Diffusion kurtosis imaging and pathological comparison of early hypoxic–ischemic brain damage in newborn piglets

Abstract To investigate the application value of magnetic resonance diffusion kurtosis imaging (DKI) in hypoxic–ischemic brain damage (HIBD) in newborn piglets and to compare imaging and pathological results. Of 36 piglets investigated, 18 were in the experimental group and 18 in the control group. The HIBD model was established in newborn piglets by ligating the bilateral common carotid arteries and placing them into hypoxic chamber. All piglets underwent conventional MRI and DKI scans at 3, 6, 9, 12, 16, and 24 h postoperatively. Mean kurtosis (MK) and mean diffusivity (MD) maps were constructed. Then, the lesions were examined using light and electron microscopy and compared with DKI images. The MD value of the lesion area gradually decreased and the MK value gradually increased in the experimental group with time. The lesion areas gradually expanded with time; MK lesions were smaller than MD lesions. Light microscopy revealed neuronal swelling in the MK- and MD-matched and mismatched regions. Electron microscopy demonstrated obvious mitochondrial swelling and autophagosomes in the MK- and MD-matched region but normal mitochondrial morphology or mild swelling in the mismatched region. DKI can accurately evaluate early ischemic–hypoxic brain injury in newborn piglets.

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HMBG1 Mediates Ischemia—Reperfusion Injury by TRIF-Adaptor Independent Toll-Like Receptor 4 Signaling

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.129 ◽

2010 ◽

Vol 31 (2) ◽

pp. 593-605 ◽

Cited By ~ 97

Author(s):

Qing-Wu Yang ◽

Feng-Lin Lu ◽

Yu Zhou ◽

Lin Wang ◽

Qi Zhong ◽

...

Keyword(s):

Reperfusion Injury ◽

Brain Damage ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Control Group ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Hmgb1 Level ◽

Ischemic Brain Damage ◽

Ischemic Brain

High-mobility group protein box-1 (HMGB1) has recently been recognized as a novel candidate in a specific upstream pathway promoting inflammation after brain ischemia. However, its downstream pathway and underlying mechanism have yet to be elucidated. The HMGB1 level in the acute cerebral infarct (ACI) group was significantly increased compared with that of control group, and correlated with the severity of neurologic impairment of ACI patients. Further, recombinant human HMGB1 (rhHMGB1) had no effect on microglia derived from mice lacking the Toll-like receptor 4 (TLR4−/–). Intracerebroventricular injection of rhHMGB1 in TLR4+/+ mice cause significantly more injury after cerebral ischemia–reperfusion than control group. But, TLR4−/– mice administered with rhHMGB1 showed moderate impairment after ischemia–reperfusion than TLR4+/+ mice. To determine the potential downstream signaling of HMGB1/TLR4 in cerebral ischemic injury, we used the ischemic–reperfusion model with Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-β knockout mice (TRIF−/–) and evaluated the activity and expression of TRIF pathway-related kinases. The results suggest that the TRIF pathway is not likely to be involved in TLR4-mediated ischemia brain injury. Finally, we found that TLR4 expressed by immigrant macrophages was involved in the development of ischemic brain damage. These results suggest that HMBG1 mediates ischemia–reperfusion injury by TRIF-adaptor independent Toll-like receptor 4 signaling. The TLR4 expressed by immigrant macrophages may be involved in the development of ischemic brain damage.

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Cannabidiol reduces lung injury induced by hypoxic–ischemic brain damage in newborn piglets

Pediatric Research ◽

10.1038/pr.2017.104 ◽

2017 ◽

Vol 82 (1) ◽

pp. 79-86 ◽

Cited By ~ 5

Author(s):

Luis Arruza ◽

Maria Ruth Pazos ◽

Nagat Mohammed ◽

Natalia Escribano ◽

Hector Lafuente ◽

...

Keyword(s):

Lung Injury ◽

Brain Damage ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Newborn Piglets

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Hypoxic–ischemic brain damage induces distant inflammatory lung injury in newborn piglets

Pediatric Research ◽

10.1038/pr.2015.87 ◽

2015 ◽

Vol 79 (3) ◽

pp. 401-408 ◽

Cited By ~ 6

Author(s):

Luis Arruza ◽

M. Ruth Pazos ◽

Nagat Mohammed ◽

Natalia Escribano ◽

Hector Lafuente ◽

...

Keyword(s):

Lung Injury ◽

Brain Damage ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Newborn Piglets

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Comparative evaluation of pre- and postoperative administration of citicoline: clinical outcomes and the volume of ischemic brain damage after meningioma removal

Sechenov Medical Journal ◽

10.47093/22187332.2019.4.12-20 ◽

2019 ◽

Vol 10 (4) ◽

pp. 12-20

Author(s):

G. Z. Sufianova ◽

A. G. Shapkin ◽

A. A. Sufianov ◽

M. S. Khlеstkina ◽

R. A. Sufianov ◽

...

Keyword(s):

Skull Base ◽

Clinical Outcomes ◽

Brain Damage ◽

Postoperative Period ◽

Randomized Clinical Trials ◽

Postoperative Mortality ◽

Control Group ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

The Third

In the experimental model of cerebral ischemia, citicoline has shown greater eﬀectiveness with its preventive use compared with therapeutic one.Aim. To study the main clinical outcomes and the dynamics of morphometric indicators of ischemic brain damage according to computed tomography (CT) data in patients with meningiomas of the skull base in the postoperative period against the background of prophylactic and therapeutic administration of citicoline.Materials and methods. The study included 53 patients aged 40 to 69 years with the skull base meningiomas. The ﬁrst (control) group (n=17) and the third group, in which citicoline was administered in the postoperative period for 7–21 days at a dose of 1000 mg 2 times a day intravenously (n=25), were formed retrospectively. The second group (n=11), in which citicoline was administered prophylactically 1.5–2.5 hours before surgery at a dose of 2000 mg intravenously, was formed prospectively. We evaluated the main clinical outcomes and CT morphometry data.Results. The average time spent in the intensive care unit was minimal in the second group: 9.6±3.2 days vs 17.6±3.7 days in the control (p=0.049). Postoperative mortality was 24% in the control group, 9% in the second group, and 20% in the third group. The survival time in the ﬁrst group was less than 21 days, over 21 days in the second and third groups. The groups did not diﬀer in neurological outcomes and overall in-hospital stay. The average volume of ischemic brain damage on the ﬁrst day after surgery in the second group was less than in the control group, and amounted to 111.7±15.2 cm3 against 151.3±17.1 cm3, respectively (p=0.044).Conclusion. The prophylactic administration of citicoline before a tumor removal operation may have eﬀective potential for reducing the severity and prevalence of ischemic cerebral edema. Further randomized clinical trials are needed.

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Evaluation of Altered Glutamatergic Activity in a Piglet Model of Hypoxic-Ischemic Brain Damage Using 1H-MRS

Disease Markers ◽

10.1155/2020/8850816 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yuxue Dang ◽

Xiaoming Wang

Keyword(s):

Basal Ganglia ◽

Brain Damage ◽

Protein Level ◽

Excitatory Amino Acid ◽

Oxygen Mixture ◽

Control Group ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Protein Levels ◽

Bilateral Carotid

Background and Objective. The excitotoxicity of glutamate (Glu) is a major risk factor for neonatal hypoxic-ischemic brain damage (HIBD). The role of excitatory amino acid transporter 2 (EAAT2) and the α-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid receptor (AMPAR) subunit GluR2 in mediating the Glu excitotoxicity has always been the hotspot. This study was aimed at investigating the early changes of glutamate metabolism in the basal ganglia following hypoxia-ischemia (HI) in a neonatal piglet model using 1H-MRS. Methods. Twenty-five newborn piglets were selected and then randomly assigned to the control group (n=5) and the model group (n=20) subjected to HI. HI was induced by blocking bilateral carotid blood flow under simultaneous inhalation of a 6% oxygen mixture. 1H-MRS data were acquired from the basal ganglia at the following time points after HI: 6, 12, 24, and 72 h. Changes in protein levels of EAAT2 and GluR2 were determined by immunohistochemical analysis. Correlations among metabolite concentrations, metabolite ratios, and the protein levels of EAAT2 and GluR2 were investigated. Results. The Glu level sharply increased after HI, reached a transient low level of depletion that approached the normal level in the control group, and subsequently increased again. Negative correlations were found between concentrations of Glu and EAAT2 protein levels (Rs=−0.662, P<0.001) and between the Glu/creatine (Cr) ratio and EAAT2 protein level (Rs=−0.664, P<0.001). Moreover, changes in GluR2 protein level were significantly and negatively correlated with those in Glu level (the absolute Glu concentration, Rs=−0.797, P<0.001; Glu/Cr, Rs=−0.567, P=0.003). Conclusions. Changes in Glu level measured by 1H-MRS were inversely correlated with those in EAAT2 and GluR2 protein levels following HI, and the results demonstrated that 1H-MRS can reflect the early changes of glutamatergic activity in vivo.

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