxic/ischemic stress: can opioid receptors subside it?. Prog Neurobiol. 2010;90:439-70 pubmed publisher
  40. Oksala N, Jokinen H, Melkas S, Oksala A, Pohjasvaara T, Hietanen M, et al. Cognitive impairment predicts poststroke death in long-term follow-up. J Neurol Neurosurg Psychiatry. 2009;80:1230-5 pubmed publisher
    ..63, p = 0.0123). In patients with ischaemic stroke, cognitive impairment, particularly in executive functions, and visuospatial/constructional abilities relate to poor survival. ..
  41. Jenny B, Kanemitsu M, Tsupykov O, Potter G, Salmon P, Zgraggen E, et al. Fibroblast growth factor-2 overexpression in transplanted neural progenitors promotes perivascular cluster formation with a neurogenic potential. Stem Cells. 2009;27:1309-17 pubmed publisher
  42. Wang A, Huang C, Chang W, Chen W. Bispectral index monitoring in subarachnoid hemorrhage-associated out-of hospital cardiac arrest. Am J Emerg Med. 2016;34:934.e1-3 pubmed publisher
    ..This was confirmed by brain perfusion scan and standard electroencephalographic study. Using BIS, we can identify patients with poor neurologic outcome earlier, and treatment could be alleviated if prognosis is futile. ..
  43. Zou R, Mu D. [Prevention and treatment of energy failure in neonates with hypoxic-ischemic encephalopathy]. Zhongguo Dang Dai Er Ke Za Zhi. 2016;18:915-920 pubmed
    ..As an important link in the course of HIE, energy failure greatly affects the development and progression of HIE. This article reviews the research advances in the treatment and prevention of energy failure in the course of HIE. ..
  44. Kumari R, Willing L, Patel S, Krady J, Zavadoski W, Gibbs E, et al. The PPAR-gamma agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse. J Cereb Blood Flow Metab. 2010;30:352-60 pubmed publisher
  45. Mao J. [Patterns of brain injury in neonatal hypoxic-ischemic encephalopathy on magnetic resonance imaging: recommendations on classification]. Zhongguo Dang Dai Er Ke Za Zhi. 2017;19:1225-1233 pubmed
    ..It is worth noting that sometimes the pattern of brain injury among those described above cannot be determined exactly, but rather a predominant one is identified; not all cases of HIE have characteristic MRI findings...
  46. Wu C, Huang J, Hsia S, Lee H, Lin J. Pott's puffy tumor after acupuncture therapy. Eur J Pediatr. 2009;168:1147-9 pubmed publisher
    ..It presents as a localised swelling of the forehead. This paper describes a 12-year-old girl with PPT. To our knowledge, this is the first case report of PTT caused by acupuncture therapy. ..
  47. Simiyu I, Mchaile D, Katsongeri K, Philemon R, Msuya S. Prevalence, severity and early outcomes of hypoxic ischemic encephalopathy among newborns at a tertiary hospital, in northern Tanzania. BMC Pediatr. 2017;17:131 pubmed publisher
    ..Good obstetric care and immediate resuscitation of newborns are vital in reducing the occurrence of HIE and improving the general outcome of newborns. ..
  48. Zhang W, Hu X, Yang W, Gao Y, Chen J. Omega-3 polyunsaturated fatty acid supplementation confers long-term neuroprotection against neonatal hypoxic-ischemic brain injury through anti-inflammatory actions. Stroke. 2010;41:2341-7 pubmed publisher
    ..Our results suggest that omega-3 polyunsaturated fatty acids confer potent neuroprotection against neonatal H/I brain injury through, at least partially, suppressing a microglial-mediated inflammatory response. ..
  49. Baburamani A, Hurling C, Stolp H, Sobotka K, Gressens P, Hagberg H, et al. Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury. Int J Mol Sci. 2015;16:22509-26 pubmed publisher
    ..Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury. ..
  50. Cirelli I, Bickle Graz M, Tolsa J. Comparison of Griffiths-II and Bayley-II tests for the developmental assessment of high-risk infants. Infant Behav Dev. 2015;41:17-25 pubmed publisher
    ..8. The meaning of the results for a given child was the same for the two tests. Two scores were interchangeable, the Griffiths-II QD and the BSID-II MDI. ..
  51. Joo S, Kim T, Seo B, Lee J, Kim J, Kim S, et al. The clinical utility of the Kopitnik arteriovenous malformation microclip during STA-MCA bypass surgery. Acta Neurochir (Wien). 2010;152:547-51 pubmed publisher
    ..The Kopitnik AVM microclip appears to be clinically effective and safe for EC-IC bypass surgery, especially when smaller vessels are involved. ..
  52. Cotten C, Goldstein R, McDonald S, Goldberg R, Salhab W, Carlo W, et al. Apolipoprotein E genotype and outcome in infants with hypoxic-ischemic encephalopathy. Pediatr Res. 2014;75:424-30 pubmed publisher
    ..None of the differences were statistically significant. CP prevalence was also similar among genotype groups. Disability was not associated with the APOE genotype in this cohort of HIE survivors. ..