Combination Therapy of Hypothermia for Hypoxic Encephalopathy in Neonates
Pp. 35-71 (37)
Renjith Kalikkot Thekkeveedu, Abhay Bhatt, Sumana Ramarao, Zhengwei Cai and Yi Pang
Perinatal brain injury remains a leading cause of mortality and morbidity in
children. Neonatal encephalopathy (NE), which is primarily caused by hypoxicischemic
(HI) events known as hypoxic-ischemic encephalopathy (HIE), is the
predominant form of brain injury in term infants. NIE leads to high mortality and high
incidence of sustained childhood disabilities among survivors.
The past three decades witnessed significant progress towards a deep understanding of
cellular and molecular mechanisms underlying HI-induced brain injury, yet basic
research findings remain to be translated into clinical practice. Currently, the only
available treatment option for HIE is therapeutic hypothermia, also known as targeted
temperature management (TTM). Despite the successful translation from basic research
into clinical use, TTM has several serious limitations including a narrow window of
opportunity and a moderate efficacy leaving about 40-50% of treated infants still die or
suffer from a significant neurologic disability. Hence, there is an urgent need to explore
combined therapies which should broaden the therapeutic window and/or enhance
therapeutic efficacy. In this chapter, we discussed several classes of neuroprotectants
that showed promise in pre- and/or clinical settings.
The first half of this chapter reviews advances in recent development of basic and
clinical research in TTM, including major clinical trials. The second half focuses on
potential candidate therapies to be combined with hypothermia.
Antioxidant, Brain injury, Cerebral palsy, Clinical trial, Cooling,
Delayed neuronal death, Excitatory amino acids, Erythropoietin (EPO), Hypoxicischemic
encephalopathy (HIE), Hypothermia, Targeted temperature management
(TTM), Neonate, Melatonin, Insulin-like growth factor-1 (IGF-1), Xenon, Stem
cell, Neuroinflammation, Neuroprotection, Survival.
Department of Pediatrics, Division of Neonatology, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS39216-4505, USA.