Neonatal Hypoxia, Hippocampal Atrophy, and Memory Impairment: Evidence of a Causal Sequence

Abstract

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life.

Effect of temperature on FAD and NADH-derived signals and neurometabolic coupling in the mouse auditory and motor cortex

“…However, hippocampus had a highest oxidative capacity which could be because of its higher metabolic demands, as previously observed [36,47]. Such effects made the hippocampus more vulnerable to the hypoxic insults, a result which is supported by previous studies [12,75]. The current study showed the positive impact of hypothermia to normalize the redox ratio under hypoxia, which implicated the protective role of hypothermia against oxidative insults.…”

Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior

“…Stepwise linear regression models revealed that the cohort's hippocampal volumes were predictive of some degree of memory impairment. In addition, the gestational age at the treatment was also predictive of hippocampal volumes losses: the younger the age, the greater the atrophy (Cooper, Gadian et al 2013), specially considering critical periods of development.…”

“…In humans, the relationship between hippocampal atrophy, memory impairments and neonatal anoxia has already been described (Bachevalier and Vargha-Khadem 2005;Cooper, Gadian et al 2013). In rodents, correlations between hippocampal atrophy and oxygen deprivation have been described in stroke models (Shrivastava, Chertoff et al 2012).…”

“…Its long-lasting effects include behavioral and cognitive alterations, such as spatial memory and learning deficits, among others (Galeano, Blanco Calvo et al 2011;Cooper, Gadian et al 2013;Galeano, Blanco et al 2014;Takada, dos Santos Haemmerle et al 2015). The developing brain is extremely sensitive to reduction in oxygen supply and the hippocampus, a key region related to learning and memory, is one of the most vulnerable regions of the anoxic brain (Buwalda, Nyakas et al 1995;Vexler and Ferriero 2001;Peterson, Larson et al 2012;Takada, dos Santos Haemmerle et al 2015).…”

Extent of hippocampal atrophy predicts degree of deficit in recall

“…Using the D&P test (10), we assessed the memory ability of 29 patients (mean age, 16:2; range, 9-33 y; 12 females), who had sustained (i) hypoxic/ischemic episodes in the neonatal and/or perinatal period (see Table 1 for details) and (ii) HV reduction greater than 10% of the mean HV of a group of 65 healthy controls (11). (One female patient suffered respiratory failure at age 12, which is thought to be the cause of the hippocampal damage.…”