Preconditioning and postinsult therapies for perinatal hypoxic-ischemic injury at term.
Perinatal hypoxic-ischemic encephalopathy can be a devastating complication of childbirth. Herein, the authors review the pathophysiology of hypoxic-ischemic encephalopathy and the current status of neuroprotective strategies to ameliorate the injury centering on four themes: (1) monitoring in the perinatal period, (2) rapid identification of affected neonates to allow timely institution of therapy, (3) preconditioning therapy (a therapeutic that reduces the brain vulnerability) before hypoxic-ischemic encephalopathy, and (4) prompt institution of postinsult therapies to ameliorate the evolving injury. Recent clinical trials have demonstrated the significant benefit for hypothermic therapy in the postnatal period; furthermore, there is accumulating preclinical evidence that adjunctive therapies can enhance hypothermic neuroprotection. Advances in the understanding of preconditioning may lead to the administration of neuroprotective agents earlier during childbirth. Although most of these neuroprotective strategies have not yet entered clinical practice, there is a significant hope that further developments will enhance hypothermic neuroprotection.
Departments of Anaesthetics, Medical Research Council Clinical Sciences Centre, Queen Charlotte's & Chelsea Hospital, Imperial College London, London, United Kingdom.
Robert D
RD
Sanders
Helen J
HJ
Manning
Nicola J
NJ
Robertson
Daqing
D
Ma
A David
AD
Edwards
Henrik
H
Hagberg
Mervyn
M
Maze
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis; D004921:Erythropoietin / Q000627:therapeutic use; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D018496:Hyperoxia / Q000517:prevention & control; D016857:Hypocapnia / Q000517:prevention & control; D020925:Hypoxia-Ischemia, Brain / Q000151:congenital* / Q000209:etiology / Q000628:therapy*; D007249:Inflammation / Q000150:complications; D019194:Ischemic Preconditioning / Q000379:methods*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000150:complications / Q000188:drug therapy
D000316:Adrenergic alpha-Agonists; D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; D000975:Antioxidants; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D004921:Erythropoietin