Limits...
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.

Show MeSH

Related in: MedlinePlus

Neurological severity score (NSS) and grip test. (a) At 24 h after traumatic brain injury (TBI), mice pretreated with LHVS had significantly better neurological function than did mice pretreated with vehicle, as assessed by the NSS (a) and the grip test (b). At 3 days after TBI, function had improved in both groups. At this time point, neurological function was still slightly better in the LHVS-pretreated group, but the difference was significant only in the grip test. Data are presented as mean ± SEM (n = 6). *P < 0.05, ***P < 0.001 versus TBI + vehicle; two-way ANOVA followed by Bonferroni post hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3824312&req=5

fig8: Neurological severity score (NSS) and grip test. (a) At 24 h after traumatic brain injury (TBI), mice pretreated with LHVS had significantly better neurological function than did mice pretreated with vehicle, as assessed by the NSS (a) and the grip test (b). At 3 days after TBI, function had improved in both groups. At this time point, neurological function was still slightly better in the LHVS-pretreated group, but the difference was significant only in the grip test. Data are presented as mean ± SEM (n = 6). *P < 0.05, ***P < 0.001 versus TBI + vehicle; two-way ANOVA followed by Bonferroni post hoc test.

Mentions: At 24 h after TBI, the NSS score of the LHVS-treated mice was significantly better than that of the vehicle-treated mice (Figure 8(a)). At 3 days, the scores of both groups had improved, and although a difference was still detectable, it was not statistically significant. In the grip test, the scores of the LHVS-treated mice were significantly better than those of the vehicle-treated mice at both 24 h and 3 days after TBI (Figure 8(b)). As in the NSS, the scores of both groups were better at 3 days than at 24 h.


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)

Neurological severity score (NSS) and grip test. (a) At 24 h after traumatic brain injury (TBI), mice pretreated with LHVS had significantly better neurological function than did mice pretreated with vehicle, as assessed by the NSS (a) and the grip test (b). At 3 days after TBI, function had improved in both groups. At this time point, neurological function was still slightly better in the LHVS-pretreated group, but the difference was significant only in the grip test. Data are presented as mean ± SEM (n = 6). *P < 0.05, ***P < 0.001 versus TBI + vehicle; two-way ANOVA followed by Bonferroni post hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig8: Neurological severity score (NSS) and grip test. (a) At 24 h after traumatic brain injury (TBI), mice pretreated with LHVS had significantly better neurological function than did mice pretreated with vehicle, as assessed by the NSS (a) and the grip test (b). At 3 days after TBI, function had improved in both groups. At this time point, neurological function was still slightly better in the LHVS-pretreated group, but the difference was significant only in the grip test. Data are presented as mean ± SEM (n = 6). *P < 0.05, ***P < 0.001 versus TBI + vehicle; two-way ANOVA followed by Bonferroni post hoc test.
Mentions: At 24 h after TBI, the NSS score of the LHVS-treated mice was significantly better than that of the vehicle-treated mice (Figure 8(a)). At 3 days, the scores of both groups had improved, and although a difference was still detectable, it was not statistically significant. In the grip test, the scores of the LHVS-treated mice were significantly better than those of the vehicle-treated mice at both 24 h and 3 days after TBI (Figure 8(b)). As in the NSS, the scores of both groups were better at 3 days than at 24 h.

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