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Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest.

Zhang YP, Zhu YB, Duan DD, Fan XM, He Y, Su JW, Liu YL - Int J Med Sci (2015)

Bottom Line: DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05).Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA.The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.

View Article: PubMed Central - PubMed

Affiliation: 1. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029.

ABSTRACT

Background: Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death. We studied the hypothesis that UCH-L1 may be a potential biomarker for DHCA-induced ischemic neuronal apoptosis.

Methods: Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis.

Results: DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05). Positive correlation was obtained between serum UCH-L1 level and the severity of neuron apoptosis (r= 0.78, P<0.01). By ROC, the area under the curve were 0.88 (95% CI: 0.74-0.99; P<0.01), 0.81 (95% CI: 0.81-0.96; P<0.05), 0.71 (95% CI: 0.47-0.92; P=0.11) for UCH-L1, Bax/Bcl-2 ratio and Bax, respectively. Using a cut-off point of 0.25, the UCH-L1 predicted neuronal apoptosis with a sensitivity of 85% and specificity of 57%.

Conclusion: Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA. The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.

No MeSH data available.


Related in: MedlinePlus

Neuronal apoptosis detected by TUNEL analysis. A. sham group; B. CPB group; C. DHCA group. Neurons containing brown yellow granules in nuclei were considered as positive apoptotic cells.
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Figure 2: Neuronal apoptosis detected by TUNEL analysis. A. sham group; B. CPB group; C. DHCA group. Neurons containing brown yellow granules in nuclei were considered as positive apoptotic cells.

Mentions: Neuronal cell death in DHCA group was severer than CPB and sham control groups (Figure 1). TUNEL assay showed that neuronal apoptosis was apparent in DHCA group whereas neuronal apoptosis was not observed in sham control group and rarely in CPB group (Figure 2). Neuronal death scores were significantly increased in both CPB and DHCA groups compared to sham operated control (Figure 3A). Furthermore, the neuronal death was more pronounced in DHCA compared to CPB alone (3.2±0.5 vs 1.6±0.7, P<0.05, Figure 3A). The number of apoptotic neurons in DHCA group was much greater than CPB and sham control groups (28±9 vs 18±7 and 2±1, all P<0.05, Figure 3B). The Bax protein expression did not change among three groups (P>0.05, Figure 4). However, Bcl-2 expression was significantly decreased in DHCA group (all P<0.05, DHCA vs CPB and Sham control, Figure 4). Hence, Bax:Bcl-2 ratio was increased in DHCA group (all P<0.05, DHCA vs CPB and Sham control, Figure 4).


Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest.

Zhang YP, Zhu YB, Duan DD, Fan XM, He Y, Su JW, Liu YL - Int J Med Sci (2015)

Neuronal apoptosis detected by TUNEL analysis. A. sham group; B. CPB group; C. DHCA group. Neurons containing brown yellow granules in nuclei were considered as positive apoptotic cells.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4502062&req=5

Figure 2: Neuronal apoptosis detected by TUNEL analysis. A. sham group; B. CPB group; C. DHCA group. Neurons containing brown yellow granules in nuclei were considered as positive apoptotic cells.
Mentions: Neuronal cell death in DHCA group was severer than CPB and sham control groups (Figure 1). TUNEL assay showed that neuronal apoptosis was apparent in DHCA group whereas neuronal apoptosis was not observed in sham control group and rarely in CPB group (Figure 2). Neuronal death scores were significantly increased in both CPB and DHCA groups compared to sham operated control (Figure 3A). Furthermore, the neuronal death was more pronounced in DHCA compared to CPB alone (3.2±0.5 vs 1.6±0.7, P<0.05, Figure 3A). The number of apoptotic neurons in DHCA group was much greater than CPB and sham control groups (28±9 vs 18±7 and 2±1, all P<0.05, Figure 3B). The Bax protein expression did not change among three groups (P>0.05, Figure 4). However, Bcl-2 expression was significantly decreased in DHCA group (all P<0.05, DHCA vs CPB and Sham control, Figure 4). Hence, Bax:Bcl-2 ratio was increased in DHCA group (all P<0.05, DHCA vs CPB and Sham control, Figure 4).

Bottom Line: DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05).Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA.The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.

View Article: PubMed Central - PubMed

Affiliation: 1. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029.

ABSTRACT

Background: Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death. We studied the hypothesis that UCH-L1 may be a potential biomarker for DHCA-induced ischemic neuronal apoptosis.

Methods: Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis.

Results: DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05). Positive correlation was obtained between serum UCH-L1 level and the severity of neuron apoptosis (r= 0.78, P<0.01). By ROC, the area under the curve were 0.88 (95% CI: 0.74-0.99; P<0.01), 0.81 (95% CI: 0.81-0.96; P<0.05), 0.71 (95% CI: 0.47-0.92; P=0.11) for UCH-L1, Bax/Bcl-2 ratio and Bax, respectively. Using a cut-off point of 0.25, the UCH-L1 predicted neuronal apoptosis with a sensitivity of 85% and specificity of 57%.

Conclusion: Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA. The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.

No MeSH data available.


Related in: MedlinePlus