Effects of mild hypothermia on the ROS and expression of caspase-3 mRNA and LC3 of hippocampus nerve cells in rats after cardiopulmonary resuscitation

Lu, Jian; Shen, Yi; Qian, Hai-Yan; Liu, Lijun; Zhou, Baochun; Xiao, Yan; Mao, Jinning; An, Guoyin; Rui, Mingzhong; Wang, Tao; Zhu, Cheng

doi:10.5847/wjem.j.issn.1920-8642.2014.04.010

Cited by 22 publications

(14 citation statements)

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“…[37] There has been some evidence that temperature reduction might lessen the activation of these executioner caspases, [38][39][40] which is consistent with our results (Fig 5). Our data shows significantly reduced levels of both caspase 3 and 7 ( Fig 5) as long as TH is administered within the first 4 hours, leading to a clear benefit in maintaining high cell population viability.…”

Section: Discussionsupporting

confidence: 91%

Application of mild hypothermia successfully mitigates neural injury in a 3D in-vitro model of traumatic brain injury

et al. 2020

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Therapeutic hypothermia (TH) is an attractive target for mild traumatic brain injury (mTBI) treatment, yet significant gaps in our mechanistic understanding of TH, especially at the cellular level, remain and need to be addressed for significant forward progress to be made. Using a recently-established 3D in-vitro neural hydrogel model for mTBI we investigated the efficacy of TH after compressive impact injury and established critical treatment parameters including target cooling temperature, and time windows for application and maintenance of TH. Across four temperatures evaluated (31.5, 33, 35, and 37˚C), 33˚C was found to be most neuroprotective after 24 and 48 hours post-injury. Assessment of TH administration onset time and duration showed that TH should be administered within 4 hours post-injury and be maintained for at least 6 hours for achieving maximum viability. Cellular imaging showed TH reduced the percentage of cells positive for caspases 3/7 and increased the expression of calpastatin, an endogenous neuroprotectant. These findings provide significant new insight into the biological parameter space that renders TH effective in mitigating the deleterious effects of cellular mTBI and provides a quantitative foundation for the future development of animal and preclinical treatment protocols. OPEN ACCESSCitation: Scimone MT, Cramer HC, III, Hopkins P, Estrada JB, Franck C (2020) Application of mild hypothermia successfully mitigates neural injury in a 3D in-vitro model of traumatic brain injury. PLoS ONE 15(4): e0229520. https://doi.org/10.. Jonathan Estrada received a GAANN Fellowship from Brown University. No biochemical pathways involved in TBI. Because changes in thermal energy can regulate nearly every biological function, therapeutic hypothermia (TH) has been suggested as an attractive potential treatment option. Currently, TH, sometimes referred to as targeted temperature management, is used in some clinical procedures, such as cardiopulmonary bypass surgery or circulatory arrest but not in the treatment of TBI. [8] The documented benefits of TH in TBI studies include reduction of intracranial pressure, neuroexcitotoxicity, caspase enzyme activation, inflammation, cerebral edema, metabolic rate, and reactive oxygen species (ROS) generation.[9-13] Despite these potential advantages, there have been numerous studies that have resulted in neutral or unfavorable outcomes in clinical or preclinical TH treatment groups. [13][14][15] Complications of and from systemic, i.e., whole body, administration of hypothermia may include pneumonia, coagulopathy, and an increased risk of infection, among others. [9,13] Patients with TBI often have comorbid injuries, complicating treatment and outcome. Complex symptoms and treatments make TH for TBI a difficult problem to study in clinical settings. Clinical methods have not been consistent between studies, resulting in differences in hypothermia administration duration, onset time, cooling rate, method of cooling; as well as differences in inclusion criteria. [16,1...

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Section: Discussionsupporting

confidence: 91%

Application of mild hypothermia successfully mitigates neural injury in a 3D in-vitro model of traumatic brain injury

et al. 2020

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“…Autophagy is the primary mechanism by which cytosolic proteins and organelles are degraded (18). However, excessive autophagy activation in neurocytes damaged by I/R can lead to non-apoptotic cell death (19,20), which is called autoghagic programmed cell death. Beclin1 activates critical steps in autophagy, including the formation and maturation of autophagosomes (21,22).…”

Section: Introductionmentioning

confidence: 99%

Hypothermic properties of dexmedetomidine provide neuroprotection in rats following cerebral ischemia‑reperfusion injury

Liu

Zhu

et al. 2019

Exp Ther Med

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Dexmedetomidine (Dex) is a sedative and analgesic agent that is widely administered to patients admitted to the intensive care unit, and has been demonstrated to result in hypothermia. Many patients have been revealed to benefit from therapeutic hypothermia, which can mitigate cerebral ischemia/reperfusion (I/R) injury following successful cardiopulmonary resuscitation. However, studies investigating the efficacy of Dex in I/R treatment is lacking. The present study aimed to investigate the efficacy of Dex in mitigating neuronal damage, and to determine the possible mechanism of its effects in a rat model of cardiac arrest (CA). CA was induced in Sprague-Dawley rats by asphyxiation for 5 min. Following successful resuscitation, the surviving rats were randomly divided into two treatment groups; one group was intraperitoneally administered with Dex (D group), whereas the control group was treated with normal saline (N group). Critical parameters, including core temperature and blood pressure were monitored following return of spontaneous circulation (ROSC). Arterial blood samples were collected at 10 min after surgery (baseline) 30 and 120 min post-ROSC; and neurological deficit scores (NDS) of the rats were taken 12 or 24 h after ROSC prior to euthanasia. The hippocampal tissue was then removed for analysis by histology, electron microscopy and western blotting. Rats in the D group exhibited a lower core temperature and higher NDS scores compared with the N group (P<0.05). In addition, Dex injection resulted in reduced expression of apoptotic and autophagy-associated factors in the hippocampus (P<0.05). Dex treatment induced hypothermia and improved neurological function in rats after ROSC following resuscitation from CA by inhibiting neuronal apoptosis and reducing autophagy, which suggested that Dex may be a potential therapy option for patients with CA.

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“…It is related to both cell survival and cell death, and is cellular context‐dependent. Most recently, a plethora of evidence has indicated that autophagy is tightly associated with cancers, and that this has become a new therapeutic target in cancer treatment . Rapamycin‐induced autophagy in MCF‐7 breast cancer cells delayed the attendance of Rad51 and breast cancer 1 (BRCA1) in DSBs upon radiotherapy, leading to the accumulation of DSBs and cell death .…”

Section: Introductionmentioning

confidence: 99%

“…Most recently, a plethora of evidence has indicated that autophagy is tightly associated with cancers, and that this has become a new therapeutic target in cancer treatment. [10][11][12] Rapamycin-induced autophagy in MCF-7 breast cancer cells delayed the attendance of Rad51 and breast cancer 1 (BRCA1) in DSBs upon radiotherapy, leading to the accumulation of DSBs and cell death. 13 Similarly, the sensitivity of pancreatic carcinoma cell PC-2 to radiotherapy was significantly enhanced postrapamycin treatments, and the upregulation of autophagy mediator Beclin-1 sensitized lung cancer cells to irradiation.…”

Section: Introductionmentioning

confidence: 99%

Rapamycin‐induced autophagy sensitizes A549 cells to radiation associated with DNA damage repair inhibition

Liu

Wang

et al. 2016

Thoracic Cancer

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BackgroundAutophagy has been reported to increase in cancer cells after radiation. However, it remains unknown whether increased autophagy as a result of radiation affects DNA damage repair and sensitizes cancer cells. In this study, the radiosensitization effect of rapamycin, a mammalian target of rapamycin inhibitor that induces autophagy, on human lung adenocarcinoma A549 cells was investigated.MethodsA549 cells were treated with different concentrations of rapamycin. Cell viability was evaluated by methyl‐thiazolyl‐tetrazolium assay. Survival fraction values of A549 cells after radiotherapy were detected by colony formation assay. Autophagosome was observed by a transmission electron microscope. Furthermore, Western blot was employed to examine alterations in autophagy protein LC3 and p62, DNA damage protein γ–H2AX, and DNA damage repair proteins Rad51, Ku70, and Ku80. Rad51, Ku70, and Ku80 messenger ribonucleic acid (mRNA) expression levels were examined by real‐time polymerase chain reaction.ResultsRapamycin suppressed A549 cell proliferation in dose and time‐dependent manners. An inhibitory concentration (IC) 10 dose of rapamycin could induce autophagy in A549 cells. Rapamycin combined with radiation significantly decreased the colony forming ability of cells, compared with rapamycin or radiation alone. Rapamycin and radiation combined increased γ–H2AX expression levels and decreased Rad51 and Ku80 expression levels, compared with single regimens. However, rapamycin treatment did not induce any change in Rad51, Ku70, and Ku80 mRNA levels, regardless of radiation.ConclusionsThese findings indicate that increasing autophagy sensitizes lung cancer cells to radiation.

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Effects of mild hypothermia on the ROS and expression of caspase-3 mRNA and LC3 of hippocampus nerve cells in rats after cardiopulmonary resuscitation

Cited by 22 publications

References 14 publications

Application of mild hypothermia successfully mitigates neural injury in a 3D in-vitro model of traumatic brain injury

Application of mild hypothermia successfully mitigates neural injury in a 3D in-vitro model of traumatic brain injury

Hypothermic properties of dexmedetomidine provide neuroprotection in rats following cerebral ischemia‑reperfusion injury

Rapamycin‐induced autophagy sensitizes A549 cells to radiation associated with DNA damage repair inhibition

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