Neonatal hypoxia-ischemia induces attention-deficit hyperactivity disorder-like behavior in rats.

Abstract

Attention-deficit hyperactivity disorder (ADHD) may be caused by genetic or environmental factors. Among environmental factors, perinatal complications are related, such as neonatal hypoxia-ischemia (HI). Thus, the aim of this study was to investigate whether HI contributes to the development of characteristics related to ADHD in adult rats, and to correlate the behavioral results with brain damage volume. Male Wistar rats were divided into 2 groups: HI and control. The HI procedure consisted of a permanent occlusion of the right common carotid artery followed by a period of hypoxia (90 min; 8% O₂ and 92% N₂) on the 7th postnatal day. Two months later, animals were evaluated in the open field test during a single 5-min session, and in the 5-choice serial reaction time task (5-CSRTT), over 25 weeks. Our results demonstrated that animals submitted to HI manifest cognitive impairments in task acquisition, deficits in sustained attention, and increases in impulsivity and compulsivity in response to task manipulation in the 5-CSRTT. Locomotor activity observed in open field did not differ between groups. Moreover, brain volume loss in the total hemisphere, cerebral cortex, white matter, hippocampus, and striatum were observed in HI animals, especially on the side ipsilateral to the lesion. From these results, we can infer that neonatal HI is an environmental factor that could contribute to the development of behavioral characteristics observed in ADHD that are associated with general brain atrophy.

Prenatal smoking exposure and neuropsychiatric comorbidity of ADHD: a finnish nationwide population-based cohort study

“…This hypothesis is supported by a previous finding of a linear correlation between number of cigarettes smoked during pregnancy and severity of attentional problems [36]. The dose-response-effect could be mediated by chronic hypoxia to the fetal brain as animal models have demonstrated association between neonatal hypoxia and ADHD-like behavior [15]. The fetal brain could also be more vulnerable to smoking exposure in the later periods of pregnancy.…”

“…The possibility of the teratogenic effects of smoking as a cause of ADHD should be considered, because some animal models suggest in utero nicotine exposure to be associated with neuronal cell death [13]. Smoking during pregnancy has been represented to associate with gestational hypoxia [14] and gestational hypoxia has been suggested to contribute to ADHD-like symptoms [15]. Maternal smoking during pregnancy has also been associated with increased offspring risk for several psychiatric conditions, such as pervasive developmental disorders [16], conduct disorders [17] and depression [18].…”

Therapeutic Hypothermia Provides Variable Protection against Behavioral Deficits after Neonatal Hypoxia-Ischemia: A Potential Role for Brain-Derived Neurotrophic Factor

“…Although, rodents injured by HI manifest cognitive impairments, attention deficits, and increased impulsivity and compulsivity [65–67]; the protection reported by TH is contradictory [19,21,24,68–74]. These contradictions may arise from the lack of proper standardization in behavioral testing in immature rodents, the variable protocols of TH used, and the effects of other biological variables such as sex and growth.…”

Models of hypoxia and ischemia-induced seizures

“…Moreover, performance in the 8 arm radial maze was assessed starting at week 7 and week 16 with a greater deficit found at the later time point. Tests of attention have revealed deficits as well with HI treated animals performing poorly on the 5 choice serial reaction time test (Miguel et al, 2015;Smith et al, 2014a). One feature noted in the clinical data regarding the long-term outcome of neonates suffering HI insult is that males tend to have a worse cognitive outcome than females.…”