scholarly journals Effects of therapeutic hypothermia on white matter injury from murine neonatal hypoxia–ischemia

2017 ◽  
Vol 82 (3) ◽  
pp. 518-526 ◽  
Author(s):  
Elliot Koo ◽  
R Ann Sheldon ◽  
Byong Sop Lee ◽  
Zinaida S Vexler ◽  
Donna M Ferriero
Keyword(s):  
White Matter ◽  
Therapeutic Hypothermia ◽  
White Matter Injury ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

scholarly journals Histamine H2 receptor negatively regulates oligodendrocyte differentiation in neonatal hypoxic-ischemic white matter injury

2020 ◽  
Vol 218 (1) ◽  
Author(s):  
Lei Jiang ◽  
Li Cheng ◽  
Han Chen ◽  
Haibin Dai ◽  
Dadao An ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Injury ◽  
Mature Stage ◽  
Oligodendrocyte Differentiation ◽  
Cell Stage ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

Neonatal hypoxic-ischemic encephalopathy (HIE) with the pathological characteristic of white matter injury often leads to lifelong cognitive and neurobehavioral dysfunction, but relevant therapies to promote remyelination are still unavailable. We found that histamine H2 receptor (H2R) negatively regulated the oligodendrocyte differentiation rate without affecting the oligodendrocytes at the oligodendrocyte precursor cell stage or mature stage following oxygen-glucose deprivation in vitro. Notably, selective deletion of the H2R gene (Hrh2) in differentiating oligodendrocytes (Hrh2fl/fl;CNPase-Cre) improved their differentiation, remyelination, and functional recovery following neonatal hypoxia-ischemia in mice. The regulation of oligodendrocyte differentiation by H2R is mediated by binding with Axin2, which leads to up-regulation of the Wnt/β-catenin signaling pathway. Furthermore, H2R antagonists also promoted oligodendrocyte differentiation and remyelination and the recovery of cognition and motor functions following neonatal hypoxia-ischemia. Thus, histamine H2R in oligodendrocytes could serve as a novel and effective therapeutic target for the retard of oligodendrocyte differentiation and remyelination following neonatal hypoxia-ischemia. The H2R antagonists may have potential therapeutic value for neonatal HIE.

scholarly journals Correlation Between White Matter Injury Identified by Neonatal Diffusion Tensor Imaging and Neurodevelopmental Outcomes Following Term Neonatal Asphyxia and Therapeutic Hypothermia: An Exploratory Pilot Study

2019 ◽  
Vol 34 (10) ◽  
pp. 556-566 ◽  
Author(s):  
Gwendolyn J. Gerner ◽  
Eric I. Newman ◽  
V. Joanna Burton ◽  
Brenton Roman ◽  
Elizabeth A. Cristofalo ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Pilot Study ◽  
Therapeutic Hypothermia ◽  
Diffusion Tensor ◽  
White Matter Injury ◽  
Hypoxic Ischemic Encephalopathy ◽  
Group Differences ◽  
Neurodevelopmental Outcomes ◽  
Ischemic Encephalopathy

Aim: Hypoxic-ischemic encephalopathy is associated with damage to deep gray matter; however, white matter involvement has become recognized. This study explored differences between patients and clinical controls on diffusion tensor imaging, and relationships between diffusion tensor imaging and neurodevelopmental outcomes. Method: Diffusion tensor imaging was obtained for 31 neonates after hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and 10 clinical controls. A subgroup of patients with hypoxic-ischemic encephalopathy (n = 14) had neurodevelopmental outcomes correlated with diffusion tensor imaging scalars. Results: Group differences in diffusion tensor imaging scalars were observed in the putamen, anterior and posterior centrum semiovale, and the splenium of the corpus callosum. Differences in these regions of interest were correlated with neurodevelopmental outcomes between ages 20 and 32 months. Conclusion: Therapeutic hypothermia may not be a complete intervention for hypoxic-ischemic encephalopathy, as neonatal white matter changes may continue to be evident, but further research is warranted. Patterns of white matter change on neonatal diffusion tensor imaging correlated with neurodevelopmental outcomes in this exploratory pilot study.

scholarly journals Calbindin-1 Expression in the Hippocampus following Neonatal Hypoxia-Ischemia and Therapeutic Hypothermia and Deficits in Spatial Memory

2018 ◽  
Vol 40 (5-6) ◽  
pp. 508-522 ◽  
Author(s):  
Janasha Goffigan-Holmes ◽  
Dafne Sanabria ◽  
Johana Diaz ◽  
Debra Flock ◽  
Raul Chavez-Valdez
Keyword(s):  
Therapeutic Hypothermia ◽  
Neurodegenerative Disorders ◽  
Memory Impairment ◽  
Memory Deficits ◽  
Nissl Staining ◽  
Memory Impairments ◽  
Neonatal Hypoxia ◽  
Y Maze ◽  
Hypoxia Ischemia ◽  
With Memory

Hippocampal injury following neonatal hypoxia-ischemia (HI) leads to memory impairments despite therapeutic hypothermia (TH). In the hippocampus, the expression of calbindin-1 (Calb1), a Ca2+-buffering protein, increases during postnatal development and decreases with aging and neurodegenerative disorders. Since persistent Ca2+ dysregulation after HI may lead to ongoing injury, persistent changes in hippocampal expression of Calb1 may contribute to memory impairments after neonatal HI. We hypothesized that, despite TH, neonatal HI persistently decreases Calb1 expression in the hippocampus, a change associated with memory deficits in the mouse. We induced cerebral HI in C57BL6 mice at postnatal day 10 (P10) with right carotid ligation and 45 min of hypoxia (FiO2 = 0.08), followed by normothermia (36°C, NT) or TH (31°C) for 4 h with anesthesia-shams as controls. Nissl staining and glial fibrillary acidic protein (GFAP) immunohistochemistry (IHC) were used to grade brain injury and astrogliosis at P11, P18, and P40 prior to the assessment of Calb1 expression by IHC. The subset of mice followed to P40 also performed a memory behavior task (Y-maze) at P22–P26. Nonparametric statistics stratified by sex were applied. In both anterior and posterior coronal brain sections, hippocampal Calb1 expression doubled between P11 and P40 due to an increase in the cornus ammonis (CA) field (Kruskal-Wallis [KW] p < 0.001) and not the dentate gyrus (DG). Neonatal HI produced delayed (P18) and late (P40) deficits in the expression of Calb1 exclusively in the CA field (KW p = 0.02) in posterior brain sections. TH did not attenuate Calb1 deficits after HI. Thirty days after HI injury (at P40), GFAP scores in the hippocampus (p < 0.001, r = –0.47) and CA field (p < 0.001, r = –0.39) of posterior brain sections inversely correlated with their respective Calb1 expression. Both sexes demonstrated deficits in Y-maze testing, including approximately 40% lower spontaneous alterations performance and twice as much total impairment compared to sham mice (KW p < 0.001), but it was only in females that these deficits correlated with the Calb1 expression in the hippocampal CA field (p < 0.05) of the posterior sections. Hippocampal atrophy after neonatal HI also correlated with worse deficits in Y-maze testing, but it did not predict Calb1 deficits. Neonatal HI produces a long-lasting Calb1 deficit in the hippocampal CA field during development, which is not mitigated by TH. Late Calb1 deficit after HI may be the result of persistent astrogliosis and can lead to memory impairment, particularly in female mice.

scholarly journals Synaptic Injury in the Thalamus Accompanies White Matter Injury in Hypoxia/Ischemia-Mediated Brain Injury in Neonatal Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Na Liu ◽  
Xin Tong ◽  
Wanjie Huang ◽  
Jianhua Fu ◽  
Xindong Xue
Keyword(s):  
White Matter ◽  
White Matter Injury ◽  
Neonatal Rat ◽  
Morris Water Maze Test ◽  
Neonatal Rats ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Compensatory Response ◽  
Significant Difference ◽  
Hypoxia Ischemia

The broad spectrum of disabilities caused by white matter injury (WMI) cannot be explained simply by hypomyelination. Synaptic injury in the thalamus may be related to disabilities in WMI survivors. Neuronal injury in the thalamus has been found most commonly in autopsy cases of preterm WMI. We hypothesized that hypoxia/ischemia (HI) in neonatal rats results in synaptic abnormalities in the thalamus that contribute to disabilities in WMI survivors. We examined changes in synapses in a neonatal rat model of HI-induced WMI. Right common carotid artery ligation and hypoxia (8% oxygen for 2.5 hours (h)) were performed in three-day-old Sprague-Dawley rats. We found HI rats performed worse in the Morris water maze test than sham rats, suggesting long-term cognition impairment after HI injury. A loss of synapses in the thalamus accompanied by hypomyelination and oligodendrocytes (OLs) reduction was observed. At the ultrastructural level, reductions in active zone (AZ) length and postsynaptic density (PSD) thickness were detected at 2 weeks after HI exposure. Furthermore, increased expression of synaptophysin and PSD-95 in both groups was observed from 3 days (d) to 21 d after hypoxic/ischemic (HI) injury. PSD-95 expression was significantly lower in HI rats than in sham rats from 14 d to 21 d after HI injury, and synaptophysin expression was significantly lower in HI rats from 7 d to 14 d after HI injury. However, no significant difference in synaptophysin expression was observed between HI rats and sham rats at 21 d after HI injury. The results demonstrated synaptic abnormalities in the thalamus accompanied by hypomyelination in WMI in response to HI exposure, which may contribute to the diverse neurological defects observed in WMI patients. Although synaptic reorganization occurred as a compensatory response to HI injury, the impairments in synaptic transmission were not reversed.

scholarly journals Longitudinal diffusion tensor and manganese-enhanced MRI detect delayed cerebral gray and white matter injury after hypoxia–ischemia and hyperoxia

2012 ◽  
Vol 73 (2) ◽  
pp. 171-179 ◽  
Author(s):  
Tora Sund Morken ◽  
Marius Widerøe ◽  
Christina Vogt ◽  
Stian Lydersen ◽  
Marianne Havnes ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
White Matter Injury ◽  
Longitudinal Diffusion ◽  
Enhanced Mri ◽  
Hypoxia Ischemia ◽  
Manganese Enhanced Mri
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