Neuroprotective Mechanism of Taurine due to Up-regulating Calpastatin and Down-regulating Calpain and Caspase-3 during Focal Cerebral Ischemia

Sun, Ming; Xu, Chao

doi:10.1007/s10571-007-9183-8

Cited by 59 publications

(32 citation statements)

References 72 publications

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“…The mechanism by which taurine acts has been discussed in the literature for many years without a clear answer. Our data support the assumption that taurine outbalances possible negative effects of PuriProtect caused by its molecular composition [22,23,24]. In general, the ERG data should be considered to be more valuable than the data from the cell culture experiments because it focuses on the functional analysis and is more reliable than histological, ultrastructural or biochemical analysis [25].…”

Section: Discussionsupporting

confidence: 80%

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Comparing the Effects of Two Different Irrigation Solutions on an Isolated Perfused Vertebrate Retina

Januschowski

Maddani²,

Mueller³

et al. 2012

Ophthalmic Res

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Purpose: To compare the effect of a taurine-containing intraocular irrigation solution (PuriProtect™) to a standard irrigation solution (BSS™) we evaluated the retinal function using an electroretinogram (ERG) and analyzed the survival of retinal ganglion cells on isolated whole mount retinas. Materials and Methods: During ERG recordings, each irrigation solution was superfused for 45 min with the relevant irrigation solution. To investigate the effects on photoreceptor function, 1 mM asparate was added to obtain a-waves. The recovery of the a- and b-wave was monitored after superfusing the retinas with standard medium again. To evaluate the percentage of dead ganglion cells, retinas were stored for 24 h at 4°C in darkness and after staining the retinas with ethidium homodimer-1 the retinas were analyzed using fluorescence microscopy. Results: The application of standard medium supplemented with 2 mM taurine resulted in a significant increase of the b-wave amplitude compared to standard medium alone. The a-wave amplitudes showed no significant changes under taurine supplementation. Compared to standard medium BSS showed no significant decrease in b-wave amplitudes, but a significant decrease in a-wave amplitudes. In contrast to BSS there were no significant changes in the a- or b-wave amplitudes detectable after the application of PuriProtect. At the end of the washout period no significant changes in a- or b-wave amplitudes were recorded for any tested irrigation solution. Retinas stored for 24 h in PuriProtect or in standard medium with taurine had a statistically significant smaller amount of dead cells than retinas stored in standard medium without taurine supplementation. Conclusions: BSS does not seem to be an ideal irrigation solution, because it compromises the a-wave in the ERG. In contrast to BSS, PuriProtect showed no significant impact on the ERG and showed a better long-term effect on ganglion cell survival. Taurine supplementation, therefore, seems to be neuroprotective and its supplementation to an intraocular irrigation solution favorable for the retina.

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Section: Discussionsupporting

confidence: 80%

“…This is supported by data from Lüke et al [14 ]and from Sun and Xu [22], who could not show negative effects of taurine on the ERG and on cell cultures. Taking a look at the molecular composition of PuriProtect, which is very similar to BSS, this seems surprising.…”

Section: Discussionsupporting

confidence: 73%

Comparing the Effects of Two Different Irrigation Solutions on an Isolated Perfused Vertebrate Retina

Januschowski

Maddani²,

Mueller³

et al. 2012

Ophthalmic Res

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“…Taurine may mediate its protective action on neurons either by directly blocking the m-calpain and caspase-3-mediated apoptotic cell death pathways in ischemia or by increasing mitochondrial buffering of calcium in glutamate-induced neuronal excitotoxicity [9][10][11] . However, little attention has been directed to hypoxia-induced retinal cell damage and potential mechanisms of the protective role of taurine.…”

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confidence: 99%

Taurine Buffers Glutamate Homeostasis in Retinal Cells in vitro under Hypoxic Conditions

Chen

Zhang

et al. 2010

Ophthalmic Res

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Aims: We investigated whether taurine indirectly protects neurons under hypoxia by affecting retinal Müller cells, which are known to play important roles in the regulation of retinal glutamate content. Methods: Retinal cells isolated from rats were exposed to hypoxia for 24 h. We evaluated the retinal neuron survival, glutamate content in cultures with and without taurine under hypoxic conditions. The glutamate clearance function correlated with the expression of glutamine synthetase (GS) mRNA and L-glutamate/L-aspartate transporter (GLAST) mRNA. Immunohistochemical staining of glial fibrillary acidic protein (GFAP), vimentin and S-100 protein was performed to examine cytoskeletal changes in retinal Müller cells. Results: Retinal neurons treated with taurine exhibited significantly higher survival rates than those without taurine under hypoxia. Taurine inhibited the upregulation of GFAP and vimentin, and inhibited the downregulation of GLAST, GS and the nuclear-cytoplasmic ratio of S-100 under hypoxia. In addition, taurine inhibited the upregulation of the glutamate content in neurons and retinal Müller cells upon hypoxic exposure. Conclusion: These data suggest that hypoxic damage to cultured retinal cells is decreased by taurine. The neuroprotection by taurine may relate to buffering glutamate homeostasis via modulation of the glutamate clearance by retinal Müller cells.

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“…Our previous studies have already proven that exogenous administration of taurine can significantly decrease the infarct volume and improve the neurological outcome in the mechanical stroke model of rat [14]. In the present study, we test the hypothesis that intravenous administration of taurine in combination with intra-arterial administration of urokinase enhances efficacy of thrombolysis and neuroprotection, in addition, extends the therapeutic window of stroke in a rat model of embolic stroke.…”

Section: Introductionmentioning

confidence: 75%

A Combined Treatment with Taurine and Intra-arterial Thrombolysis in an Embolic Model of Stroke in Rats: Increased Neuroprotective Efficacy and Extended Therapeutic Time Window

Guan

Zhao

2010

Transl. Stroke Res.

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Combination treatment may target different pathophysiological events following cerebral ischemia thus enhancing the efficacy of treatment in thromboembolic stroke. Taurine confers a neuroprotective effect in the mechanical stroke model. This effect has not been assessed in an embolic stroke model. Here, we sought to evaluate the neuroprotective effect of taurine alone and in combination with thrombolytic therapy to investigate whether combined administration would extend the therapeutic time window without increasing the hemorrhagic transformation in a rat embolic stroke model. Rats were subjected to right embolic middle cerebral artery occlusion and then randomly assigned to the following groups: saline treatment alone at 4 h, urokinase, taurine treatment alone at 4, 6, or 8 h, and the combination of taurine and urokinase at 4, 6, or 8 h after the insult. Brain infarct volume, neurobehavioral outcome, regional cerebral blood flow, intracranial hemorrhage incidence were observed and evaluated. Posttreatment with taurine at 4 or 6 h, urokinase at 4 h or in combination at 4, 6, or 8 h significantly reduced infarct volume and improved neurobehavioral outcome. The combination treatment had better neurobehavioral outcome and smaller infarction volume than urokinase or taurine treatment alone. The clinical outcome correlated well with infarct volume. Together, the present study suggests that administration of taurine after stroke is neuroprotective, seemingly because it reduces the reperfusion damage of urokinase, leading to widen the therapeutic window for the thrombolytic effect of urokinase to 8 h. Thrombolysis can also enhance the neuroprotective effect of taurine. The reduction of inflammatory response, neuron death and inhibition of blood brain barrier (BBB) disruption may underlie the beneficial effects of combination of taurine and urokinase in the treatment of embolic stroke.

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Neuroprotective Mechanism of Taurine due to Up-regulating Calpastatin and Down-regulating Calpain and Caspase-3 during Focal Cerebral Ischemia

Abstract: Our data demonstrate the dose-dependent neuroprotection of taurine against transient focal cerebral ischemia, and suggest that one of protective mechanisms of taurine against ischemia may be blocking the m-calpain and caspase-3-mediated apoptotic cell death pathways.

Cited by 59 publications

References 72 publications

Comparing the Effects of Two Different Irrigation Solutions on an Isolated Perfused Vertebrate Retina

Comparing the Effects of Two Different Irrigation Solutions on an Isolated Perfused Vertebrate Retina

Taurine Buffers Glutamate Homeostasis in Retinal Cells in vitro under Hypoxic Conditions

A Combined Treatment with Taurine and Intra-arterial Thrombolysis in an Embolic Model of Stroke in Rats: Increased Neuroprotective Efficacy and Extended Therapeutic Time Window

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