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Inhibition of cathepsin S produces neuroprotective effects after traumatic brain injury in mice.

Xu J, Wang H, Ding K, Lu X, Li T, Wang J, Wang C, Wang J - Mediators Inflamm. (2013)

Bottom Line: The increased expression was detected in microglia and neurons.Inhibition of CatS significantly reduced the level of TBI-induced inflammatory factors in brain tissue and alleviated brain edema.Additionally, administration of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral function.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.

ABSTRACT
Cathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has long been regarded as an enzyme that is primarily involved in general protein degradation. More recently, mounting evidence has shown that it is involved in Alzheimer disease, seizures, age-related inflammatory processes, and neuropathic pain. In this study, we investigated the time course of CatS protein and mRNA expression and the cellular distribution of CatS in a mouse model of traumatic brain injury (TBI). To clarify the roles of CatS in TBI, we injected the mice intraventricularly with LHVS, a nonbrain penetrant, irreversible CatS inhibitor, and examined the effect on inflammation and neurobehavioral function. We found that expression of CatS was increased as early as 1 h after TBI at both protein and mRNA levels. The increased expression was detected in microglia and neurons. Inhibition of CatS significantly reduced the level of TBI-induced inflammatory factors in brain tissue and alleviated brain edema. Additionally, administration of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral function. These results imply that CatS is involved in the secondary injury after TBI and provide a new perspective for preventing secondary injury after TBI.

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Related in: MedlinePlus

Time course of cathepsin S (CatS) mRNA expression in the ipsilateral cortex of mice after traumatic brain injury (TBI). The level of CatS mRNA was significantly increased at 3 h after TBI as compared with that in the sham group. β-actin was used as an internal control. The data were normalized to β-actin expression and were expressed as fold increase of the sham group. Data represent mean ± SEM (n = 6). *P < 0.05 versus sham group.
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fig2: Time course of cathepsin S (CatS) mRNA expression in the ipsilateral cortex of mice after traumatic brain injury (TBI). The level of CatS mRNA was significantly increased at 3 h after TBI as compared with that in the sham group. β-actin was used as an internal control. The data were normalized to β-actin expression and were expressed as fold increase of the sham group. Data represent mean ± SEM (n = 6). *P < 0.05 versus sham group.

Mentions: The changes in CatS protein level after TBI may result from activation of pre-CatS. Therefore, we used real-time quantitative PCR to determine whether CatS expression also changed at the mRNA level. CatS mRNA began to increase as early as 1 h after TBI (Figure 2). At 3 h after TBI, it reached a peak that was approximately 2-fold the level of the sham group (P < 0.05). The CatS mRNA level had begun to decrease by 6 h, and by 12 h, it was not different from that of the sham group (P > 0.05).


Inhibition of cathepsin S produces neuroprotective effects after traumatic brain injury in mice.

Xu J, Wang H, Ding K, Lu X, Li T, Wang J, Wang C, Wang J - Mediators Inflamm. (2013)

Time course of cathepsin S (CatS) mRNA expression in the ipsilateral cortex of mice after traumatic brain injury (TBI). The level of CatS mRNA was significantly increased at 3 h after TBI as compared with that in the sham group. β-actin was used as an internal control. The data were normalized to β-actin expression and were expressed as fold increase of the sham group. Data represent mean ± SEM (n = 6). *P < 0.05 versus sham group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824312&req=5

fig2: Time course of cathepsin S (CatS) mRNA expression in the ipsilateral cortex of mice after traumatic brain injury (TBI). The level of CatS mRNA was significantly increased at 3 h after TBI as compared with that in the sham group. β-actin was used as an internal control. The data were normalized to β-actin expression and were expressed as fold increase of the sham group. Data represent mean ± SEM (n = 6). *P < 0.05 versus sham group.
Mentions: The changes in CatS protein level after TBI may result from activation of pre-CatS. Therefore, we used real-time quantitative PCR to determine whether CatS expression also changed at the mRNA level. CatS mRNA began to increase as early as 1 h after TBI (Figure 2). At 3 h after TBI, it reached a peak that was approximately 2-fold the level of the sham group (P < 0.05). The CatS mRNA level had begun to decrease by 6 h, and by 12 h, it was not different from that of the sham group (P > 0.05).

Bottom Line: The increased expression was detected in microglia and neurons.Inhibition of CatS significantly reduced the level of TBI-induced inflammatory factors in brain tissue and alleviated brain edema.Additionally, administration of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral function.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.

ABSTRACT
Cathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has long been regarded as an enzyme that is primarily involved in general protein degradation. More recently, mounting evidence has shown that it is involved in Alzheimer disease, seizures, age-related inflammatory processes, and neuropathic pain. In this study, we investigated the time course of CatS protein and mRNA expression and the cellular distribution of CatS in a mouse model of traumatic brain injury (TBI). To clarify the roles of CatS in TBI, we injected the mice intraventricularly with LHVS, a nonbrain penetrant, irreversible CatS inhibitor, and examined the effect on inflammation and neurobehavioral function. We found that expression of CatS was increased as early as 1 h after TBI at both protein and mRNA levels. The increased expression was detected in microglia and neurons. Inhibition of CatS significantly reduced the level of TBI-induced inflammatory factors in brain tissue and alleviated brain edema. Additionally, administration of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral function. These results imply that CatS is involved in the secondary injury after TBI and provide a new perspective for preventing secondary injury after TBI.

Show MeSH
Related in: MedlinePlus