Sex differences in brain MRI abnormalities and neurodevelopmental outcomes in a rat model of neonatal hypoxia-ischemia

Huang, Huizhi; Wen, Xuerong; Hui, Lisa

doi:10.3109/00207454.2015.1047016

Cited by 29 publications

(22 citation statements)

References 58 publications

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“…Some studies using HI have shown an effect associated with sex [18][19][20]. Here, when we compared injury scores of male and female mice, we found CD1 males to be more injured than females at P7, but no difference between CD1 males and females at P9 ( Fig.…”

Section: Sex Differencessupporting

confidence: 49%

Strain-Related Differences in Mouse Neonatal Hypoxia-Ischemia

2018

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Neonatal hypoxic-ischemic brain injury is commonly studied by means of the Vannucci procedure in mice or rats (unilateral common carotid artery occlusion followed by hypoxia). Previously, we modified the postnatal day 7 (P7) rat procedure for use in mice, and later demonstrated that genetic strain strongly influences the degree of brain injury in the P7 mouse model of hypoxia-ischemia (HI). Recently, the P9 or P10 mouse brain was recognized as the developmental equivalent of a term neonatal human brain, rather than P7. Consequently, the Vannucci procedure has again been modified, and a commonly used protocol employs 10% oxygen for 50 min in C57Bl/6 mice. Strain differences have yet to be described for the P9/P10 mouse model. In order to determine if the strain differences we previously reported in the P7 mouse model are present in the P9 model, we compared 2 commonly used strains, CD1 and C57Bl/6J, in both the P7 (carotid ligation [in this case, right] followed by exposure to 8% oxygen for 30 min) and P9 (carotid ligation [in this case

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Section: Sex Differencessupporting

confidence: 49%

Strain-Related Differences in Mouse Neonatal Hypoxia-Ischemia

2018

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“…The developmental delay of physical characteristics, i.e., eye opening, ear unfolding, and incisor eruption, along with neurological reflexes, such as cliff aversion, gait, grasp, and limb placing, seem to be dependent on the severity of the injury and independent of sex (Ashwal et al, ; Huang et al, ; Nie et al, ). Motor skills in males appear to be more vulnerable to HI in the negative geotaxis test (Huang et al, ; Waddell et al, ). However, results of the righting reflex test are somehow conflicting, with some reporting that HI females (Peterson et al, ) and others that HI males are more impaired compared with control (Huang et al, ).…”

Section: Sex Differences In Behavioral Outcome and Severity Of Brain mentioning

confidence: 99%

“…Motor skills in males appear to be more vulnerable to HI in the negative geotaxis test (Huang et al, ; Waddell et al, ). However, results of the righting reflex test are somehow conflicting, with some reporting that HI females (Peterson et al, ) and others that HI males are more impaired compared with control (Huang et al, ).…”

Section: Sex Differences In Behavioral Outcome and Severity Of Brain mentioning

confidence: 99%

“…Males require more time to recognize sensory stimuli from the contralateral forepaw in the adhesive‐removal test (Peterson et al, ). In the footprints and wire‐suspension tests, HI males have shorter step length and toe distance in the contralateral limbs (Huang et al, ) and are less successful at grasping the dowel with hindlimbs and hanging on it (Waddell et al, ). With regard to balance and motor coordination deficits in the rota‐rod task, some authors have found no significant differences between males and females after the HI insult (Pimentel‐Coelho et al, ; Uluc et al, ; Gillani et al, ; Peterson et al, ).…”

Section: Sex Differences In Behavioral Outcome and Severity Of Brain mentioning

confidence: 99%

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Sex‐dependent consequences of neonatal brain hypoxia‐ischemia in the rat

Netto

Sanches

Odorcyk

et al. 2016

J of Neuroscience Research

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Neonatal hypoxia-ischemia (HI) is an important cause of neurological deficits in humans, and the Levine-Rice model of experimental HI in the rat mimics the human brain lesion and the following sensory motor deficits and cognitive disabilities. With the growing evidence that sex influences all levels of brain functions, this Mini-Review highlights studies in which sex was a controlled variable and that provided evidence of sexual dimorphism in behavioral outcome, extension of brain damage, mechanisms of lesion, and treatment efficacy in the rat neonatal HI model. It was shown that 1) females have greater memory deficits; 2) cell death is dependent mainly on caspase activation in females; 3) males are more susceptible to oxidative stress; and 4) treatments acting on distinct cell death pathways afford sex-dependent neuroprotection. These tentative conclusions, along with growing evidence from other fields of neurobiology, support the need for scientists to design their experiments considering sex as an important variable; otherwise, important knowledge will continue to be missed. It is conceivable that sex can influence the development of efficacious therapeutic tools to treat neonates suffering from brain HI. V C 2016 Wiley Periodicals, Inc.

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“…Cohort and animal studies, using hypoxia stimulus and carotid artery occlusion, have demonstrated higher vulnerability to oxygen deprivation injury in male infants born near‐ or full‐term, compared to females (Huang et al, 2016; Waddell et al, 2016). Clinically, sex differences have also been observed following traumatic brain injury, where females were more resistant to neurological deficits (Roof and Hall, 2000).…”

Section: Introductionmentioning

confidence: 99%

Behavioral, cognitive and histological changes following neonatal anoxia: Male and female rats' differences at adolescent age

Kumar

Motta-Teixeira

Takada

et al. 2018

Intl J of Devlp Neuroscience

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Neonatal anoxia induces long‐term brain injury that may underlie neurobehavioral deficits at adolescence. Neonatal anoxia, induced by exposure of 30‐hour old pups to 100% nitrogen, represents a non‐invasive and global stimulus, which simulates clinical conditions of human pre‐term babies (around 6 gestational months). Previous studies showed that neonatal anoxia induced impairments of spatial memory and altered anxiety‐like behaviors in male rats tested at adult age. This study evaluated if neonatal anoxia induces similar behavioral effects in female rats, as compared to males, by testing the animals at adolescence, and also searched for possible cell losses in hippocampal subfields. Results in the Elevated Plus Maze test showed that anoxic females spent proportionally more time within the open arms as compared to anoxic males, suggesting a less anxious‐like behavior. In the Morris Water Maze Test, latencies and path lengths of the anoxic subjects were longer as compared to control subjects, thus indicating that anoxia disrupted the cognitive functions required for spatial mapping. In addition, results showed that anoxia‐induced disruption was greater in male rats as compared to female rats. Stereological analysis revealed that anoxic male rats exhibited significant cell losses in the dorsal hippocampus dentate gyrus and CA1 subfields, but not in CA3‐2 subfield. Similar results were observed in the ventral hippocampus, but now with cell loss in the male CA3‐2 subfield. There were also significant cell loss differences of anoxic male rats as compared to anoxic female rats. In conclusion, neonatal anoxia induces deleterious and long lasting behavioral and cognitive disruptions, and these effects were stronger in male rats as compared to female rats. These changes are congruent with the pattern of cell losses observed in hippocampal subfields. Together, these results emphasize the relevance of scientific research, aiming at clinical strategies and treatments, consider the sex differential patterns of response to neonatal injury.

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Sex differences in brain MRI abnormalities and neurodevelopmental outcomes in a rat model of neonatal hypoxia-ischemia

Cited by 29 publications

References 58 publications

Strain-Related Differences in Mouse Neonatal Hypoxia-Ischemia

Strain-Related Differences in Mouse Neonatal Hypoxia-Ischemia

Sex‐dependent consequences of neonatal brain hypoxia‐ischemia in the rat

Behavioral, cognitive and histological changes following neonatal anoxia: Male and female rats' differences at adolescent age

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