RESUMO
Objective To explore the cellular localization of chemokine (C-X-C motif) ligand 1 (CXCL1) in brain tissue and its expres-sion in brain tissue and blood in patients with severe traumatic brain injury (TBI), as well as its correlation with the injury severity. Methods From September, 2013 to October, 2015, 78 cases of TBI with craniotomy admitted to our hospital were involved as TBI group. A total of 78 peripheral blood samples and 19 brain tissue samples were studied. According to the scores of Glasgow Coma Scale (GCS) at admission, the TBI group was classified as severe TBI group (6~8, n=35) and particularly severe TBI group (3~5, n=43). Ten cases of control brain tissue were taken from patients with cerebral aneurysms or benign tumor and also undergoing craniotomy during the same time. Peripheral blood from ten healthy people were involved as the healthy control group. Immunofluorescent double staining was used to detect the cellular local-ization of CXCL1 in brain tissues, and ELISA was used to detect the expression of CXCL1 in brain tissue and blood. The relationship be-tween the level of CXCL1 in peripheral blood at different time and the score of Glasgow Outcome Scale (GOS) was analyzed with Spear-man correlation analysis. Results In normal brain tissue, CXCL1 mainly localized in astrocytes. For severe TBI, CXCL1 mainly expressed in neurons and astrocytes. The level of CXCL1 was higher in brain tissue in the particularly severe TBI group than in the severe TBI group (t=-12.58, P0.05). In the particularly severe TBI group, the level of CXCL1 in blood reached a peak before and one day after surgery, then gradually decreased, and was still higher than that in the healthy control group 30 days after surgery (P<0.05). The level of CXCL1 in blood was higher in the particularly severe TBI group than in the severe TBI group at all time points (P<0.05), and the level before surgery was negatively correlated with the score of GOS in the particularly severe TBI group (r=-0.351, P<0.05). Conclusion The CXCL1 protein of injury brain tissue was mainly colocalized in neurons and astrocytes in severe TBI patients, and the ex-pression was associated with injury severity and outcome.
RESUMO
In patients with advanced cancer, cancer-induced bone pain (CIBP) is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase (JNK) and chemokine (C-X-C motif) ligand 1 (CXCL1) have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1 (pJNK1) and pJNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective pJNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the pJNK/CXCL1 pathway may provide a new choice for treatment of CIBP.