A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice

Choi, Ko-Eun; Hall, Casey D. Xavier; Sun, Jiayi; Wei, Ling; Mohamad, Osama; Dix, Thomas A.; Yu, Shan Ping

doi:10.1096/fj.11-201822

Cited by 88 publications

(132 citation statements)

References 68 publications

Supporting

Mentioning

127

Contrasting

Order By: Relevance

“…For infarct volume measurement, animals were sacrificed 24 hours after transplantation and their brains were removed and placed in a coronal brain matrix. Brains were sliced into 1-mm-thick sections, and infarct volume was determined using 2,3,5-triphenyltetrazolium chloride staining as detailed in [27].…”

Section: Stroke Model Cell Transplantation and Measurement Of Cell mentioning

confidence: 99%

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

et al. 2012

Self Cite

View full text Add to dashboard Cite

Various growth factor cocktails have been used to proliferate and then differentiate human neural progenitor (NP) cells derived from embryonic stem cells (ESC) for in vitro and in vivo studies. However, the cytokine leukemia inhibitory factor (LIF) has been largely overlooked. Here, we demonstrate that LIF significantly enhanced in vitro survival and promoted differentiation of human ESC-derived NP cells. In NP cells, as well as NP-derived neurons, LIF reduced caspase-mediated apoptosis and reduced both spontaneous and H 2 O 2 -induced reactive oxygen species in culture. In vitro, NP cell proliferation and the yield of differentiated neurons were significantly higher in the presence of LIF. In NP cells, LIF enhanced cMyc phosphorylation, commonly associated with self-renewal/proliferation. Also, in differentiating NP cells LIF activated the phosphoinositide 3-kinase and signal transducer and activator of transcription 3 pathways, associated with cell survival and reduced apoptosis. When differentiated in LIF 1 media, neurite outgrowth and ERK1/2 phosphorylation were potentiated together with increased expression of gp130, a component of the LIF receptor complex. NP cells, pretreated in vitro with LIF, were effective in reducing infarct volume in a model of focal ischemic stroke but LIF did not lead to significantly improved initial NP cell survival over nontreated NP cells. Our results show that LIF signaling significantly promotes human NP cell proliferation, survival, and differentiation in vitro. Activated LIF signaling should be considered in cell culture expansion systems for future human NP cell-based therapeutic transplant studies.

show abstract

Section: Stroke Model Cell Transplantation and Measurement Of Cell mentioning

confidence: 99%

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…As for the function of autophagy in I/R, a growing body of evidence indicates that autophagy, triggered by ischemia may, leads cells to death, especially in the brain [84][85][86][87][88]. However, this depend on cell type and duration of I/R as there are a great number of studies shown autophagy works to keep cells safe from death [89].…”

Section: Autophagy and Ischemia/ Reperfusionmentioning

confidence: 99%

The Role of Autophagy in Stress and Cancer

Bostancıklıoğlu¹

2015

Single Cell Biol

View full text Add to dashboard Cite

Programmed cell death plays an important role in development and disease. There are three main types of programmed cell death: apoptosis, autophagy, and necrosis. Apoptosis works on the two basic pathways called extrinsic and intrinsic; when there is a stress factor in a cell, apoptosis starts. Autophagy is critical for the continuation of normal human physiology such as the cellular homeostasis, energy balance, development and cellular defense. In addition to these, it may play a role in the pathogenesis of cancer, neurodegenerative diseases, aging, muscular diseases, infectious diseases, and immune system diseases.While some autophagy genes showed tumor suppressive effect during the development of cancer, some other genes contributes to the survival of cancer cells during cancer progression. Therefore, the relationship between autophagy and cancer is quite complex. The role of autophagy in cancer varies depending on the stage of the cancer, the metabolic status of cell and the presence of stress. Also, it was reported that the expression of certain molecules associated with autophagy vary in different types of cancer. Autophagy is activated and allows the continuation of the viability of tumor cells in hypoxia. In case of nutrient deficiency, autophagy allows tumor tissue to gain time until nutrient, oxygen and growth factors become eligible again. Therefore, autophagy is seen as a necessary mechanism for tumor continuity. Autophagy increases both in cancer cells and normal cells during the cancer treatment. But, due to cancer cells use autophagy to survive more than normal cells; this case may generate new therapeutic opportunities. The studies needed to conduct to find new ways for using the genes play role in autophagy in cancer treatment.In the present study, we aimed to throw light on the interaction of autophagy mechanism and some stresses such as ischemia and reperfusion and cancer development.

show abstract

“…Compelling evidence suggests neuroprotective effects of neurotensin (8-13) analogs against acute ischemic stroke [12,72,73]. ICV injection of JMV-449, a pseudopeptide analogue of neurotensin (8-13), quickly induced hypothermia and decreased infarct size in mice after MCAO [72].…”

Section: Neurotensin (Nt) Systemmentioning

confidence: 99%

“…ICV injection of JMV-449, a pseudopeptide analogue of neurotensin (8-13), quickly induced hypothermia and decreased infarct size in mice after MCAO [72]. ABS-201 lowered core body temperature by 2-5°C in 15-30 min and maintained body temperature below 35°C for six hours in mice [12]. ABS-201was able to decrease infarct size by 30-40% and to improve long-term neurological function [12].…”

Section: Neurotensin (Nt) Systemmentioning

confidence: 99%

“…During the past decades, studies on hypothermia and ischemic stroke have suggested that the required amplitude of protective hypothermia depends on its time of initiation relative to stroke onset, duration, and depth of hypothermia [1,9,11]. Optimal protection is typically gained when hypothermia is induced as early as possible after stroke onset, with a mild-to-moderate hypothermia of 32 to 35°C that lasts at least one to two hours [1,2,[12][13][14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?

Zhang¹,

Wang²,

Zhao³

et al. 2013

CNSNDDT

View full text Add to dashboard Cite

Ischemic stroke is a common neurological disorder lacking a cure. Recent studies show that therapeutic hypothermia is a promising neuroprotective strategy against ischemic brain injury. Several methods to induce therapeutic hypothermia have been established; however, most of them are not clinically feasible for stroke patients. Therefore, pharmacological cooling is drawing increasing attention as a neuroprotective alternative worthy of further clinical development. We begin this review with a brief introduction to the commonly used methods for inducing hypothermia; we then focus on the hypothermic effects of eight classes of hypothermia-inducing drugs: the cannabinoids, opioid receptor activators, transient receptor potential vanilloid, neurotensins, thyroxine derivatives, dopamine receptor activators, hypothermia-inducing gases, adenosine, and adenine nucleotides. Their neuroprotective effects as well as the complications associated with their use are both considered. This article provides guidance for future clinical trials and animal studies on pharmacological cooling in the setting of acute stroke. KeywordsBrain ischemia; Hypothermic; Neuroprotection; Pharmacological cooling Send correspondence to: Dr. Feng Zhang, Department of Neurology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, PA, 15213, USA, Telephone: 412-383-7604, Fax: 412-648-1239, zhanfx2@upmc.edu NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 1. Hypothermia and strokes IntroductionTherapeutic hypothermia is defined as a 2-6°C reduction of core body temperature [1][2][3] and is a promising neuroprotective approach against brain injury induced by strokes. In hemorrhagic stroke, hypothermia reduces brain edema [4,5] and improves neurologic function [4][5][6][7]. In ischemic stroke, hypothermia is also protective, which has been proven in randomized clinical trials in human cardiac arrest and in animal studies of focal and global ischemia [8,9]. However, the impact of hypothermia on patients with acute ischemic stroke still needs to be explored [10]. During the past decades, studies on hypothermia and ischemic stroke have suggested that the required amplitude of protective hypothermia depends on its time of initiation relative to stroke onset, duration, and depth of hypothermia [1,9,11]. Optimal protection is typically gained when hypothermia is induced as early as possible after stroke onset, with a mild-to-moderate hypothermia of 32 to 35°C that lasts at least one to two hours [1, 2, 12-14]. Protective mechanism of hypothermia in ischemic strokeAlthough hypothermia is effective in protecting against experimental models of ischemic stroke, the precise protective mechanisms are not yet fully understood. It has been suggested that the protective mechanisms are multifold, including reductions in metabolic rate, cerebral blood flow, blood-brain barrier damage, as well as decreases in excitotoxicity, apoptosis, inflammation and free radical production [15]. On average, hypothermia red...

show abstract

A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice

Cited by 88 publications

References 68 publications

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

The Role of Autophagy in Stress and Cancer

Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?

Contact Info

Product

Resources

About