A novel small-molecular CCR5 antagonist promotes neural repair after stroke

Wu, Qinglin; Cui, Lianxian; Ma, Wen-Yu; Wang, Shasha; Zhang, Zhao; Feng, Zhong‐Ping; Sun, Hong‐Shuo; Chu, Shifeng; Wang, He; Chen, Nai‐Hong

doi:10.1038/s41401-023-01100-y

Cited by 13 publications

(5 citation statements)

References 34 publications

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“…Specifically, when brain tissue suffered from ischemia/reperfusion injury, the expression of CKLF1 in BV2 microglia was increased, and increased CKLF1 induced the polarization of BV2 microglia to the M1 phenotype and induced the process of inflammatory response (Chen et al., 2019 ). Reportedly, CKLF1 role in ischemic stroke may be reflected in increased blood–brain barrier disruption (Kong et al., 2016 ; Wu et al., 2023 ). After injecting CKLF1 antibody into the right encephalocele of cerebral ischemic rats, brain water content was decreased, expressions of aquaporin‐4 and matrix metalloproteinase‐9 were depressed, and expressions of zonula occludens‐1 and occludin were increased significantly, suggesting that CKLF1 may be involved in the destruction of blood–brain barrier after ischemia/reperfusion in cerebral ischemic rats (Kong et al., 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Utility of serum chemokine–like factor 1 as a biomarker of severity and prognosis after severe traumatic brain injury: A prospective observational study

Wu,

Su,

Tian

et al. 2024

Brain and Behavior

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BackgroundChemokine‐like factor 1 (CKLF1) may be involved in the inflammatory response and secondary brain injury after severe traumatic brain injury (sTBI). We determined serum CKLF1 levels of sTBI patients to further investigate the correlation of CKLF1 levels with disease severity, functional prognosis, and 180‐day mortality of sTBI.MethodsSerum CKLF1 levels were measured at admission in 119 sTBI patients and at entry into study in 119 healthy controls. Serum CKLF levels of 50 patients were also quantified at days 1–3, 5, and 7 after admission. Glasgow coma scale (GCS) scores and Rotterdam computerized tomography (CT) classification were utilized to assess disease severity. Extended Glasgow outcome scale (GOSE) scores were recorded to evaluate function prognosis at 180 days after sTBI. Relations of serum CKLF1 levels to 180‐day poor prognosis (GOSE scores of 1–4) and 180‐day mortality were analyzed using univariate analysis, followed by multivariate analysis. Receiver‐operating characteristic (ROC) curve was built to investigate prognostic predictive capability.ResultsSerum CKLF1 levels of sTBI patients increased at admission, peaked at day 2, and then gradually decreased; they were significantly higher during the 7 days after sTBI than in healthy controls. Differences of areas under ROC curve (areas under the curve [AUCs]) were not significant among the six time points. Multivariate analysis showed that serum CKLF1 levels were independently correlated with GCS scores, Rotterdam CT classification, and GOSE scores. Serum CKLF1 levels were significantly higher in non‐survivors than in survivors and in poor prognosis patients than in good prognosis patients. Serum CKLF1 levels independently predicted 180‐day poor prognosis and 180‐day mortality, and had high 180‐day prognosis and mortality predictive abilities, and their AUCs were similar to those of GCS scores and Rotterdam CT classification. Combination model containing serum CKLF1, GCS scores, and Rotterdam CT classification performed more efficiently than any of them alone in predicting mortality and poor prognosis. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve.ConclusionSerum CKLF1 levels are significantly associated with disease severity, poor 180‐day prognosis, and 180‐day mortality in sTBI patients. Hence, complement CKLF1 may serve as a potential prognostic biomarker of sTBI.

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Section: Discussionmentioning

confidence: 99%

Utility of serum chemokine–like factor 1 as a biomarker of severity and prognosis after severe traumatic brain injury: A prospective observational study

Wu,

Su,

Tian

et al. 2024

Brain and Behavior

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“…Additionally, the chemokines whose algesic effects have been confirmed in behavioral studies in mice/rats are marked with a red border. Scheme created based on data from the following literature [39][40][41]48,53,65,66,[70][71][72][73]80,85,86,89,90,92,100,132,[139][140][141][142][143][144][145][146][147][148][149][150][151][152][153]164,203,[222][223][224][225][226][227][229][230][231][232][233][234][235]…”

Section: Discussionmentioning

confidence: 99%

“…By selectively binding to the CCR5 receptor, maraviroc prevents CCR5-tropic entering the cell by HIV-1 viruses [413]. However, in animal studies after CNS injury, it has been shown that maraviroc produces neuroprotective effects in TBI [232,233], FCS [234], CIBI [235], and ICH [236] models. Moreover in neuropathy models, it is able not only to diminish pain but enhance opioid effectiveness [71,85,237].…”

Section: Discussionmentioning

confidence: 99%

“…Literature data clearly indicate that CCR5 plays an important role in recovery after brain injury of different etiologies (please see Table 1) [75,[232][233][234][235][236]238,345]. Poststroke neuronal knockdown of CCR5 in the motor cortex led to the early recovery of motor control in mice [345].…”

Section: Ccr5-pharmacological Modulationmentioning

confidence: 99%

“…TBI [222,223]; LDH [197] CCI [48,224]; LAMNT [225] CCX872 TBI [226] ND Maraviroc TBI [232,233]; FCS [234]; CIBI [235]; ICH […”

Section: Rs504393mentioning

confidence: 99%

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CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

Ciechanowska,

Mika

2024

IJMS

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Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis. This suggests that there are opportunities for similar pharmacological therapeutic interventions in the damage of various etiologies. Experimental data indicate that after CNS/PNS damage, the levels of 16 among the 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, and CCL22, increase in the brain and/or spinal cord and have strong proinflammatory and/or pronociceptive effects. According to the available literature data, further investigation is still needed for understanding the role of the remaining chemokines, especially six of them which were found in humans but not in mice/rats, i.e., CCL13, CCL14, CCL15, CCL16, CCL18, and CCL23. Over the past several years, the results of studies in which available pharmacological tools were used indicated that blocking individual receptors, e.g., CCR1 (J113863 and BX513), CCR2 (RS504393, CCX872, INCB3344, and AZ889), CCR3 (SB328437), CCR4 (C021 and AZD-2098), and CCR5 (maraviroc, AZD-5672, and TAK-220), has beneficial effects after damage to both the CNS and PNS. Recently, experimental data have proved that blockades exerted by double antagonists CCR1/3 (UCB 35625) and CCR2/5 (cenicriviroc) have very good anti-inflammatory and antinociceptive effects. In addition, both single (J113863, RS504393, SB328437, C021, and maraviroc) and dual (cenicriviroc) chemokine receptor antagonists enhanced the analgesic effect of opioid drugs. This review will display the evidence that a multidirectional strategy based on the modulation of neuronal–glial–immune interactions can significantly improve the health of patients after CNS and PNS damage by changing the activity of chemokines belonging to the CC family. Moreover, in the case of pain, the combined administration of such antagonists with opioid drugs could reduce therapeutic doses and minimize the risk of complications.

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