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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 of brain tissue from mice at 3 h after traumatic brain injury (TBI) or sham injury. Images show double immunofluorescent staining for cathepsin S (CatS; green) and different neural cell markers (red). Nuclei were counterstained with DAPI in the same view in each section. CatS staining was weak in the sham group but enhanced in the cytoplasm of the TBI group. Arrows indicate colocalization of CatS and ED1 or NeuN. Scale bars: 50 µm.
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fig4: Representative photomicrographs of brain tissue from mice at 3 h after traumatic brain injury (TBI) or sham injury. Images show double immunofluorescent staining for cathepsin S (CatS; green) and different neural cell markers (red). Nuclei were counterstained with DAPI in the same view in each section. CatS staining was weak in the sham group but enhanced in the cytoplasm of the TBI group. Arrows indicate colocalization of CatS and ED1 or NeuN. Scale bars: 50 µm.

Mentions: To clarify the neural expression of CatS after TBI, we performed double immunofluorescent staining for CatS and cell-specific markers ED1, NeuN, and GFAP. As shown in Figure 4, CatS was expressed weakly in the sham group, consistent with the results of immunohistochemistry. However, CatS-positive cells were present in tissue from the 3 h after TBI group. The morphology indicated that CatS was expressed in cytoplasm. Overlapping images show that CatS was mainly expressed in ED1-positive cells and to a lesser extent in NeuN-positive cells. These results suggested that CatS is expressed mainly in microglia in the cortex 3 h after TBI.


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 of brain tissue from mice at 3 h after traumatic brain injury (TBI) or sham injury. Images show double immunofluorescent staining for cathepsin S (CatS; green) and different neural cell markers (red). Nuclei were counterstained with DAPI in the same view in each section. CatS staining was weak in the sham group but enhanced in the cytoplasm of the TBI group. Arrows indicate colocalization of CatS and ED1 or NeuN. Scale bars: 50 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Representative photomicrographs of brain tissue from mice at 3 h after traumatic brain injury (TBI) or sham injury. Images show double immunofluorescent staining for cathepsin S (CatS; green) and different neural cell markers (red). Nuclei were counterstained with DAPI in the same view in each section. CatS staining was weak in the sham group but enhanced in the cytoplasm of the TBI group. Arrows indicate colocalization of CatS and ED1 or NeuN. Scale bars: 50 µm.
Mentions: To clarify the neural expression of CatS after TBI, we performed double immunofluorescent staining for CatS and cell-specific markers ED1, NeuN, and GFAP. As shown in Figure 4, CatS was expressed weakly in the sham group, consistent with the results of immunohistochemistry. However, CatS-positive cells were present in tissue from the 3 h after TBI group. The morphology indicated that CatS was expressed in cytoplasm. Overlapping images show that CatS was mainly expressed in ED1-positive cells and to a lesser extent in NeuN-positive cells. These results suggested that CatS is expressed mainly in microglia in the cortex 3 h after TBI.

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