The Efficacy and Safety of Granulocyte Colony-Stimulating Factor for Patients with Stroke

Fan, Zhenzhen; Cai, Hongbin; Ge, Zhao-Ming; Wang, Liqun; Zhang, Xudong; Li, Ling; Zhai, Xiao-Ping

doi:10.1016/j.jstrokecerebrovasdis.2014.11.033

Cited by 18 publications

(12 citation statements)

References 28 publications

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“…These findings represent an important advance in the understanding of the pathophysiology of, and possible treatment for, substance use disorders. Identification of an innate immune effector that is capable of affecting behavioral responses to cocaine has high relevance for potential clinical translation, and recombinant G-CSF has been FDA-approved for many years to treat neutropenia 50 and is now in clinical trials for both stroke 51 and Alzheimer’s disease 52 . The idea of using an immune modulator to treat psychiatric pathology is not novel, and early stage clinical trials of pharmacotherapies aimed at targeting the immune system have shown promise in treating major depressive disorder 53 .…”

Section: Discussionmentioning

confidence: 99%

Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine

et al. 2018

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Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF injections potentiate cocaine place preference and enhance motivation to self-administer cocaine, while not affecting responses to natural rewards. Infusion of G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate cocaine’s behavioral effects, providing a direct link between central G-CSF action in NAc and cocaine reward. These results demonstrate that manipulating G-CSF is sufficient to alter the motivation for cocaine, but not natural rewards, providing a pharmacotherapeutic avenue to manipulate addictive behaviors without abuse potential.

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Section: Discussionmentioning

confidence: 99%

Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine

et al. 2018

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“…Moreover, G-CSF may foster functional recovery, as measured by the National Institutes of Health Stroke Scale and modified Rankin Scale scores. 48 …”

Section: Cellular Replacement Therapiesmentioning

confidence: 99%

Neurorestoration after stroke

Azad¹,

Veeravagu²,

Steinberg³

2016

FOC

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Recent advancements in stem cell biology and neuromodulation have ushered in a battery of new neurorestorative therapies for ischemic stroke. While the understanding of stroke pathophysiology has matured, the ability to restore patients' quality of life remains inadequate. New therapeutic approaches, including cell transplantation and neurostimulation, focus on reestablishing the circuits disrupted by ischemia through multidimensional mechanisms to improve neuroplasticity and remodeling. The authors provide a broad overview of stroke pathophysiology and existing therapies to highlight the scientific and clinical implications of neurorestorative therapies for stroke.

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“…A recent meta-analysis of Chinese origin describing results in favour of G-CSF includes 4 Chinese publications that did not appear in our systematic searches22. Attempts to obtain further detail on these publications from the authors were unsuccessful.…”

Section: Resultsmentioning

confidence: 99%

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis

England

Sprigg

Алашеев

et al. 2016

Sci Rep

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Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of-trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-totreatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5-15), randomised 11 days (interquartile range IQR 4-238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p = 0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p = 0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p = 0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis.

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The Efficacy and Safety of Granulocyte Colony-Stimulating Factor for Patients with Stroke

Cited by 18 publications

References 28 publications

Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine

Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine

Neurorestoration after stroke

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis

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