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Effects of inosine on neuronal apoptosis and the expression of cytochrome C mRNA following hypoxic-ischemic brain damage in neonatal rats.
Zhongguo Dang Dai Er Ke Za Zhi. 2006 Aug; 8(4):266-71.ZD

Abstract

OBJECTIVE

It has been reported that neuronal apoptosis plays a critical role in pathology of hypoxic-ischemic encephalopathy (HIE). Cytochrome C (CytC) is an important apoptotic protease activating factor. Inosine might have a neuroprotective effect against cerebral ischemia reperfusion injury by inhibiting the neuronal apoptosis and the expression of CytC mRNA in adult rats. This study examined the effects of inosine on neuronal apoptosis and CytC mRNA expression following hypoxic-ischemic brain damage (HIBD) in order to investigate the neuroprotectivity of inosine against cerebral ischemia injury in neonatal rats and the possible mechanism.

METHODS

A total of 140 healthy 7-day-old Sprague-Dawley rat pups were randomly assigned into Control (n=40), HIBD (n=50) and Inosine treatment groups (n=50). HIBD rat models were established by ligating the left common carotid artery, followed by 8% O2 hypoxia exposure for 2 hrs in the HIBD and Inosine treatment groups. The Control group was not subjected to hypoxia-ischemia (HI). The Inosine treatment and the HIBD groups were randomly divided into 5 sub-groups sacrificed at 6 and 12 hrs, and 1, 3 and 7 days post- HI (n=10 each). The Control group rats were sacrificed at the corresponding time points (n=8 each). Inosine was administered to the Inosine treatment group by intraperitoneal injection immediately after HIBD at the dosage of 100 mg/kg twice daily for 7 days. TUNEL staining and in situ hybridization method was used to detect neuronal apoptosis and CytC mRNA expression respectively.

RESULTS

Few apoptotic cells and CytC mRNA positive cells were found in brain tissues of the Control group. In the HIBD group, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas increased 6 hrs after HI, peaking at 1 day after HI and then decreased gradually. Until the 7th day, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas in the HIBD group remained significantly higher than in the Control group. Inosine treatment decreased the apoptotic cells and the CytC mRNA expression in both areas from 6 hrs to 7 days after HI compared with the HIBD group. The linear correlation analysis demonstrated that the number of apoptotic cells was positively correlated to the CytC mRNA expression in neonatal rats with HIBD (r=0.88, P < 0.01) .

CONCLUSIONS

Inosine can reduce the number of apoptotic cells and down-regulate the expression of CytC mRNA following HIBD in neonatal rats. The decreased number of apoptotic cells was positively correlated to the decreased CytC mRNA expression after inosine treatment, suggesting that inosine offered neuroprotectivity against HIBD possibly through inhibiting the CytC mRNA expression and resulting in a decrease of cell apoptosis.

Authors+Show Affiliations

Department of Pediatrics, Third Xiangya Hospital of Central South University, Changsha 410013, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16923353

Citation

Deng, Yong-Hong, et al. "Effects of Inosine On Neuronal Apoptosis and the Expression of Cytochrome C mRNA Following Hypoxic-ischemic Brain Damage in Neonatal Rats." Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary Pediatrics, vol. 8, no. 4, 2006, pp. 266-71.
Deng YH, Kuang SJ, Hei MY, et al. Effects of inosine on neuronal apoptosis and the expression of cytochrome C mRNA following hypoxic-ischemic brain damage in neonatal rats. Zhongguo Dang Dai Er Ke Za Zhi. 2006;8(4):266-71.
Deng, Y. H., Kuang, S. J., Hei, M. Y., & Tian, L. (2006). Effects of inosine on neuronal apoptosis and the expression of cytochrome C mRNA following hypoxic-ischemic brain damage in neonatal rats. Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary Pediatrics, 8(4), 266-71.
Deng YH, et al. Effects of Inosine On Neuronal Apoptosis and the Expression of Cytochrome C mRNA Following Hypoxic-ischemic Brain Damage in Neonatal Rats. Zhongguo Dang Dai Er Ke Za Zhi. 2006;8(4):266-71. PubMed PMID: 16923353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of inosine on neuronal apoptosis and the expression of cytochrome C mRNA following hypoxic-ischemic brain damage in neonatal rats. AU - Deng,Yong-Hong, AU - Kuang,Shou-Jin, AU - Hei,Ming-Yan, AU - Tian,Lang, PY - 2006/8/23/pubmed PY - 2006/10/27/medline PY - 2006/8/23/entrez SP - 266 EP - 71 JF - Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics JO - Zhongguo Dang Dai Er Ke Za Zhi VL - 8 IS - 4 N2 - OBJECTIVE: It has been reported that neuronal apoptosis plays a critical role in pathology of hypoxic-ischemic encephalopathy (HIE). Cytochrome C (CytC) is an important apoptotic protease activating factor. Inosine might have a neuroprotective effect against cerebral ischemia reperfusion injury by inhibiting the neuronal apoptosis and the expression of CytC mRNA in adult rats. This study examined the effects of inosine on neuronal apoptosis and CytC mRNA expression following hypoxic-ischemic brain damage (HIBD) in order to investigate the neuroprotectivity of inosine against cerebral ischemia injury in neonatal rats and the possible mechanism. METHODS: A total of 140 healthy 7-day-old Sprague-Dawley rat pups were randomly assigned into Control (n=40), HIBD (n=50) and Inosine treatment groups (n=50). HIBD rat models were established by ligating the left common carotid artery, followed by 8% O2 hypoxia exposure for 2 hrs in the HIBD and Inosine treatment groups. The Control group was not subjected to hypoxia-ischemia (HI). The Inosine treatment and the HIBD groups were randomly divided into 5 sub-groups sacrificed at 6 and 12 hrs, and 1, 3 and 7 days post- HI (n=10 each). The Control group rats were sacrificed at the corresponding time points (n=8 each). Inosine was administered to the Inosine treatment group by intraperitoneal injection immediately after HIBD at the dosage of 100 mg/kg twice daily for 7 days. TUNEL staining and in situ hybridization method was used to detect neuronal apoptosis and CytC mRNA expression respectively. RESULTS: Few apoptotic cells and CytC mRNA positive cells were found in brain tissues of the Control group. In the HIBD group, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas increased 6 hrs after HI, peaking at 1 day after HI and then decreased gradually. Until the 7th day, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas in the HIBD group remained significantly higher than in the Control group. Inosine treatment decreased the apoptotic cells and the CytC mRNA expression in both areas from 6 hrs to 7 days after HI compared with the HIBD group. The linear correlation analysis demonstrated that the number of apoptotic cells was positively correlated to the CytC mRNA expression in neonatal rats with HIBD (r=0.88, P < 0.01) . CONCLUSIONS: Inosine can reduce the number of apoptotic cells and down-regulate the expression of CytC mRNA following HIBD in neonatal rats. The decreased number of apoptotic cells was positively correlated to the decreased CytC mRNA expression after inosine treatment, suggesting that inosine offered neuroprotectivity against HIBD possibly through inhibiting the CytC mRNA expression and resulting in a decrease of cell apoptosis. SN - 1008-8830 UR - https://www.unboundmedicine.com/medline/citation/16923353/Effects_of_inosine_on_neuronal_apoptosis_and_the_expression_of_cytochrome_C_mRNA_following_hypoxic_ischemic_brain_damage_in_neonatal_rats_ DB - PRIME DP - Unbound Medicine ER -