Sex differences in the benefits of rehabilitative training during adolescence following neonatal hypoxia–ischemia in rats

Tsuji, Masahiro; Aoo, Naoya; Harada, Kazuhiro; Sakamoto, Yuya; Akitake, Yoshiharu; Irie, Keiichi; Mishima, Kenichi; Ikeda, Tomoaki; Fujiwara, Michihiro

doi:10.1016/j.expneurol.2010.09.002

Cited by 28 publications

(25 citation statements)

References 61 publications

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“…Our results confirm more global deficits in male rats after HI. This pattern has been reported by other groups [28, 31, 34, 62]. An elegant and thourough study has determined that males subjected to HI suffer rapid auditory processing deficits, while females remain unaffected [34].…”

Section: Discussionsupporting

confidence: 74%

Neuroprotective Effects of Acetyl-<smlcap>L</smlcap>-Carnitine on Neonatal Hypoxia Ischemia-Induced Brain Injury in Rats

Tang

Lü

et al. 2016

Dev Neurosci

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Perinatal hypoxia ischemia (HI) is a significant cause of brain injury in surviving infants. Although hypothermia improves outcomes in some infants, additional therapies are needed since about 40% of infants still have a poor outcome. Acetyl-L-carnitine (ALCAR), an acetylated derivative of L-carnitine, protected against early changes in brain metabolites and mitochondrial function after HI on postnatal day (PND) 7 in a rat pup model of near-term HI injury. However, its efficacy in long-term structural and functional outcomes remains unexplored. We determined the efficacy of ALCAR therapy administered to rat pups after HI at PND 7, using both longitudinal in vivo magnetic resonance imaging and behavioral tests, in male and female rats. HI led to sex-specific behavioral impairment, with males exhibiting more global functional deficits than females. Interestingly, HI reduced the volume of the contralateral hemisphere in males only, suggesting that the brain injury is more diffuse in males than in females. Treatment with ALCAR improved both morphological and functional outcomes in both male and female rats. These results suggest that ALCAR may be a potential therapy for clinical use since the treatment attenuated the moderate injury produced under the experimental conditions used and improved the functional outcome in preclinical studies.

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Section: Discussionsupporting

confidence: 74%

Neuroprotective Effects of Acetyl-<smlcap>L</smlcap>-Carnitine on Neonatal Hypoxia Ischemia-Induced Brain Injury in Rats

Tang

Lü

et al. 2016

Dev Neurosci

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“…A morphological evaluation of the brain injury was performed as previously described [15,23,24] . Animals were perfusion-fixed intracardially with 4% paraformaldehyde 2 and 7 weeks after insult.…”

Section: Morphological Brain Injurymentioning

confidence: 99%

Evaluations of Intravenous Administration of CD34<sup>+</sup> Human Umbilical Cord Blood Cells in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy

Ohshima

Taguchi²,

Sato³

et al. 2016

Dev Neurosci

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Several cell therapies have been explored as novel therapeutic strategies for neonatal encephalopathy because the benefits of current treatments are limited. We previously reported that intravenous administration of human umbilical cord blood (hUCB) CD34⁺ cells (hematopoietic stem cells/endothelial progenitor cells) at 48 h after insult exerts therapeutic effects in neonatal mice with stroke, i.e., permanent middle cerebral artery occlusion. Although neonatal stroke and hypoxic-ischemic encephalopathy (HIE) are grouped under the term “neonatal encephalopathy,” their pathogenesis differs. However, little is known about the differences in the effects of the same treatment between these 2 diseases. In this study, we investigated whether the same treatment protocol exerts therapeutic effects in neonatal mice with HIE. The treatment significantly ameliorated the decreased cerebral blood flow in the ischemic penumbra. Although the cylinder and rotarod tests showed a trend of amelioration of behavioral impairments from the treatment, these were not statistically significant. Morphological brain injuries were not altered by treatment. The cell administration did not cause any adverse effects apart from hyperactivity in the open-field test. Some of these findings are consistent with the results obtained in our previous study using a stroke model, but others are not. This study suggests that the treatment protocol needs to be optimized for each pathological condition.

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“…Males have worse outcome after traumatic brain injury (TBI) [10] and cardiac arrest [11] compared with females. Rehabilitative training improved functional outcome and infarct size in female but not male immature rats after hypoxia ischemia [12]. Many neurodegenerative diseases also exhibit sexbased disparity in terms of both incidence and response to treatment.…”

Section: Introductionmentioning

confidence: 93%

Unmasking Sex-Based Disparity in Neuronal Metabolism

Manole

Tehranian-DePasquale²,

Du³

et al. 2011

CPD

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Both classic and emerging literature point to sex-based disparity in neuronal metabolism. While detectable under baseline conditions, this phenomenon appears to be exaggerated or sometimes unmasked in neurons by cellular stress. A complex sex-dependent response to nutrient deprivation, excitotoxicity, oxidative/nitrositive stress, oxygen-glucose deprivation, and chemical toxicity has been observed in neurons in vitro, as well as after various insults including ischemic or traumatic brain injury in vivo. Importantly, sex-based disparity in response to diverse therapeutics has been seen in neurons in culture, contemporary animal models of brain injury, and in human disease. These have clear implications for pharmacological design of therapeutics targeting central nervous system diseases involving both males and females, and preclinical testing of promising agents.

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Sex differences in the benefits of rehabilitative training during adolescence following neonatal hypoxia–ischemia in rats

Cited by 28 publications

References 61 publications

Neuroprotective Effects of Acetyl-<smlcap>L</smlcap>-Carnitine on Neonatal Hypoxia Ischemia-Induced Brain Injury in Rats

Neuroprotective Effects of Acetyl-<smlcap>L</smlcap>-Carnitine on Neonatal Hypoxia Ischemia-Induced Brain Injury in Rats

Evaluations of Intravenous Administration of CD34<sup>+</sup> Human Umbilical Cord Blood Cells in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy

Unmasking Sex-Based Disparity in Neuronal Metabolism

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