Table 1 Characteristics and main findings of relevant studies reporting on cerebral injury
From: Protective effects of dexmedetomidine in vital organ injury: crucial roles of autophagy
Study/ref. | Experimental model | Types of injury | DEX administration | Status of autophagy | Associated genes or pathways | Main findings |
|---|---|---|---|---|---|---|
Luo et al. 2017 [27] | Mouse | Ischemic cerebral injury | Intraperitoneally, 25 μg/kg | Inhibited | Upregulating HIF-1α | Postconditioning with DEX at beginning of reperfusion protects mouse brain from ischemia–reperfusion injury via inhibition of neuronal autophagy by upregulating of Bcl-1, p62, and HIF-1α and downregulating of LC3 and Beclin 1 |
Shen et al. 2017 [42] | Rat | Traumatic brain injury | Injected via the left femoral vein, 15 μg/kg | Inhibited | Activation of the PI3K/Akt/ mTOR pathway | DEX alleviates the degree of traumatic brain injury via inhibition of neuronic autophagy by activating PI3K/AKT/mTOR signaling pathway |
Shan et al. 2018 [43] | Pregnant rat | Neurological injury | Intraperitoneally, 20 μg/kg | Inhibited | Upregulating Bcl2, downregulating Drp1 and Bax | DEX improved the abnormal morphology of hippocampal CA1 regions of rat-pup brains and inhibited sevoflurane-induced activation of autophagy |
Yi et al. 2018 [44] | Rat | Cognitive impairment | Intraperitoneally, 4 μg/kg | Inhibited | Downregulating of LC3-I, LC3-II, and Beclin-1 | DEX improved the cognitive dysfunction in aged rats under sevoflurane anesthesia by decreasing autophagy of hippocampal neurons |
Lu et al. 2019 [45] | Rat | Cerebral ischemia‑reperfusion injury | Intraperitoneally, 50 μg/kg | Inhibited | Downregulation of Bax and Caspase-3, upregulation in Bcl‑2 and HSP70 | DEX exerts neuroprotective effect by inducing mild hypothermia, slowing down heart rate, attenuating apoptosis of neurocytes, and repressing autophagy |
Zhu et al. 2019 [46] | Rat | Cerebral ischemia/reperfusion injury | Left femoral vein, 3 μg/kg | Inhibited | Inhibiting the activation of JNK signaling pathway | The effect of DEX might be related to the inhibition of JNK pathway activation, and to affect the expressions of inflammatory factors and autophagy-related proteins |
Tang et al. 2019 [47] | SH-SY5Y cells | Ischemia/reperfusion cerebral injury | Treated with 1 μM DEX for 18 h reoxygenation | Inhibited | Downregulating LC3 and Beclin 1, upregulating BCL-2, p62, and TOM20 | DEX increased the cell survival meanwhile reduced the production of autophagic vesicles, as well as regulated some related proteins |
Li et al. 2020 [50] | Rat | Traumatic brain injury | Intraperitoneally, 20 μg/kg | Inhibited | Inactivation of the circLrp1b/miR-27a-3p/Dram2 signaling pathway | DEX inhibits inflammatory response and autophagy in a traumatic brain injury rat model by acting on the circLrp1b/miR-27a-3p/Dram2 pathway |
Yu et al. 2020 [21] | Rat | Hippocampus injury | Intraperitoneally, 25 μg/kg | Activated mitophagy | Increased expression levels of FOXO3α, BINP3, LC3-II/LC3-I, and P62 | DEX attenuated hippocampus injury and improved cognitive function by activating SIRT3-mediated mitophagy and inhibiting activation of the NLRP3 inflammasome |
Zhu et al. 2020 [48] | Mouse and astrocytes | Cerebral ischemia | 1 μM, via medium | Activated astrocytes autophagy | Upregulating TSC2 and 4EBP1, downregulating mTOR | DEX increases the viability and inhibits apoptosis of astrocytes exposed to oxygen–glucose deprivation, which might be related to the activation of autophagy by regulating TSC2/mTOR pathway |
Hu et al. 2020 [49] | PC12 Cells | OGD/R injury | 1 μg/mL, via medium | Inhibited | Decreasing the levels of STIM1 and Orai1 proteins | DEX attenuates cell apoptosis following OGD/R by inhibiting autophagy in PC12 cells, which may be correlated to the repression of Ca2+-STIM1/Orai1 signaling |
Zhu et al. 2021 [52] | Rat | Cerebral ischemia/reperfusion | Caudal vein, 3 µg/kg/h | Inhibited | Inhibiting the expression of miR‑199a | DEX inhibited autophagy and decreased nerve cell injury by decreasing the level of miR‑199a |
Xue et al. 2021 [51] | Rat | Neonatal hypoxic ischemia | Intraperitoneally, 25 μg/kg | Inhibited | Down-regulating LC3B-II and Beclin 1 | Protective effects of DEX were evidenced by the inhibition of excessive autophagy of neurons and microglia, reducing the decline of long-term neuronal density and axon demyelination |
Feng et al. 2021 [53] | Mouse | Traumatic brain injury | Intraperitoneally, 20 μg/kg | Inhibited | Decreasing the levels of ROS and MDA, and increasing the expression of Nrf2 and HO‑1 | DEX improves neurological outcomes and reduces neuronal death by protecting against neural autophagy and neuroinflammation by regulating the ROS/Nrf2 pathway |