Share:
Share this content in WeChat
X
Original Article
Study of conventional MRI combined with SWI on brain damage after asphyxia in neonatal rats and compared with pathological
XIE Beichen  YAN Ruifang  REN Jipeng  NIU Jin  LI Haiming  DU Chaoyang 

Cite this article as: XIE B C, YAN R F, REN J P, et al. Study of conventional MRI combined with SWI on brain damage after asphyxia in neonatal rats and compared with pathological[J]. Chin J Magn Reson Imaging, 2023, 14(7): 108-114. DOI:10.12015/issn.1674-8034.2023.07.019.


[Abstract] Objective To investigate the pathological types of hypoxic brain injury in neonatal rats after asphyxia by conventional magnetic resonance imaging (MRI) and susceptibility-weighted imaging (SWI), and to explore the effects of hypoxia on the cortex and hippocampus.Materials and Methods Neonatal 7-day-old rats were randomly divided into asphyxiation and control groups. Pups in the asphyxiation group were placed in a closed chamber for a hypoxia with the oxygen concentration with 1% (5 min)-reoxygenation with the oxygen concentration of 21% (3 min) cycle for a cumulative hypoxia time of 30 min; control rats were placed in the same chamber with air for the same time. Behavioral changes and changes in general conditions of baby rats during and after hypoxia were observed during asphyxia. Abnormal behavioral observations were made and recorded at 1 d, 3 d and 7 d after hypoxia. T1WI, T2WI and SWI sequences were performed at 1 d, 3 d and 7 d after modelling. Hematoxylin-Eosin staining was performed according to the site of abnormal MRI signal to observe the type of pathological injury in the abnormal signal area. Neuronal survival in the cortical, dentate grrus (DG), CA1 (corn ammonis 1) and CA3 (corn ammonis 3) regions of the hippocampus of young rats was observed by Nissl staining; the expression of apoptosis-related protein Caspase-3 was detected by immunohistochemical staining.Results Seizures were observed in pups at 1 d, 3 d and 7 d after hypoxia. MRI and SWI showed types of brain injury including enlarged ventricles, foci of cerebral softening, intraventricular and parenchymal hemorrhage and microvascular dilatation. Nissl staining showed a decrease in neurons in the cortical and hippocampal DG regions at 1 d, 3 d and 7 d after hypoxia compared to the control group (P<0.05), and a decrease in neurons in the CA3 region at 7 d after hypoxia (P<0.05). Immunohistochemical staining showed that the expression of Caspase-3 in the DG region of the hippocampus was higher than that of the control group at 1 d, 3 d and 7 d after hypoxia (P<0.05), and the expression in the cortex was higher than that of the control group at 3 d and 7 d after hypoxia (P<0.05); the expression in the CA1 and CA3 regions of the hippocampus was higher than that of the control group at 7 d after hypoxia (P<0.05).Conclusions MRI and SWI show that brain damage can be present early in acute intermittent hypoxia and that hypoxic brain damage can lead to seizures. This suggests that MRI and SWI should be used as routine clinical investigations in children with a history of asphyxia and suspected brain injury, and that early clinical intervention should be undertaken.
[Keywords] hypoxia;brain injury;seizure;neonatal rats;magnetic sensitivity-wighted imaging;magnetic resonance imaging

XIE Beichen1   YAN Ruifang1*   REN Jipeng1   NIU Jin1, 2   LI Haiming2   DU Chaoyang2  

1 Department of Magnetic Resonance, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China

2 Henan Provincial Key Laboratory of Neurorepair, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China

Corresponding author: Yan RF, E-mail: yrf718@163.com

Conflicts of interest   None.

Received  2023-02-10
Accepted  2023-06-28
DOI: 10.12015/issn.1674-8034.2023.07.019
Cite this article as: XIE B C, YAN R F, REN J P, et al. Study of conventional MRI combined with SWI on brain damage after asphyxia in neonatal rats and compared with pathological[J]. Chin J Magn Reson Imaging, 2023, 14(7): 108-114. DOI:10.12015/issn.1674-8034.2023.07.019.

[1]
MOSHIRO R, MDOE P, PERLMAN J M. A global view of neonatal asphyxia and resuscitation[J/OL]. Front Pediatr, 2019, 7: 489 [2022-05-18]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902004/pdf/fped-07-00489.pdf. DOI: 10.3389/fped.2019.00489.
[2]
WOOD S, CRAWFORD S, HICKS M, et al. Hospital-related, maternal, and fetal risk factors for neonatal asphyxia and moderate or severe hypoxic-ischemic encephalopathy: a retrospective cohort study[J]. J Matern Fetal Neonatal Med, 2021, 34(9): 1448-1453. DOI: 10.1080/14767058.2019.1638901.
[3]
GRECO P, NENCINI G, PIVA I, et al. Pathophysiology of hypoxic-ischemic encephalopathy: a review of the past and a view on the future[J]. Acta Neurol Belg, 2020, 120(2): 277-288. DOI: 10.1007/s13760-020-01308-3.
[4]
ZHANG S, LI B B, ZHANG X L, et al. Birth asphyxia is associated with increased risk of cerebral palsy: a meta-analysis[J/OL]. Front Neurol, 2020, 11: 704 [2022-05-18]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902004/pdf/fped-07-00489.pdf. DOI: 10.3389/fneur.2020.00704.
[5]
YAGER J Y. Animal models of hypoxic-ischemic brain damage in the newborn[J]. Semin Pediatr Neurol, 2004, 11(1): 31-46. DOI: 10.1016/j.spen.2004.01.006.
[6]
TORRES-CUEVAS I, CORRAL-DEBRINSKI M, GRESSENS P. Brain oxidative damage in murine models of neonatal hypoxia/ischemia and reoxygenation[J/OL]. Free Radic Biol Med, 2019, 142: 3-15 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/31226400/. DOI: 10.1016/j.freeradbiomed.2019.06.011.
[7]
TUCKER L D, LU Y J, DONG Y, et al. Photobiomodulation therapy attenuates hypoxic-ischemic injury in a neonatal rat model[J]. J Mol Neurosci, 2018, 65(4): 514-526. DOI: 10.1007/s12031-018-1121-3.
[8]
ZHANG Z H, LIU W H, SHEN M L, et al. Protective effect of GM1 attenuates Hippocampus and cortex apoptosis after ketamine exposure in neonatal rat via PI3K/AKT/GSK3β pathway[J]. Mol Neurobiol, 2021, 58(7): 3471-3483. DOI: 10.1007/s12035-021-02346-5.
[9]
TAKADA S H, SAMPAIO C A, ALLEMANDI W, et al. A modified rat model of neonatal anoxia: development and evaluation by pulseoximetry, arterial gasometry and Fos immunoreactivity[J]. J Neurosci Methods, 2011, 198(1): 62-69. DOI: 10.1016/j.jneumeth.2011.03.009.
[10]
ALA-KURIKKA T, POSPELOV A, SUMMANEN M, et al. A physiologically validated rat model of term birth asphyxia with seizure generation after, not during, brain hypoxia[J]. Epilepsia, 2021, 62(4): 908-919. DOI: 10.1111/epi.16790.
[11]
CHEN S J, LIU X L, MEI Y J, et al. Early identification of neonatal mild hypoxic-ischemic encephalopathy by amide proton transfer magnetic resonance imaging: a pilot study[J/OL]. Eur J Radiol, 2019, 119: 108620 [2022-05-18]. https://www.ejradiology.com/article/S0720-048X(19)30263-3/fulltext. DOI: 10.1016/j.ejrad.2019.07.021.
[12]
ROUMES H, DUMONT U, SANCHEZ S, et al. Neuroprotective role of lactate in rat neonatal hypoxia-ischemia[J]. J Cereb Blood Flow Metab, 2021, 41(2): 342-358. DOI: 10.1177/0271678X20908355.
[13]
VAN DEN BROECK C, HIMPENS E, VANHAESEBROUCK P, et al. Influence of gestational age on the type of brain injury and neuromotor outcome in high-risk neonates[J]. Eur J Pediatr, 2008, 167(9): 1005-1009. DOI: 10.1007/s00431-007-0629-2.
[14]
KIM H G, CHOI J W, HAN M R, et al. Texture analysis of deep medullary veins on susceptibility-weighted imaging in infants: evaluating developmental and ischemic changes[J]. Eur Radiol, 2020, 30(5): 2594-2603. DOI: 10.1007/s00330-019-06618-6.
[15]
JOHNE M, RÖMERMANN K, HAMPEL P, et al. Phenobarbital and midazolam suppress neonatal seizures in a noninvasive rat model of birth asphyxia, whereas bumetanide is ineffective[J]. Epilepsia, 2021, 62(4): 920-934. DOI: 10.1111/epi.16778.
[16]
SEMPLE B D, BLOMGREN K, GIMLIN K, et al. Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species[J]. Prog Neurobiol, 2013, 106/107(1): 1-16. DOI: 10.1016/j.pneurobio.2013.04.001.
[17]
BERNIS M E, ZWEYER M, MAES E, et al. Neutrophil extracellular traps release following hypoxic-ischemic brain injury in newborn rats treated with therapeutic hypothermia[J/OL]. Int J Mol Sci, 2023, 24(4): 3598 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/36835009/. DOI: 10.3390/ijms24043598.
[18]
TONNI G, LEONCINI S, SIGNORINI C, et al. Pathology of perinatal brain damage: background and oxidative stress markers[J]. Arch Gynecol Obstet, 2014, 290(1): 13-20. DOI: 10.1007/s00404-014-3208-6.
[19]
NOVAK C M, OZEN M, BURD I. Perinatal brain injury: mechanisms, prevention, and outcomes[J]. Clin Perinatol, 2018, 45(2): 357-375. DOI: 10.1016/j.clp.2018.01.015.
[20]
KUMAR A J, MOTTA-TEIXEIRA L C, TAKADA S H, et al. Behavioral, cognitive and histological changes following neonatal anoxia: male and female rats' differences at adolescent age[J/OL]. Int J Dev Neurosci, 2019, 73: 50-58 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/30562544/. DOI: 10.1016/j.ijdevneu.2018.12.002.
[21]
TAKADA S H, DOS SANTOS HAEMMERLE C A, MOTTA-TEIXEIRA L C, et al. Neonatal anoxia in rats: Hippocampal cellular and subcellular changes related to cell death and spatial memory[J/OL]. Neuroscience, 2015, 284: 247-259 [2022-05-18]. https://www.ibroneuroscience.org/article/S0306-4522(14)00824-0/fulltext. DOI: 10.1016/j.neuroscience.2014.08.054.
[22]
BEROSKE L, VAN DEN WYNGAERT T, STROOBANTS S, et al. Molecular imaging of apoptosis: the case of caspase-3 radiotracers[J/OL]. Int J Mol Sci, 2021, 22(8): 3948 [2022-05-18]. https://www.mdpi.com/1422-0067/22/8/3948. DOI: 10.3390/ijms22083948.
[23]
STECKLER T, RISBROUGH V. Pharmacological treatment of PTSD - established and new approaches[J]. Neuropharmacology, 2012, 62(2): 617-627. DOI: 10.1016/j.neuropharm.2011.06.012.
[24]
ZANELLI S, GOODKIN H P, KOWALSKI S, et al. Impact of transient acute hypoxia on the developing mouse EEG[J/OL]. Neurobiol Dis, 2014, 68: 37-46 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/24636798/. DOI: 10.1016/j.nbd.2014.03.005.
[25]
REMZSŐ G, NÉMETH J, VARGA V, et al. Brain interstitial pH changes in the subacute phase of hypoxic-ischemic encephalopathy in newborn pigs[J/OL]. PLoS One, 2020, 15(5): e0233851 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/32470084/. DOI: 10.1371/journal.pone.0233851.
[26]
JUSTICE J A, SANCHEZ R M. A rat model of perinatal seizures provoked by global hypoxia[J/OL]. Methods Mol Biol, 2018, 1717: 155-159 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/29468591/. DOI: 10.1007/978-1-4939-7526-6_13.
[27]
POSPELOV A S, PUSKARJOV M, KAI K L, et al. Endogenous brain-sparing responses in brain pH and PO2 in a rodent model of birth asphyxia[J/OL]. Acta Physiol, 2020, 229(3) [2022-05-18]. https://onlinelibrary.wiley.com/doi/10.1111/apha.13467. DOI: 10.1111/apha.13467.
[28]
GAILUS B, NAUNDORF H, WELZEL L, et al. Long-term outcome in a noninvasive rat model of birth asphyxia with neonatal seizures: cognitive impairment, anxiety, epilepsy, and structural brain alterations[J]. Epilepsia, 2021, 62(11): 2826-2844. DOI: 10.1111/epi.17050.
[29]
BANO S, CHAUDHARY V, GARGA U C. Neonatal hypoxic-ischemic encephalopathy: a radiological review[J]. J Pediatr Neurosci, 2017, 12(1): 1-6. DOI: 10.4103/1817-1745.205646.
[30]
MACHIE M, WEEKE L, DE VRIES L S, et al. MRI score ability to detect abnormalities in mild hypoxic-ischemic encephalopathy[J/OL]. Pediatr Neurol, 2021, 116: 32-38 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/33412459/. DOI: 10.1016/j.pediatrneurol.2020.11.015.
[31]
LUPTAKOVA D, BACIAK L, PLUHACEK T, et al. Membrane depolarization and aberrant lipid distributions in the neonatal rat brain following hypoxic-ischaemic insult[J/OL]. Sci Rep, 2018, 8(1): 6952 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/29725040/. DOI: 10.1038/s41598-018-25088-2.
[32]
LODYGENSKY G A, INDER T E, NEIL J J. Application of magnetic resonance imaging in animal models of perinatal hypoxic-ischemic cerebral injury[J]. Int J Dev Neurosci, 2008, 26(1): 13-25. DOI: 10.1016/j.ijdevneu.2007.08.018.
[33]
YILDIZ E P, EKICI B, TATLI B. Neonatal hypoxic ischemic encephalopathy: an update on disease pathogenesis and treatment[J]. Expert Rev Neurother, 2017, 17(5): 449-459. DOI: 10.1080/14737175.2017.1259567.
[34]
ANNINK K V, DE VRIES L S, GROENENDAAL F, et al. Mammillary body atrophy and other MRI correlates of school-age outcome following neonatal hypoxic-ischemic encephalopathy[J/OL]. Sci Rep, 2021, 11: 5017 [2022-05-18]. https://www.nature.com/articles/s41598-021-83982-8. DOI: 10.1038/s41598-021-83982-8.
[35]
GERMONPRÉ C, PROESMANS S, BOUCKAERT C, et al. Seizures and interictal epileptiform activity in the rat collagenase model for intracerebral hemorrhage[J/OL]. Front Neurosci, 2021, 15: 682036 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/34220437/. DOI: 10.3389/fnins.2021.682036.
[36]
HOFFMANN A, KUNZE R, HELLUY X, et al. High-field MRI reveals a drastic increase of hypoxia-induced microhemorrhages upon tissue reoxygenation in the mouse brain with strong predominance in the olfactory bulb[J/OL]. PLoS One, 2016, 11(2): e0148441 [2022-05-18]. https://pubmed.ncbi.nlm.nih.gov/26863147/. DOI: 10.1371/journal.pone.0148441.

PREV Clinical value of diffusion tensor imaging in polymyositis and dermatomyositis
NEXT The evaluation and quantitative analysis of MR 3D-Vibe combined with T2 mapping imaging on triangular fibrocartilage complex injury of wrist joint
  



Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn