Open Access

Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice

  • Authors:
    • Changbo Deng
    • Juan Li
    • Luyi Li
    • Fengjie Sun
    • Jiqing Xie
  • View Affiliations

  • Published online on: April 15, 2019     https://doi.org/10.3892/etm.2019.7487
  • Pages: 4517-4521
  • Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice were investigated. Twenty-five neonatal CD1 mice aged 1 week were selected and randomly divided into sham-operation group (n=8) and newborn hypoxia ischemia encephalopathy (NHIE) model group (n=17). The messenger ribonucleic acid (mRNA) expression levels of caspase-3 and Fas ligand (FasL) in brain tissues of mice in both groups were detected via reverse transcription-polymerase chain reaction (RT-PCR). The protein expression levels of caspase-3 and FasL in mice in both groups were detected via western blotting. Moreover, apoptosis of brain tissues was detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and caspase-3 protein expression level in brain tissues was detected using immunohistochemical methods. Results of RT-PCR and western blotting revealed that compared with those in sham-operation group, caspase-3 and FasL expression levels in model group were significantly increased. Results of TUNEL showed that the number of apoptotic neurons in model group was significantly increased. Besides, results of immunohistochemical detection manifested that the caspase-3 protein expression level in model group was obviously increased. Hypoxia ischemia can lead to significant increase of caspase-3 expression and increase of neuronal apoptosis in the brain of neonatal mice.

References

1 

Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, et al: Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: Multicentre randomised trial. Lancet. 365:663–670. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Zheng H, Dai T, Zhou B, Zhu J, Huang H, Wang M and Fu G: SDF-1alpha/CXCR4 decreases endothelial progenitor cells apoptosis under serum deprivation by PI3K/Akt/eNOS pathway. Atherosclerosis. 201:36–42. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Miller JT, Bartley JH, Wimborne HJ, Walker AL, Hess DC, Hill WD and Carroll JE: The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury. BMC Neurosci. 6:632005. View Article : Google Scholar : PubMed/NCBI

4 

Northington FJ, Ferriero DM, Flock DL and Martin LJ: Delayed neurodegeneration in neonatal rat thalamus after hypoxia-ischemia is apoptosis. J Neurosci. 21:1931–1938. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Stumm RK, Rummel J, Junker V, Culmsee C, Pfeiffer M, Krieglstein J, Höllt V and Schulz S: A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: Isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. J Neurosci. 22:5865–5878. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Shyu WC, Lin SZ, Yen PS, Su CY, Chen DC, Wang HJ and Li H: Stromal cell-derived factor-1 alpha promotes neuroprotection, angiogenesis, and mobilization/homing of bone marrow-derived cells in stroke rats. J Pharmacol Exp Ther. 324:834–849. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Andiné P, Thordstein M, Kjellmer I, Nordborg C, Thiringer K, Wennberg E and Hagberg H: Evaluation of brain damage in a rat model of neonatal hypoxic-ischemia. J Neurosci Methods. 35:253–260. 1990. View Article : Google Scholar : PubMed/NCBI

8 

Johnston MV: Neurotransmitter alterations in a model of perinatal hypoxic-ischemic brain injury. Ann Neurol. 13:511–518. 1983. View Article : Google Scholar : PubMed/NCBI

9 

Ren C, Du A, Li D, Sui J, Mayhan WG and Zhao H: Dynamic change of hydrogen sulfide during global cerebral ischemia-reperfusion and its effect in rats. Brain Res. 1345:197–205. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Kilicdag H, Daglioglu YK, Erdogan S and Zorludemir S: Effects of caffeine on neuronal apoptosis in neonatal hypoxic-ischemic brain injury. J Matern Fetal Neonatal Med. 27:1470–1475. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Zhu M, Lu M, Li QJ, Zhang Z, Wu ZZ, Li J, Qian L, Xu Y and Wang ZY: Hyperbaric oxygen suppresses hypoxic-ischemic brain damage in newborn rats. J Child Neurol. 30:75–82. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Rice JE III, Vannucci RC and Brierley JB: The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol. 9:131–141. 1981. View Article : Google Scholar : PubMed/NCBI

13 

Levine S: Anoxic-ischemic encephalopathy in rats. Am J Pathol. 36:1–17. 1960.PubMed/NCBI

14 

Cowan CM, Thai J, Krajewski S, Reed JC, Nicholson DW, Kaufmann SH and Roskams AJ: Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons. J Neurosci. 21:7099–7109. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Berger R and Garnier Y: Perinatal brain injury. J Perinat Med. 28:261–285. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Cheng Y, Deshmukh M, D'Costa A, Demaro JA, Gidday JM, Shah A, Sun Y, Jacquin MF, Johnson EM and Holtzman DM: Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury. J Clin Invest. 101:1992–1999. 1998. View Article : Google Scholar : PubMed/NCBI

17 

Wang J, Van De Water TR, Bonny C, de Ribaupierre F, Puel JL and Zine A: A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J Neurosci. 23:8596–8607. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Han W, Sun Y, Wang X, Zhu C and Blomgren K: Delayed, long-term administration of the caspase inhibitor Q-VD-OPh reduced brain injury induced by neonatal hypoxia-ischemia. Dev Neurosci. 36:64–72. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Wang X, Guo S, Lu S, Zhou J, Li J and Xia S: Ultrasound-induced release of GDNF from lipid coated microbubbles injected into striatum reduces hypoxic-ischemic injury in neonatal rats. Brain Res Bull. 88:495–500. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Xiao A, Kang M, Zhang H and Gong L: Effects of moxibustion pretreatment on caspase-3 expression in cortex of rats with cerebral ischemia-reperfusion injury. Tianjin Zhong Yi Yao. 42:550–552. 2014.(In Chinese).

Related Articles

Journal Cover

June 2019
Volume 17 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Deng, C., Li, J., Li, L., Sun, F., & Xie, J. (2019). Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice. Experimental and Therapeutic Medicine, 17, 4517-4521. https://doi.org/10.3892/etm.2019.7487
MLA
Deng, C., Li, J., Li, L., Sun, F., Xie, J."Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice". Experimental and Therapeutic Medicine 17.6 (2019): 4517-4521.
Chicago
Deng, C., Li, J., Li, L., Sun, F., Xie, J."Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice". Experimental and Therapeutic Medicine 17, no. 6 (2019): 4517-4521. https://doi.org/10.3892/etm.2019.7487