Assessment of the Correlations Between Brain Weight and Brain Edema in Experimental Subarachnoid Hemorrhage.

Because brain edema is correlated with poor outcome in clinical subarachnoid hemorrhage (SAH), appropriate evaluation methods for brain edema are important in experimental SAH studies. Although brain water content (BWC) is widely used to evaluate brain edema in stroke research, the usefulness of brain weight is undetermined. In this study, we examined the role of brain weight in the evaluation of brain edema in experimental SAH. The endovascular perforation model of SAH was used, and rats were assessed by neurological scoring (NS). The brains were quickly removed at 24 h after the operation, and the weights of wet cerebrum (WWC) and dry cerebrum (WDC) were measured to determine the brain water content (BWC). The correlations of those values with each other and to body weight (BW) were then examined to reveal the significance of brain weight. The rats were assigned to sham-operated (n = 8) and SAH (n = 16) groups. There were no significant differences in WWC between the groups (p = 0.61). WWC was correlated with BWC but not with NS in all rats. In addition, WWC was clearly correlated with BW and WDC, which is thought to substitute for the original brain weight. From these results, we suggest that the measurement of brain weight as an evaluation of brain edema is limited and that BW and original brain volume can be confounding factors in evaluation.

Tissue inhibitor of metalloproteinase-3 knockout mice exhibit enhanced energy expenditure through thermogenesis.

Tissue inhibitors of metalloproteinases (TIMPs) regulate matrix metalloproteinase activity and maintain extracellular matrix homeostasis. Although TIMP-3 has multiple functions (e.g., apoptosis, inhibition of VEGF binding to VEGF receptor, and inhibition of TNFα converting enzyme), its roles in thermogenesis and metabolism, which influence energy expenditure and can lead to the development of metabolic disorders when dysregulated, are poorly understood. This study aimed to determine whether TIMP-3 is implicated in metabolism by analyzing TIMP-3 knockout (KO) mice. TIMP-3 KO mice had higher body temperature, oxygen consumption, and carbon dioxide production than wild-type (WT) mice, although there were no differences in food intake and locomotor activity. These results suggest that metabolism is enhanced in TIMP-3 KO mice. Real-time PCR analysis showed that the expression of PPAR-δ, UCP-2, NRF-1 and NRF-2 in soleus muscle, and PGC-1α and UCP-2 in gastrocnemius muscle, was higher in TIMP-3 KO mice than in WT mice, suggesting that TIMP-3 deficiency may increase mitochondrial activity. When exposed to cold for 8 hours to induce thermogenesis, TIMP-3 KO mice had a higher body temperature than WT mice. In the treadmill test, oxygen consumption and carbon dioxide production were higher in TIMP-3 KO mice both before and after starting exercise, and the difference was more pronounced after starting exercise. Our findings suggest that TIMP-3 KO mice exhibit enhanced metabolism, as reflected by a higher body temperature than WT mice, possibly due to increased mitochondrial activity. Given that TIMP-3 deficiency increases energy expenditure, TIMP-3 may present a novel therapeutic target for preventing metabolic disorders.