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Intrauterine growth restriction and neonatal hypoxic ischemic brain injury causes sex‐specific long‐term neurobehavioral abnormalities in rats
Author(s) -
Narang Radhika,
Carter Kathleen,
Muncie Colin,
Pang Yi,
Fan LirWan W.,
Feng Yangzheng,
Ojeda Norma B.,
Bhatt Abhay J.
Publication year - 2019
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24389
Subject(s) - hypoxia (environmental) , intrauterine growth restriction , medicine , ischemic injury , physiology , cardiology , neuroscience , ischemia , anesthesia , psychology , biology , pregnancy , fetus , chemistry , genetics , organic chemistry , oxygen
There is a lack of knowledge of factors preventing an adequate response to moderate hypothermia after hypoxic ischemic (HI) brain injury. We hypothesized that growth restriction from reduced intrauterine perfusion would predispose neonatal rats to have a worse outcome with HI brain injury. IUGR was induced by placental insufficiency in dams at 14 days of gestation. HI was induced at postnatal day (P) 10 by permanent right carotid artery ligation followed by 90 min of hypoxia (8% oxygen). Tests for early brain injury and neurobehavioral outcomes were subsequently done. All statistical analysis was done using Two‐way ANOVA; post hoc Holm‐Sidak test. HI in control and IUGR groups decreased the success rate of the contralateral vibrissa‐elicited forelimb test, increased response latency in movement initiation test and increased the time to finish elevated beam walk test at P40 and P60. IUGR augmented HI‐induced abnormality in vibrissa‐elicited forelimb test at P40 but showed higher success rate when compared to HI only group at P60. IUGR’s negative effect on HI‐induced changes on the elevated beam walk test was sex‐specific and exaggerated in P60 males. Increased TUNEL positive cells in the cortex were noted at 72 h after in HI in control but not in IUGR groups. In conclusion, the consequences of IUGR on subsequent neonatal HI varied based on age, sex and outcomes examined, and overall, male sex and IUGR had worse effects on the long‐term neurobehavioral outcomes following HI.

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