The neuroprotective effect of dexmedetomidine and its mechanism

Hu, Yijun; Zhou, Hong; Zhang, Huanxin; Sui, Yunlong; Zhang, Zhen; Zou, Yuntao; Li, Kunquan; Zhao, Yunyi; Xie, Jiping; Zhang, Lunzhong

doi:10.3389/fphar.2022.965661

Cited by 32 publications

(16 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mechanistic studies have clearly demonstrated that DEX serves a variety of signaling pathways. When examined further, DEX is often involved in signaling pathways that are activated under oxidative stress and triggered by various stressors [ 127 ]. Additionally, what is worth mentioning are microRNAs (miRNAs), which play an important role in post-transcriptional gene regulation [ 128 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Dexmedetomidine against Hyperoxia-Damaged Cerebellar Neurodevelopment in the Juvenile Rat

et al. 2023

View full text Add to dashboard Cite

Impaired cerebellar development of premature infants and the associated impairment of cerebellar functions in cognitive development could be crucial factors for neurodevelopmental disorders. Anesthetic- and hyperoxia-induced neurotoxicity of the immature brain can lead to learning and behavioral disorders. Dexmedetomidine (DEX), which is associated with neuroprotective properties, is increasingly being studied for off-label use in the NICU. For this purpose, six-day-old Wistar rats (P6) were exposed to hyperoxia (80% O2) or normoxia (21% O2) for 24 h after DEX (5 µg/kg, i.p.) or vehicle (0.9% NaCl) application. An initial detection in the immature rat cerebellum was performed after the termination of hyperoxia at P7 and then after recovery in room air at P9, P11, and P14. Hyperoxia reduced the proportion of Calb1+-Purkinje cells and affected the dendrite length at P7 and/or P9/P11. Proliferating Pax6+-granule progenitors remained reduced after hyperoxia and until P14. The expression of neurotrophins and neuronal transcription factors/markers of proliferation, migration, and survival were also reduced by oxidative stress in different manners. DEX demonstrated protective effects on hyperoxia-injured Purkinje cells, and DEX without hyperoxia modulated neuronal transcription in the short term without any effects at the cellular level. DEX protects hyperoxia-damaged Purkinje cells and appears to differentially affect cerebral granular cell neurogenesis following oxidative stress.

show abstract

Section: Discussionmentioning

confidence: 99%

Protective Effect of Dexmedetomidine against Hyperoxia-Damaged Cerebellar Neurodevelopment in the Juvenile Rat

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Some other studies have shown that M1 type of macrophages rely on glycolysis to generate energy, while M2 type produces ATP through the tricarboxylic acid cycle [29,30], which corresponds to the pathway of energy provision under stress-and steady-state. α 2 -AR is widely distributed in central nervous system and peripheral tissues, such organ protective effects of Dex have been detected in brain [31], heart [32] and lung [33] injury. Likewise, our previous experiments found that excitation of α 2 -AR exhibits cytoprotective effects on human renal tubular epithelial cells [15] and pulmonary microvascular Endothelial cells [17] including activating intracellular focal adhesion kinase (FAK) and PI3K/Akt pathway, which increase Akt phosphorylation [18,34].…”

Section: Discussionmentioning

confidence: 99%

Alveolar macrophages polarity switch via α 2 -adrenoceptor activation ameliorates pulmonary inflammation following kidney ischemia reperfusion

Qin

He³

et al. 2023

Preprint

View full text Add to dashboard Cite

Purpose: To investigate the anti-inflammatory mechanism of dexmedetomidine (Dex), an α2-adrenoceptor (α2-AR) agonist, on renal ischemia-reperfusion (RIR)-induced acute lung injury (ALI). Methods: RIR was performed in C57BL/6J mice by bilateral renal pedicles occlusion for 60min and reperfusion for 24h. Mice were pre-treated with or without Dex alone or combined atipamezole (Atip), an α2-AR antagonist. The pulmonary histopathological evaluation, arterial blood gas analysis, cell count and multiple cytokines examination in BALF, global inflammation status assessment in lung tissue and alveolar macrophages phenotype investigation were accomplished. In vitro, the polarity of mice alveolar macrophages (MH-S) treated with serum from normal or RIR mice were indirectly detected by qPCR. Results: The results indicated that, compared to RIR animal, dexmedetomidine reduced lung injury and significantly promoted macrophage polarization towards an anti-inflammatory M2 phenotype in the pulmonary tissue. Meanwhile, the reduction of inflammatory cell infiltration and pro-inflammatory cytokines levels were observed. In vitro studies confirmed that dexmedetomidine skewed MH-S towards M2 phenotype after stimulation of RIR serum. After administration of the atipamezole, these above effects were abolished. Conclusion: Dexmedetomidine ameliorates renal ischemia-reperfusion induced ALI through activation of α2-adrenoceptor to skew macrophages towards an anti-inflammatory phenotype to reduce pulmonary global inflammation.

show abstract

“…The possible neuropharmacological mechanisms of action of the rapamycin and axitinib synergy should note. Thus, rapamycin reduces the production of HIF-1α [20,21] and abolishes insulin-induced HIF-1 activation in retinal pigment epithelial cells [22]. Hence, mTOR upstream is considered a way of HIF-1α activation and HIF-1-dependent gene expression [20].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical neuroinflammatory markers in the hippocampus of PTZ-kindled rats under conditions of rapamycin and axitinib treatment

Poshyvak

Pinyazhko

Godlevsky

et al. 2023

SR: PS

View full text Add to dashboard Cite

The aim of the study is to determine the level of HIF-1α, TNF-α, and NF-kB in the hippocampus of kindled rats treated with rapamycin and axitinib. Materials and methods. Kindling was produced in 29 rats by administration of three-week pentylenetetrazole (PTZ, 35.0 mg/kg, i.p.). Treatment with rapamycin (0.5 mg/kg, i.p.) and axitinib (2.5 mg/kg, i.p.) was performed for ten days in fully kindled rats. The avidin-biotin-peroxidase method was used for hippocampal slice staining. For negative control, staining was performed using only secondary antibodies. Results. The HIF-1α expression increased in kindled rats raised by 1.77 times compared to the control (p<0.001). Axitinib treatment resulted in of HIF-1α level of 16.7 % (p<0.05) compared with kindled animals, while combined treatment with rapamycin and axitinib reduced HIF-1α by 33.8 % (p<0.01). In kindled rats, TNF-α expression was 3.74 times greater than in control (p<0.001). Rapamycin treatment reduced TNF-α by 31.0 % (p<0.01). Axitinib treatment caused a reduction of TNF-α by 21.1 % (p<0.05). Combined treatment with rapamycin and axitinib reduced TNF-α by 48.0 % (p<0.001) but still exceeded the TNF-α in control by 1.95 times (p<0.01). NF-kB level in kindled rats exceeded the control by three times (p<0.001). Rapamycin caused a reduction of 19.3 % (p>0.05), while axitinib – by 26.5 % (p<0.05) compared with kindled rats. Combined treatment with rapamycin and axitinib resulted in NF-kB reduction by 56.7 % compared with kindled rats (p<0.001). Conclusions. PTZ-kindling resulted in an increase in the immunoreactivity of HIF-1α, TNF-α, and NF-kB in the hippocampus. Combined treatment with rapamycin and axitinib engendered prevention of generalized seizures and normalized the level of HIF-1α and NF-kB with a significant reduction of TNF-α. Effects of treatment favours of synergy action of rapamycin and axitinib

show abstract

The neuroprotective effect of dexmedetomidine and its mechanism

Cited by 32 publications

References 113 publications

Protective Effect of Dexmedetomidine against Hyperoxia-Damaged Cerebellar Neurodevelopment in the Juvenile Rat

Protective Effect of Dexmedetomidine against Hyperoxia-Damaged Cerebellar Neurodevelopment in the Juvenile Rat

Alveolar macrophages polarity switch via α 2 -adrenoceptor activation ameliorates pulmonary inflammation following kidney ischemia reperfusion

Immunohistochemical neuroinflammatory markers in the hippocampus of PTZ-kindled rats under conditions of rapamycin and axitinib treatment

Contact Info

Product

Resources

About