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

Abstract

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.

Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds

“…The MPO-mediated nitrosative stress could be a potential player in mediating hemorrhagic transformation in ischemic stroke with the delayed t-PA treatment. Notably, treatment of taurine, a HOCl scavenger, reduced the rates of hemorrhage transformation in experimental ischemic stroke animal model with delayed t-PA treatment (Guan et al, 2011). Hence, the production of HOCl might be a crucial cytotoxic factor in the MPO-mediated oxidative injury and inflammation.…”

Comparison between single and combined post-treatment with S-Methyl-N,N-diethylthiolcarbamate sulfoxide and taurine following transient focal cerebral ischemia in rat brain

“…Taurine as a neurotransmitter, neuromodulator, membrane stabilizer, and major intracellular free amino acid has been employed in experimental therapies against neuronal damage, hypoxia, and epilepsy in several studies (Birdsall, 1998;Louzada, 2004;Sun and Xu, 2008;Sun et al, 2011). We and other investigators have previously shown that post-stroke treatment with taurine can reduce rat neurological deficits, brain infarct volume, and also caspase-3 activities in the ischemic penumbra following middle cerebral artery occlusion (MCAO) (Guan et al, 2011;Sun et al, 2011;Gharibani et al, 2013). Moreover, taurine inhibited the endoplasmic reticulum (ER) stress-induced apoptosis by activating transcription factor 6 (ATF6) and the inositol requiring enzyme 1 (IRE1) pathway, but not the protein kinase R-like endoplasmic reticulum kinase (PERK) pathway (Pan et al, 2010;Gharibani et al, 2013).…”

Lactulose Improves Neurological Outcomes by Repressing Harmful Bacteria and Regulating Inflammatory Reactions in Mice After Stroke

“…Taurine has cytoprotective, antioxidative stress, anti-inflammatory, and barrier integrity-maintaining effects ( Schaffer and Kim, 2018 ; Jakaria et al., 2019 ). In animal experiments and clinical trials, taurine has been used to treat neurological ( Hou et al., 2018 ; Ohsawa et al., 2019 ), cardiovascular ( Katakawa et al., 2016 ), and metabolic diseases ( Obrosova et al., 2001 ), especially stroke ( Guan et al., 2011 ; Sun et al., 2012 ; Jin et al., 2018 ). Our study found that taurine was decreased after stroke and increased by lactulose, which perhaps could explain the good neurological performance of the PTS_LAC group.…”