Effects of Hemin on neuroglobin expression after cardiopulmonary resuscitation in rats

Abstract

Abstract:

BACKGROUND: Despite a large amount of resuscitation research, the survival rate after cardiac arrest remains low, and brain injury is the key issue. Neuroglobin (NGB) is an oxygen-binding heme protein found in the brain with a protection role against ischemic-hypoxic brain injury. Hemin is an effective activator of neuroglobin. This study was undertaken to assess the effect of hemin on expression of neuroglobin (NGB) in the cerebral cortex, neuro-deficit score (NDS) and pathological changes after cardiopulmonary resuscitation (CPR) in rats.
METHODS: A total of 120 male Sprague-Dawley (SD) rats were randomly divided into a control group (A), a CPR group (B) and a Hemin group (C). The animal model of cardiac arrest (CA) induced by asphyxia and CPR was established. NGB expression in the cerebral cortex with immunohistochemistry, NDS and pathological changes in the cerebral cortex were examined at 3, 6, 12, 24 hours after recovery of spontaneous circulation (ROSC) in each group. Experimental data were treated as one-factor analysis of variance and the Tukey test.
RESULTS: In comparison with group A, NGB expression was increased significantly at 12 and 24 hours after ROSC (P<0.05 or P<0.01), NDS was decreased significantly at each time point after ROSC (P<0.01), and pathological changes were severe at each time point after ROSC in group B. In comparison with group A, NGB expression was increased significantly at 6, 12, 24 hours after ROSC (P<0.05 or P<0.01), NDS was decreased significantly at 3, 6, 12 hours after ROSC (P<0.01) in group C. In comparison with group B, NGB expression was increased significantly at 12 and 24 hours after ROSC, NDS was increased significantly at 12 and 24 hours after ROSC, and pathological changes were milder in group C.
CONCLUSION: There were increased NGB expression in the cerebral cortex, decreased NDS, and severe pathological changes after CPR in rats. Hemin treatment up-regulated expression of NGB, improved NDS, mitigated pathological changes, and alleviated cerebral injury after CPR.

Key words: Cardiopulmonary resuscitation, Neuroglobin, Neurodeficit score, Hemin, Cerebral injury, Rats

Ai-wen He, Ting Yang, Shou-quan Chen, Zhang-ping Li, Hui-ping Li, Wei-jia Huang, Jun-yan Cheng, Jie Zhang, Ping Yang, Wan-tie Wang. Effects of Hemin on neuroglobin expression after cardiopulmonary resuscitation in rats[J]. World Journal of Emergency Medicine, 2011, 2(1): 54-58.

Figures/Tables 4

Table 1

Figure 1.

Table 2

Figure 2.

References 15

1	Burmester T, Weich B, Reinhardt S, Hankeln T. A vertebrate globin expressed in the brain. Nature 2000; 407:520-523. pmid: 11029004
2	Burmester T, Hankeln T. What is the function of neuroglobin?. J Exp Biol 2009; 212:1423-1428. doi: 10.1242/jeb.000729 pmid: 19411534
3	Lakkisto P, Csonka C, Fodor G, Bencsik P, Voipio-Pulkki LM, Ferdinandy P, et al. The heme oxygenase inducer hemin protects against cardiac dysfunction and ventricular fibrillation in ischaemic/reperfused rat hearts: role of connexin 43. Scand J Clin Lab Invest 2009; 69:209-218. doi: 10.1080/00365510802474392 pmid: 18946777
4	Cheng SQ, Li ZP, Wang SS, Murao Y. Factors influencing asphyxial cardiac arrest. Emerg Med J China 2005; 14:814-817.
5	Idris AH, Becker LB, Ornato JP, Hedges JR, Bircher NG, Chandra NC, et al. Utstein-style guidelines for uniform reporting of laboratory CPR research. Circulation 1996; 94:2324-2336. pmid: 8901707
6	Geocadin RG, Malhotra AD, Tong S, Seth A, Moriwaki G, Hanley DF, et al. Effect of acute hypoxic preconditioning on qEEG and functional recovery after cardiac arrest in rats. Brain Research 2005; 1064:146-154. pmid: 16289119
7	Hua S, Antao ST, Corbett A, Witting PK. The significance of neuroglobin in the brain. Current Medicinal Chemistry 2010; 17:160-172. doi: 10.2174/092986710790112611 pmid: 19941472
8	Xu J, Yin G, Huang F, Dewilde S, Hay-Schmidt A. Neuroglobin expression in the rat suprachiasmatic nucleus: colocalization, innervation, and response to light. J Comp Neurol 2010; 518:1556-1569. pmid: 20187147
9	Jin K, Mao XO, Xie L, John V, Greenberg DA. Pharmacological induction of neuroglobin expression. Pharmacology 2011; 87: 81-84. [Epub ahead of print] pmid: 21228614
10	Jin K, Mao Y, Mao X, Xie L, Greenberg DA. Neuroglobin expression in ischemic stroke. Stroke 2010; 41:557-559. doi: 10.1161/STROKEAHA.109.567149 pmid: 20075359
11	Shang AJ, Zhou DB, Wang LH, Gao Y, Fan M, Wang X, et al. Increased neuroglobin levels in the cerebral cortex and serum after ischemia-reperfusion insults. Brain Research 2006; 1078:219-226. pmid: 16492379
12	Schneider A, Bottiger BW, Popp E. Cerebral resuscitation after cardiocirculatory arrest. Anesth Analg 2009; 108:971-979. pmid: 19224811
13	Menzebach A, Bergt S, von Waldthausen P, Dinu C, Nöldge-Schomburg G, Vollmar B. A comprehensive study of survival, tissue damage, and neurological dysfunction in a murine model of cardiopulmonary resuscitation after potassium-induced cardiac arrest. Shock 2010; 33:189-196. doi: 10.1097/SHK.0b013e3181ad59a3 pmid: 19487971
14	Du HG, Yin LC, He M, Zhang GJ, Tian Y, Wang C, et al. Application of ulinastatin in severe craniocerebral injuries. Chin J Traumatol 2005; 8:236-239. pmid: 16042871
15	Zhu Y, Sun Y, Jin K, Greenberg DA. Hemin induces neuroglobin expression in neural cells. Blood 2002; 100:2494-2498. pmid: 12239161

Groups	After ROSC
Groups	0.5 h	3 h	6 h	12 h	24 h
A	127.13±5.94	129.88±5.33	127.50±6.02	130.03±7.23	129.00±5.78
B	130.25±4.10	132.63±8.16	133.38±3.46	141.88±6.69^*ΔΔ	204.50±5.26^**ΔΔ
C	132.13±4.55	133.13±4.65	138.85±4.49^*Δ	152.13±8.06^**ΔΔ☆	216.75±6.82^**ΔΔ☆☆

Groups	After ROSC
Groups	3 h	6 h	12 h	24 h
A	76.00±1.69	76.63±1.68	76.85±1.72	77.11±1.34
B	51.13±1.13^#	60.62±1.58^*#	68.00±1.31^*#	72.88±1.25^*#
C	53.25±1.67^#	62.75±0.89^*#Δ	71.75±1.67^*#ΔΔ	76.00±1.07^*ΔΔ

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