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Dantrolene enhances the protective effect of hypothermia on cerebral cortex neurons.

Xu SY, Hu FY, Ren LJ, Chen L, Zhou ZQ, Zhang XJ, Li WP - Neural Regen Res (2015)

Bottom Line: Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis.Furthermore, improvements in cell morphology were observed.The combined treatment enhanced these responses compared with either treatment alone.

View Article: PubMed Central - PubMed

Affiliation: Postdoctoral Workstation, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China ; Department of Brain Center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University First Affiliated Hospital, Shenzhen, Guangdong Province, China.

ABSTRACT
Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia (at 33°C), or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.

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Related in: MedlinePlus

Effects of hypothermia plus dantrolene on the morphology of OGD/R cells.Phase-contrast microscopy of (A) normal group; (B) OGD/R group in which OGD/R induces injury, observed as neuronal loss, axonal rupture, and network connection fracture; (C) hypothermia group; (D) dantrolene group in which hypothermia or dantrolene treatment ameliorates the morphological abnormality; (E) hypothermia + dantrolene group in which the combined treatment enhances neuroprotection compared to either treatment alone. Scale bars: 50 μm. OGD/R: Oxygen-glucose deprivation/reoxygenation.
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Figure 4: Effects of hypothermia plus dantrolene on the morphology of OGD/R cells.Phase-contrast microscopy of (A) normal group; (B) OGD/R group in which OGD/R induces injury, observed as neuronal loss, axonal rupture, and network connection fracture; (C) hypothermia group; (D) dantrolene group in which hypothermia or dantrolene treatment ameliorates the morphological abnormality; (E) hypothermia + dantrolene group in which the combined treatment enhances neuroprotection compared to either treatment alone. Scale bars: 50 μm. OGD/R: Oxygen-glucose deprivation/reoxygenation.

Mentions: Cell bodies of the normal group (Figure 4A) showed stereoscopic perception and strong refractivity. After OGD and reoxygenation (OGD/R) injury, the neuronal density was reduced. In addition, neurite extension was fractured and unable to form network connections (Figure 4B). Hypothermia and dantrolene treatment alone ameliorated OGD/R-induced morphological changes (Figure 4C, D). Their combined treatment enhanced neuroprotection compared with each treatment alone (Figure 4E).


Dantrolene enhances the protective effect of hypothermia on cerebral cortex neurons.

Xu SY, Hu FY, Ren LJ, Chen L, Zhou ZQ, Zhang XJ, Li WP - Neural Regen Res (2015)

Effects of hypothermia plus dantrolene on the morphology of OGD/R cells.Phase-contrast microscopy of (A) normal group; (B) OGD/R group in which OGD/R induces injury, observed as neuronal loss, axonal rupture, and network connection fracture; (C) hypothermia group; (D) dantrolene group in which hypothermia or dantrolene treatment ameliorates the morphological abnormality; (E) hypothermia + dantrolene group in which the combined treatment enhances neuroprotection compared to either treatment alone. Scale bars: 50 μm. OGD/R: Oxygen-glucose deprivation/reoxygenation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590241&req=5

Figure 4: Effects of hypothermia plus dantrolene on the morphology of OGD/R cells.Phase-contrast microscopy of (A) normal group; (B) OGD/R group in which OGD/R induces injury, observed as neuronal loss, axonal rupture, and network connection fracture; (C) hypothermia group; (D) dantrolene group in which hypothermia or dantrolene treatment ameliorates the morphological abnormality; (E) hypothermia + dantrolene group in which the combined treatment enhances neuroprotection compared to either treatment alone. Scale bars: 50 μm. OGD/R: Oxygen-glucose deprivation/reoxygenation.
Mentions: Cell bodies of the normal group (Figure 4A) showed stereoscopic perception and strong refractivity. After OGD and reoxygenation (OGD/R) injury, the neuronal density was reduced. In addition, neurite extension was fractured and unable to form network connections (Figure 4B). Hypothermia and dantrolene treatment alone ameliorated OGD/R-induced morphological changes (Figure 4C, D). Their combined treatment enhanced neuroprotection compared with each treatment alone (Figure 4E).

Bottom Line: Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis.Furthermore, improvements in cell morphology were observed.The combined treatment enhanced these responses compared with either treatment alone.

View Article: PubMed Central - PubMed

Affiliation: Postdoctoral Workstation, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China ; Department of Brain Center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University First Affiliated Hospital, Shenzhen, Guangdong Province, China.

ABSTRACT
Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia (at 33°C), or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.

No MeSH data available.


Related in: MedlinePlus