Abstract
Cathepsin B is one of the major lysosomal cysteine proteases involved in neuronal protein catabolism. This cathepsin is released after traumatic injury and increases neuronal death; however, release of cystatin C, a cathepsin inhibitor, appears to be a self-protective brain response. Here we describe the effect of cystatin C intracerebroventricular administration in rats prior to inducing a traumatic brain injury. We observed that cystatin C injection caused a dual response in post-traumatic brain injury recovery: higher doses (350 fmoles) increased bleeding and mortality, whereas lower doses (3.5 to 35 fmoles) decreased bleeding, neuronal damage and mortality. We also analyzed the expression of cathepsin B and cystatin C in the brains of control rats and of rats after a traumatic brain injury. Cathepsin B was detected in the brain stem, cerebellum, hippocampus and cerebral cortex of control rats. Cystatin C was localized to the choroid plexus, brain stem and cerebellum of control rats. Twenty-four hours after traumatic brain injury, we observed changes in both the expression and localization of both proteins in the cerebral cortex, hippocampus and brain stem. An early increase and intralysosomal expression of cystatin C after brain injury was associated with reduced neuronal damage.
Highlights
Traumatic brain injury (TBI) is one of the most important health problems in the world today
We observed significant differences in both the body weight (F5,118 = 39.35, p < 0.0001) and the food (F5,133 = 107.54, p < 0.0001) and water (F5,92 = 22.34, p < 0.0001) intake 24 h after TBI in all experimental groups compared to the control rats
We found that the administration of low doses of CC reduced this impairment, which is in agreement with effect of cystatin C in control rats
Summary
Traumatic brain injury (TBI) is one of the most important health problems in the world today. Self-protective mechanisms are induced by brain injury These mediators have damage-reducing properties and are endogenous efforts to counteract traumatic damage and improve neuronal repair [3]. Cathepsins are lysosomal cystein-proteases that appear to be released after traumatic injury and increase neuronal death; on the other hand, the release of cystatin C (CC), an endogenous inhibitor of cathepsins B, H, K, L, and S, appears to be a self-protective brain response [4]. We found that intracerebroventricular administration of a high dose of CC worsened TBI recovery [11], despite being one of the most potent endogenous inhibitors of cathepsin B [12], and decreased the central temperature [13] Considering all of these data, our study aimed to determine the effects of lower doses of CC during rat TBI recuperation.
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