Effects of minocycline on endogenous neural stem cells after experimental stroke

Rueger, Maria Adele; Muesken, S.; Walberer, Maureen; Jantzen, S.; Schnakenburg, K. v.; Backes, Heiko; Graf, Rudolf; Neumaier, Bernd; Hoehn, Mathias; Fink, Gereon R.; Schroeter, Michael

doi:10.1016/j.neuroscience.2012.04.036

Cited by 44 publications

(39 citation statements)

References 48 publications

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“…2,[30][31][32][33] They exhibit improved properties, such as higher relaxivity, better colloidal stability, and easier internalization by cells, compared to commercial contrast agents. 2,[30][31][32][33][34][35] To investigate the role of surface coating on their potential cytotoxicity, we selected three types of SPIONs: uncoated (UnSPIONs), coated with d-mannose (ManSPIONs), and coated with poly-l-lysine (PLLSPIONs). The study was done on neural stem cells (NSCs) as an important model system for regenerative medicine.…”

Section: Introductionmentioning

confidence: 99%

“…The study was done on neural stem cells (NSCs) as an important model system for regenerative medicine. 34 To reveal the possible mechanisms of SPION toxicity, ROS and intracellular GSH levels, mitochondrial membrane potential (MMP), cell MP (CMP), SOD and GPx activity, and DNA damage were examined. Indeed, all of the tested SPIONs showed a substantial influence on NSCs, implying that their use in vivo can be associated with noticeable side effects.…”

Section: Introductionmentioning

confidence: 99%

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Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles

Pongrac¹,

Pavičić²,

Milić³

et al. 2016

IJN

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Biocompatibility, safety, and risk assessments of superparamagnetic iron oxide nanoparticles (SPIONs) are of the highest priority in researching their application in biomedicine. One improvement in the biological properties of SPIONs may be achieved by different functionalization and surface modifications. This study aims to investigate how a different surface functionalization of SPIONs – uncoated, coated with d -mannose, or coated with poly- l -lysine – affects biocompatibility. We sought to investigate murine neural stem cells (NSCs) as important model system for regenerative medicine. To reveal the possible mechanism of toxicity of SPIONs on NSCs, levels of reactive oxygen species, intracellular glutathione, mitochondrial membrane potential, cell-membrane potential, DNA damage, and activities of SOD and GPx were examined. Even in cases where reactive oxygen species levels were significantly lowered in NSCs exposed to SPIONs, we found depleted intracellular glutathione levels, altered activities of SOD and GPx, hyperpolarization of the mitochondrial membrane, dissipated cell-membrane potential, and increased DNA damage, irrespective of the surface coating applied for SPION stabilization. Although surface coating should prevent the toxic effects of SPIONs, our results showed that all of the tested SPION types affected the NSCs similarly, indicating that mitochondrial homeostasis is their major cellular target. Despite the claimed biomedical benefits of SPIONs, the refined determination of their effects on various cellular functions presented in this work highlights the need for further safety evaluations. This investigation helps to fill the knowledge gaps on the criteria that should be considered in evaluating the biocompatibility and safety of novel nanoparticles.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles

Pongrac¹,

Pavičić²,

Milić³

et al. 2016

IJN

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“…After 5 days of FGL treatment, the radiotracer [ 18 F]FLT was systemically injected to label proliferating endogenous NSC in vivo before imaging. On PETimages, the accumulation of [ 18 F]FLT was measured as an in vivo marker for proliferation as described previously Rueger et al 2012). Since we previously observed using [ 18 F]FLT-PET an increased stem cell proliferation induced by FGL under physiologic conditions , we here also employed this translational imaging approach to measure stem cell activation modulated by pharmacological intervention not only ex vivo but also in vivo.…”

Section: Translational Visualization Of Endogenous Nsc After Stroke Imentioning

confidence: 99%

The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke

Klein

Mahlberg

Ohren

et al. 2016

J Neuroimmune Pharmacol

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The neural cell adhesion molecule (NCAM)-derived peptide FG loop (FGL) modulates synaptogenesis, neurogenesis, and stem cell proliferation, enhances cognitive capacities, and conveys neuroprotection after stroke. Here we investigated the effect of subcutaneously injected FGL on cellular compartments affected by degeneration and regeneration after stroke due to middle cerebral artery occlusion (MCAO), namely endogenous neural stem cells (NSC), oligodendrocytes, and microglia. In addition to immunohistochemistry, we used non-invasive positron emission tomography (PET) imaging with the tracer [F]-fluoro-L-thymidine ([F]FLT) to visualize endogenous NSC in vivo. FGL significantly increased endogenous NSC mobilization in the neurogenic niches as evidenced by in vivo and ex vivo methods, and it induced remyelination. Moreover, FGL affected neuroinflammation. Extending previous in vitro results, our data show that the NCAM mimetic peptide FGL mobilizes endogenous NSC after focal ischemia and enhances regeneration by amplifying remyelination and modulating neuroinflammation via affecting microglia. Results suggest FGL as a promising candidate to promote recovery after stroke.

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“…Since [ 11 C]PK11195 is radiolabeled with the isotope 11-C with a half-life of -20 min, sequential PETimaging with [ 18 F]FLT is possible by waiting for -5 half-lives or 100 min between scans. During this time, the animal remains anesthetized within the PET-scanner, avoiding any movement, and enabling an exact co-registration of the imaging data [97] . This co-registered imaging data on […”

Section: Stem Cell-mediated Regeneration After Focal Cerebral Ischemiamentioning

confidence: 99%

“…However, the noninvasive imaging strategies presented here will help to facilitate translation into the clinical setting, and allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs. [97] , with permission. [ …”

Section: Stem Cell-mediated Regeneration After Focal Cerebral Ischemiamentioning

confidence: 99%

In vivoimaging of endogenous neural stem cells in the adult brain

Rueger

Schroeter

2015

WJSC

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The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo , enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intraindividual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3'-deoxy-3'-[18 F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting.

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Effects of minocycline on endogenous neural stem cells after experimental stroke

Cited by 44 publications

References 48 publications

Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles

Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles

The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke

In vivoimaging of endogenous neural stem cells in the adult brain

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