Neuroprotective effects of a novel water-soluble poly(ADP-ribose) polymerase-1 inhibitor, MP-124, in in vitro and in vivo models of cerebral ischemia

Hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) are the main water-soluble compounds in Carthamus tinctorius L. However, studies on the effect of AHSYB on cerebral ischemia/reperfusion (I/R) injury and the therapeutic effect of HSYA by regulating silent information regulator 1 (SIRT1) pathway remain obscure. In this study, we investigated whether the neuroprotective effects of HSYA and AHSYB on oxygen-glucose deprivation/reoxygenation in primary-cultured hippocampal neuronal cells and the middle cerebral artery occlusion and reperfusion model in rats are associated with the regulation of the SIRT1 pathway. In vitro, HSYA and AHSYB increased cell viability, depressed oxidation properties, and reduced neuronal cell apoptosis. In vivo results showed that HSYA and AHSYB effectively reduced infarct volume, improved neurological function, suppressed apoptosis, and decreased the oxidative stress reaction. Besides, RT-PCR and Western blot analysis showed that HSYA and AHSYB increased the mRNA and protein expressions of the main factors in the SIRT1 pathway, including SIRT1, forkhead box O (FOXO) 1, and peroxisome proliferator–activated receptor coactivator 1α (PGC1α), decreased the expression of Bax, and increased the expression of Bcl-2. The results from immunohistochemistry also showed that the expressions of SIRT1, FOXO1, and PGC1α were increased after treatment with HSYA and AHSYB. Furthermore, the neuroprotective effects of HSYA and AHSYB were abolished by EX527 (SIRT1–specific inhibitor). These results indicated that HSYA and AHSYB should be developed into potential drugs for treating cerebral I/R injury via the SIRT1 pathway. Although HSYA and AHSYB have different chemical structures, both of them exert similar neuroprotective properties against I/R injury in vitro and in vivo, which means that AHSYB is also a non-negligible component in safflower.

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Neuroprotective Effects of Insulin-Like Growth Factor-Binding Protein Ligand Inhibitors in Vitro and in Vivo

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/01.wcb.0000087091.01171.ae ◽

2003 ◽

Vol 23 (10) ◽

pp. 1160-1167 ◽

Cited By ~ 39

Author(s):

Kenneth B Mackay ◽

Sarah A Loddick ◽

Gregory S Naeve ◽

Alicia M Vana ◽

Gail M Verge ◽

...

Keyword(s):

Cerebral Ischemia ◽

Infarct Size ◽

Infarct Volume ◽

Artery Occlusion ◽

Dependent Manner ◽

Neuroprotective Effects ◽

In Vivo Models ◽

Igf I

The role of brain insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in neuroprotection was further investigated using in vitro and in vivo models of cerebral ischemia by assessing the effects of IGF-I, IGF-II, and high affinity IGFBP ligand inhibitors (the peptide [Leu24, 59, 60, Ala31]hIGF-I (IGFBP-LI) and the small molecule NBI-31772 (1-(3,4-dihydroxybenzoyl)-3-hydroxycarbonyl-6, 7-dihydroxyisoquinoline), which pharmacologically displace and elevate endogenous, bioactive IGFs from IGFBPs. Treatment with IGF-I, IGF-II, or IGFBP-LI (2 μg/mL) significantly ( P < 0.05) reduced CA1 damage in organotypic hippocampal cultures resulting from 35 minutes of oxygen and glucose deprivation by 71%, 60%, and 40%, respectively. In the subtemporal middle cerebral artery occlusion (MCAO) model of focal ischemia, intracerebroventricular (icv) administration of IGF-I and IGF-II at the time of artery occlusion reduced ischemic brain damage in a dose-dependent manner, with maximum reductions in total infarct size of 37% ( P < 0.01) and 38% ( P < 0.01), respectively. In this model of MCAO, icv administration of NBI-31772 at the time of ischemia onset also dose-dependently reduced infarct size, and the highest dose (100 μg) significantly reduced both total (by 40%, P < 0.01) and cortical (by 43%, P < 0.05) infarct volume. In the intraluminal suture MCAO model, administration of NBI-31772 (50 μg icv) at the time of artery occlusion reduced both cortical infarct volume (by 40%, P < 0.01) and brain swelling (by 24%, P < 0.05), and it was still effective when treatment was delayed up to 3 hours after the induction of ischemia. These results further define the neuroprotective properties of IGFs and IGFBP ligand inhibitors in experimental models of cerebral ischemia.

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In Vitro and In Vivo Models of Cerebral Ischemia Show Discrepancy in Therapeutic Effects of M2 Macrophages

PLoS ONE ◽

10.1371/journal.pone.0067063 ◽

2013 ◽

Vol 8 (6) ◽

pp. e67063 ◽

Cited By ~ 31

Author(s):

Virginie Desestret ◽

Adrien Riou ◽

Fabien Chauveau ◽

Tae-Hee Cho ◽

Emilie Devillard ◽

...

Keyword(s):

Cerebral Ischemia ◽

Therapeutic Effects ◽

M2 Macrophages ◽

In Vivo Models

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ROS-Dependent Neuroprotective Effects of NaHS in Ischemia Brain Injury Involves the PARP/AIF Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000430317 ◽

2015 ◽

Vol 36 (4) ◽

pp. 1539-1551 ◽

Cited By ~ 35

Author(s):

Qian Yu ◽

Zhihong Lu ◽

Lei Tao ◽

Lu Yang ◽

Yu Guo ◽

...

Keyword(s):

Brain Injury ◽

Focal Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Dependent Manner ◽

Neuroprotective Effects ◽

Ht22 Cells ◽

In Vivo Models ◽

The Brain

Background/Aims: Stroke is among the top causes of death worldwide. Neuroprotective agents are thus considered as potentially powerful treatment of stroke. Methods: Using both HT22 cells and male Sprague-Dawley rats as in vitro and in vivo models, we investigated the effect of NaHS, an exogenous donor of H2S, on the focal cerebral ischemia-reperfusion (I/R) induced brain injury. Results: Administration of NaHS significantly decreased the brain infarcted area as compared to the I/R group in a dose-dependent manner. Mechanistic studies demonstrated that NaHS-treated rats displayed significant reduction of malondialdehyde content, and strikingly increased activity of superoxide dismutases and glutathione peroxidase in the brain tissues compared with I/R group. The enhanced antioxidant capacity as well as restored mitochondrial function are NaHS-treatment correlated with decreased cellular reactive oxygen species level and compromised apoptosis in vitro or in vivo in the presence of NaHS compared with control. Further analysis revealed that the inhibition of PARP-1 cleavage and AIF translocation are involved in the neuroprotective effects of NaHS. Conclusion: Collectively, our results suggest that NaHS has potent protective effects against the brain injury induced by I/R. NaHS is possibly effective through inhibition of oxidative stress and apoptosis.

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Brazilian Green Propolis Protects against Retinal Damage In Vitro and In Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nek005 ◽

2006 ◽

Vol 3 (1) ◽

pp. 71-77 ◽

Cited By ~ 41

Author(s):

Yuta Inokuchi ◽

Masamitsu Shimazawa ◽

Yoshimi Nakajima ◽

Shinsuke Suemori ◽

Satoshi Mishima ◽

...

Keyword(s):

Oxidative Stress ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Water Soluble ◽

Retinal Damage ◽

Retinal Ganglion ◽

Neuroprotective Effects ◽

Brazilian Green Propolis

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retinain vitroand/orin vivo.In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In micein vivo, propolis (100 mg kg−1; intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitrealin vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage bothin vitroandin vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

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A Novel and Potent Poly(ADP-Ribose) Polymerase-1 Inhibitor, FR247304 (5-Chloro-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazolinone), Attenuates Neuronal Damage in in Vitro and in Vivo Models of Cerebral Ischemia

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.104.066944 ◽

2004 ◽

Vol 310 (2) ◽

pp. 425-436 ◽

Cited By ~ 63

Author(s):

Akinori Iwashita ◽

Nobuteru Tojo ◽

Shigeru Matsuura ◽

Syunji Yamazaki ◽

Kazunori Kamijo ◽

...

Keyword(s):

Cerebral Ischemia ◽

Neuronal Damage ◽

In Vivo Models

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Conjugates of cis-4-Hydroxy-L-proline and Poly(PEG-Lys), a Water Soluble Poly(ether urethane): Synthesis and Evaluation of Antifibrotic Effects in vitro and in vivo

Bioconjugate Chemistry ◽

10.1021/bc00030a018 ◽

1994 ◽

Vol 5 (6) ◽

pp. 621-630 ◽

Cited By ~ 9

Author(s):

George J. Poiani ◽

David J. Riley ◽

James D. Fox ◽

John E. Kemnitzer ◽

K. Fiorella Gean ◽

...

Keyword(s):

Water Soluble ◽

Soluble Poly

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Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2015.02.030 ◽

2015 ◽

Vol 84 ◽

pp. 331-343 ◽

Cited By ~ 84

Author(s):

Zaijun Zhang ◽

Guohui Li ◽

Samuel S.W. Szeto ◽

Cheong Meng Chong ◽

Quan Quan ◽

...

Keyword(s):

Parkinson Disease ◽

Protocatechuic Acid ◽

Neuroprotective Effects ◽

In Vivo Models

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Hypothermia and Isoflurane Similarly Inhibit Glutamate Release Evoked by Chemical Anoxia in Rat Cortical Brain Slices

Anesthesiology ◽

10.1097/00000542-199609000-00020 ◽

1996 ◽

Vol 85 (3) ◽

pp. 600-607. ◽

Cited By ~ 35

Author(s):

Helge Eilers ◽

Philip E. Bickler

Keyword(s):

Minimum Alveolar Concentration ◽

Glutamate Release ◽

Brain Slices ◽

Neuronal Cell ◽

Release Rates ◽

Neuroprotective Effects ◽

In Vivo Models ◽

Chemical Anoxia

Background Accumulation of the excitatory neurotransmitter glutamate in ischemic brain tissue contributes to neuronal cell death. Volatile anesthetics at clinically relevant concentrations are neuroprotective in in vivo models of brain ischemia and reduce glutamate release in vivo and in vitro, but they appear to have weaker neuroprotective effects than hypothermia. The purpose of this study was to determine whether isoflurane reduces glutamate release in hypoxic brain slices, how large this effect is compared to that of hypothermia, and if it is diminished by hyperthermia. Methods Glutamate released from rat cortical brain slices during chemical anoxia (100 microM NaCN) was measured continuously with a fluorescence assay. The release rate was compared at three temperatures (28 degrees C, 37 degrees C, and 39 degrees C) with and without isoflurane at concentrations equipotent to 1 minimum alveolar concentration. At the same three temperatures, glutamate release rates before and after exposure to isoflurane were compared. Results Isoflurane reduced glutamate release from brain slices during chemical anoxia at 37 degrees C (19.6%, P < 0.01) and at 39 degrees C (25.4%, P < 0.01), but not at 28 degrees C. The reduction in glutamate release with hypothermia was similar to that with isoflurane. Hyperthermia (39 degrees C) caused greater glutamate release under basal and anoxic conditions than normo- and hypothermia. Isoflurane caused a slight increase in basal glutamate release rates, although this effect was smaller than the increase caused by hyperthermia. Conclusions In a brain slice model of cerebral anoxia, 1 minimum alveolar concentration isoflurane decreases glutamate release to a similar extent that hypothermia (28 degrees C) does. The increased glutamate release with hyperthermia (39 degrees C) is not prevented by isoflurane.

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