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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

Representative photomicrographs showing cathepsin S (CatS) immunohistochemistry of tissue from the sham and traumatic brain injury (TBI) groups. In the sham group, almost none of the cells presented a positive morphology, whereas, in the TBI group, many cells were positive for CatS. CatS was present mainly in the cytoplasm. The CatS-positive cells in the TBI group (indicated by arrows) showed two populations of cells with different morphologies.
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fig3: Representative photomicrographs showing cathepsin S (CatS) immunohistochemistry of tissue from the sham and traumatic brain injury (TBI) groups. In the sham group, almost none of the cells presented a positive morphology, whereas, in the TBI group, many cells were positive for CatS. CatS was present mainly in the cytoplasm. The CatS-positive cells in the TBI group (indicated by arrows) showed two populations of cells with different morphologies.

Mentions: We used immunohistochemistry to further clarify the change in expression of CatS protein. As shown in Figure 3, CatS was weakly expressed in the cortex of the normal (sham) mouse brain. At 3 h after TBI, the expression of CatS was significantly increased in the pericontusional cortex, mainly in the cytoplasm. The CatS-positive cells in the TBI group (indicated by arrows) showed two populations of cells with different morphologies, which might represent microglia and neurons, respectively. When the primary antibody was omitted from the immunostaining reaction, no immunoreactivity was present, suggesting high specificity of the antibody to the antigen (data not shown).


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)

Representative photomicrographs showing cathepsin S (CatS) immunohistochemistry of tissue from the sham and traumatic brain injury (TBI) groups. In the sham group, almost none of the cells presented a positive morphology, whereas, in the TBI group, many cells were positive for CatS. CatS was present mainly in the cytoplasm. The CatS-positive cells in the TBI group (indicated by arrows) showed two populations of cells with different morphologies.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Representative photomicrographs showing cathepsin S (CatS) immunohistochemistry of tissue from the sham and traumatic brain injury (TBI) groups. In the sham group, almost none of the cells presented a positive morphology, whereas, in the TBI group, many cells were positive for CatS. CatS was present mainly in the cytoplasm. The CatS-positive cells in the TBI group (indicated by arrows) showed two populations of cells with different morphologies.
Mentions: We used immunohistochemistry to further clarify the change in expression of CatS protein. As shown in Figure 3, CatS was weakly expressed in the cortex of the normal (sham) mouse brain. At 3 h after TBI, the expression of CatS was significantly increased in the pericontusional cortex, mainly in the cytoplasm. The CatS-positive cells in the TBI group (indicated by arrows) showed two populations of cells with different morphologies, which might represent microglia and neurons, respectively. When the primary antibody was omitted from the immunostaining reaction, no immunoreactivity was present, suggesting high specificity of the antibody to the antigen (data not shown).

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