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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

LHVS reduces cerebral edema in the ipsilateral cortex 24 h after traumatic brain injury (TBI). Brain water content was significantly higher in the TBI and TBI + vehicle groups than in the sham group. Pretreatment with LHVS significantly attenuated brain water content in the ipsilateral cortex compared with vehicle pretreatment. Data are presented as mean ± SEM. **P < 0.01, ***P < 0.001 versus sham group (n = 5); #P < 0.05 versus TBI + vehicle group.
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fig6: LHVS reduces cerebral edema in the ipsilateral cortex 24 h after traumatic brain injury (TBI). Brain water content was significantly higher in the TBI and TBI + vehicle groups than in the sham group. Pretreatment with LHVS significantly attenuated brain water content in the ipsilateral cortex compared with vehicle pretreatment. Data are presented as mean ± SEM. **P < 0.01, ***P < 0.001 versus sham group (n = 5); #P < 0.05 versus TBI + vehicle group.

Mentions: To confirm the protective effect of LHVS at the macroscopic level, we measured the brain water content of mice pretreated with vehicle or LHVS. Six groups were used as described in Section 3.5 (n = 5/group). Compared with the sham group, mice in the TBI and TBI + vehicle groups had significantly greater brain water content. The brain water content did not differ significantly between the TBI group and the TBI + vehicle group. However, consistent with the changes observed in proinflammatory factors, groups treated with 30 nM and 50 nM LHVS had significantly less brain water content than did the TBI + vehicle group (P < 0.05; Figure 6).


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)

LHVS reduces cerebral edema in the ipsilateral cortex 24 h after traumatic brain injury (TBI). Brain water content was significantly higher in the TBI and TBI + vehicle groups than in the sham group. Pretreatment with LHVS significantly attenuated brain water content in the ipsilateral cortex compared with vehicle pretreatment. Data are presented as mean ± SEM. **P < 0.01, ***P < 0.001 versus sham group (n = 5); #P < 0.05 versus TBI + vehicle group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: LHVS reduces cerebral edema in the ipsilateral cortex 24 h after traumatic brain injury (TBI). Brain water content was significantly higher in the TBI and TBI + vehicle groups than in the sham group. Pretreatment with LHVS significantly attenuated brain water content in the ipsilateral cortex compared with vehicle pretreatment. Data are presented as mean ± SEM. **P < 0.01, ***P < 0.001 versus sham group (n = 5); #P < 0.05 versus TBI + vehicle group.
Mentions: To confirm the protective effect of LHVS at the macroscopic level, we measured the brain water content of mice pretreated with vehicle or LHVS. Six groups were used as described in Section 3.5 (n = 5/group). Compared with the sham group, mice in the TBI and TBI + vehicle groups had significantly greater brain water content. The brain water content did not differ significantly between the TBI group and the TBI + vehicle group. However, consistent with the changes observed in proinflammatory factors, groups treated with 30 nM and 50 nM LHVS had significantly less brain water content than did the TBI + vehicle group (P < 0.05; Figure 6).

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