Synergistic effect of mild hypothermia and the Notch inhibitor DAPT against post stroke seizures

Yang, Guoshuai; Zhou, Xiaoyan; An, Xue-Fang; Liu, Xuan-Jun; Zhang, Yanjun; Yu, Dan

doi:10.1016/j.biopha.2017.10.036

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…Combined therapy with phenothiazines and MH also enhanced neuroprotection in ischemic rats through regulating the PI3K/Akt pathway (20). It has also been reported that the Notch inhibitor DAPT combined with MH exerted a synergistic effect on post-stroke seizures (21). It was reported that MH in combination with phenothiazine drugs achieved a better long-term motor performance after acute stroke (22).…”

Section: Discussionmentioning

confidence: 97%

Protective effects of combined treatment with mild hypothermia and edaravone against cerebral ischemia/reperfusion injury via oxidative stress and Nrf2 pathway regulation

Wang

et al. 2020

Int J Oncol

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Mild hypothermia (MH) and edaravone (EDA) exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury through activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. However, whether MH and EDA exert synergistic effects against cerebral I/R injury remains unknown. The aim of the present study was to investigate the effects and mechanism of action of MH in combination with EDA in cerebral I/R injury. A rat cerebral I/R injury model was constructed by middle cerebral artery occlusion (MCAO) followed by reperfusion, and the mice were treated by MH, EDA or the inhibitor of the Nrf2 signaling pathway brusatol (Bru). It was observed that mice treated by MCAO had higher neurological deficit scores and oxidative stress levels, and low spatial learning and memory capacity; moreover, the CA1 region of the hippocampi of the mice exhibited reduced neuronal density and viability, and reduced mitochondrial dysfunction. However, MH in combination with EDA reversed the effects of MCAO, which were blocked by Bru injection. The levels of glutathione (GSH), GSH peroxidase, catalase and superoxide dismutase in rat ischemic hemisphere tissues were reduced by Bru. Western blotting demonstrated that the combined treatment with MH and EDA promoted the nuclear localization of Nrf2, and increased the levels of NAD(P)H quinone oxidoreductase and heme oxygenase (HO)-1. In conclusion, MH combined with EDA exerted synergistic neuroprotective effects against cerebral I/R injury involving changes in the Nrf2/HO-1 pathway.

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Section: Discussionmentioning

confidence: 97%

Protective effects of combined treatment with mild hypothermia and edaravone against cerebral ischemia/reperfusion injury via oxidative stress and Nrf2 pathway regulation

Wang

et al. 2020

Int J Oncol

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“…After NICD is released from the cell membrane, it enters the nucleus and activates the RBP-Jk and Hes-1 factors in the downstream of the pathway, thereby promoting the expression of cell metabolism-related genes, which in turn regulate cell proliferation, differentiation, synaptic plasticity and neuronal aging. It plays an important role in the process of cell growth and development (Yang et al, 2017a).…”

Section: Discussionmentioning

confidence: 99%

Effect of Puerarin on EBI after SAH

Zeng

Kong

et al. 2022

Food Sci. Technol

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Objective: The neuroinflammatory reaction activated after the activation of microglia plays a critical role in the pathological mechanism of early brain injury after subarachnoid hemorrhage. The inhibitory effect of Puerarin on inflammatory response plays a protective effect against various diseases. The present study mainly explored whether Puerarin alleviates the inflammation after SAH by inhibiting the Notchl pathway. Methods: Rat SAH model was induced by internal carotid artery puncture. The content of brain edema was evaluated and assessed. Evans blue staining was used to detect the degree of blood-brain barrier damage. FJC staining was used to assess neuronal apoptosis. Western blot method was employed to detect the expressions of Notchl receptor and downstream factors to clarify the protective effect and specific mechanism of Puerarin on brain tissue after SAH. Results: Puerarin can attenuate the brain edema and blood-brain barrier damage caused by early brain injury within 72 h after SAH, reduce the contents of Ibal and CD68 positive microglia. Intraventricular injection of Notchl receptor blockers and Notchl siRNA can inhibit the activation of Notchl pathway after SAH, mitigate brain tissue edema, blood-brain barrier damage, and neuronal apoptosis, as well as inhibit the activation of microglia and the release of inflammatory factors. Puerarin can inhibit the activation of Notchl receptor and downstream pathways, and simultaneously increase the content of Botch in brain tissue. Conclusion: Puerarin can inhibit the activation of Notchl receptor through Botch factor, thereby inhibiting the neuroinflammatory reaction mediated by Notchl pathway, and finally improve the early neurological dysfunction after SAH.

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“…The risk of neurodegenerative diseases and poststroke depression is greatly increased after cerebral ischemia. For example, at least one-third of stroke survivors suffer from depression [ 76 ]; the long-term consequences of forebrain ischemia include delayed Parkinson's syndrome [ 77 ]; further, seizure is a serious complication of stroke, indicating poor prognosis [ 78 ]. A major criticism of preclinical stroke studies is that they tend to focus too narrowly on histological reduction of acute infarct volume.…”

Section: Ischemic Postconditioning May Improve Long-term Neurologimentioning

confidence: 99%

“…Glutamate acts in important excitatory neurotransmission in the CNS, while γ -aminobutyric acid (GABA) acts in inhibitory neurotransmission. The Glu/GABA imbalance is an important inducing factor of several CNS diseases such as Parkinson's disease and seizures [ 77 , 78 ]. An important enzyme regulating the balance of Glu/GABA is Glu decarboxylase (GAD).…”

Section: Ischemic Postconditioning May Improve Long-term Neurologimentioning

confidence: 99%

Cerebral Ischemic Postconditioning Plays a Neuroprotective Role through Regulation of Central and Peripheral Glutamate

You

Feng

Xin

et al. 2018

BioMed Research International

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Following cerebral ischemia/reperfusion (I/R) injury, a series of pathophysiological processes are stimulated in both the central nervous system (CNS) and the periphery, including, but not limited to, the peripheral immune and endocrine systems and underregulation of the neuroendocrine-immune network. Glutamate (Glu) is an important excitatory neurotransmitter in the CNS; its excitotoxicity following cerebral ischemia has been a focus of study for several decades. In addition, as a novel immunoregulator, Glu also regulates immune activity in both the CNS and periphery and may connect the CNS and periphery through regulation of the neuroendocrine-immune network. Ischemic postconditioning (IPostC) is powerful and activates various endogenous neuroprotective mechanisms following cerebral I/R, but only a few studies have focused on the mechanisms associated with Glu to date. Given that Glu plays an important and complex pathophysiological role, the understanding of Glu-related mechanisms of IPostC is an interesting area of research, which we review here.

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Synergistic effect of mild hypothermia and the Notch inhibitor DAPT against post stroke seizures

Cited by 5 publications

References 24 publications

Protective effects of combined treatment with mild hypothermia and edaravone against cerebral ischemia/reperfusion injury via oxidative stress and Nrf2 pathway regulation

Protective effects of combined treatment with mild hypothermia and edaravone against cerebral ischemia/reperfusion injury via oxidative stress and Nrf2 pathway regulation

Effect of Puerarin on EBI after SAH

Cerebral Ischemic Postconditioning Plays a Neuroprotective Role through Regulation of Central and Peripheral Glutamate

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