Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Shin, Tae Kyeong; Kang, Mi Sun; Lee, Ho Youn; Seo, Moo Sang; Kim, Si Geun; Kim, Chi Dae; Lee, Won Suk

doi:10.4196/kjpp.2009.13.3.257

Cited by 56 publications

(40 citation statements)

References 55 publications

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“…Recent studies showed that 14 days of treatment with fluoxetine and sertraline, starting 1hr after the ischaemic insult significantly reduced photothrombosis-induced infarct size in mice [35], and significantly increased the expression of haem oxygenase-1 (HO-1) and hypoxia-inducible factor-1α in the ischaemic region [35]. Compatible with these reports, we found the long-lasting vasodilatation of brain arterioles induced by clinically relevant concentrations of fluoxetine to associate with increased blood flow through the ischaemic and per-ischaemic regions.…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

Ofek

Schoknecht

Melamed-Book

et al. 2012

J Cellular Molecular Medi

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Ischaemic stroke patients treated with Selective Serotonin Reuptake Inhibitors (SSRI) show improved motor, cognitive and executive functions, but the underlying mechanism(s) are incompletely understood. Here, we report that cerebral arterioles in the rat brain superfused with therapeutically effective doses of the SSRI fluoxetine showed consistent, dose-dependent vasodilatation (by 1.2 to 1.6-fold), suppressible by muscarinic and nitric oxide synthase (NOS) antagonists [atropine, NG-nitro-l-arginine methyl ester (l-NAME)] but resistant to nicotinic and serotoninergic antagonists (mecamylamine, methylsergide). Fluoxetine administered 10–30 min. following experimental vascular photo-thrombosis increased arterial diameter (1.3–1.6), inducing partial, but lasting reperfusion of the ischaemic brain. In brain endothelial b.End.3 cells, fluoxetine induced rapid muscarinic receptor-dependent increases in intracellular [Ca2+] and promoted albumin- and eNOS-dependent nitric oxide (NO) production and HSP90 interaction. In vitro, fluoxetine suppressed recombinant human acetylcholinesterase (rhAChE) activity only in the presence of albumin. That fluoxetine induces vasodilatation of cerebral arterioles suggests co-promotion of endothelial muscarinic and nitric oxide signalling, facilitated by albumin-dependent inhibition of serum AChE.

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Section: Discussionmentioning

confidence: 99%

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

Ofek

Schoknecht

Melamed-Book

et al. 2012

J Cellular Molecular Medi

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“…Permanent focal ischemia was induced by cortical photothrombotic vascular occlusion according to the method of Schroeter et al [30] with a slight modification as described previously [31]. The mice were anesthetized with chloral hydrate (450 mg/kg, i.p.…”

Section: Photothrombotic Cortical Ischemiamentioning

confidence: 99%

“…The infarct size, including the infarct area and volume, was measured as described previously [31]. The mice were anesthetized with urethane (1 g/kg, i.p.)…”

Section: Easurement Of Infarct Sizementioning

confidence: 99%

Matrix Metalloproteinase Inhibitors Attenuate Neuroinflammation Following Focal Cerebral Ischemia in Mice

Park

Shin

Lee

et al. 2011

Korean J Physiol Pharmacol

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The aim of this study was to investigate whether matrix metalloproteinase (MMP) inhibitors attenuate neuroinflammation in an ischemic brain following photothrombotic cortical ischemia in mice. Male C57BL/6 mice were anesthetized, and Rose Bengal was systemically administered. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold white light. MMP inhibitors, such as doxycycline, minocycline, and batimastat, significantly reduced the cerebral infarct size, and the expressions of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α ), and indoleamine 2,3-dioxygenase (IDO). However, they had no effect on the expressions of heme oxygenase-1 and neuroglobin in the ischemic cortex. These results suggest that MMP inhibitors attenuate ischemic brain injury by decreasing the expression levels of MCP-1, TNF-α , and IDO, thereby providing a therapeutic benefit against cerebral ischemia.

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“…The brain slices were incubated in phosphate-buffered saline (PBS; pH 7.4) containing 2% 2, 3, 5-triphenyl tetrazolium chloride (TTC, Sigma, MO. U.S.A.) at 37 o C for 30 min and were fixed by immersion in 10% neutral buffered formalin solution [13]. The caudal face of each section was scanned using a flatbed color scanner and the images were stored.…”

Section: Easurement Of Infarct Volumementioning

confidence: 99%

Neuroprotection by Valproic Acid in Mouse Models of Permanent and Transient Focal Cerebral Ischemia

Qian

Lee

Hwang

et al. 2010

Korean J Physiol Pharmacol

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Valproic acid (VPA) is a well-known anti-epileptic and mood stabilizing drug. A growing number of reports demonstrate that VPA is neuroprotective against various insults. Despite intensive efforts to develop new therapeutics for stroke over the past two decades, all treatments have thus far failed to show clinical effect because of treatment-limiting side effects of the drugs. Therefore, a safety-validated drug like VPA would be an attractive candidate if it has neuroprotective effects against ischemic insults. The present study was undertaken to examine whether pre-and post-insult treatments with VPA protect against brain infarct and neurological deficits in mouse transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) models. In the tMCAO (2 hr MCAO and 22 hr reperfusion) model, intraperitoneal injection of VPA (300 mg/kg, i.p.) 30 min prior to MCAO significantly reduced the infarct size and the neurological deficit. VPA treatment immediately after reperfusion significantly reduced the infarct size. The administration of VPA at 4 hr after reperfusion failed to reduce the infarct size and the neurological deficit. In the pMCAO model, treatment with VPA (300 mg/kg, i.p.) 30 min prior to MCAO significantly attenuated the infarct size, but did not affect the neurological deficit. W estern blot analysis of acetylated H3 and H4 protein levels in extracts from the ischemic cortical area showed that treatment with VPA increased the expression of acetylated H3 and H4 at 2 hrs after MCAO. These results demonstrated that treatment with VPA prior to ischemia attenuated ischemic brain damage in both mice tMCAO and pMCAO models and treatment with VPA immediately after reperfusion reduced the infarct area in the tMCAO model. VPA could therefore be evaluated for clinical use in stroke patients.

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Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Cited by 56 publications

References 55 publications

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

Matrix Metalloproteinase Inhibitors Attenuate Neuroinflammation Following Focal Cerebral Ischemia in Mice

Neuroprotection by Valproic Acid in Mouse Models of Permanent and Transient Focal Cerebral Ischemia

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