Ziprasidone attenuates brain injury after focal cerebral ischemia induced by middle cerebral artery occlusion in rats

Kam, Kyung-Yoon; Jalin, Angela M.A.Anthony; Choi, Yong Won; Kaengkan, Phatcharida; Park, Sung Woo; Kim, Young Hoon; Kang, Sung Goo

doi:10.1016/j.pnpbp.2012.05.010

Cited by 10 publications

(9 citation statements)

References 52 publications

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“…In the previous and present study, treatment with ziprasidone facilitated neurological recovery after MCAO as measured by mNSS, which scores severity in motor, sensory, reflex, and balance functions (Kam et al, 2012). The recovery may be attributed to reduction by ziprasidone treatment in the size of the infarct area induced by MCAO, which includes the cortex and the striatum that are mainly related to sensory perception and to motor control.…”

Section: Discussionsupporting

confidence: 65%

“…Recent studies have reported that atypical antipsychotics have neuroprotective effects against brain injury. Acute treatment with ziprasidone significantly improved neurological functions in ischemic brain injury and this provides a new insight for its clinical applications (Kam et al, 2012;Takahashi et al, 2008). Several mechanisms have been examined to explain the neuroprotective actions of atypical antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

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Administration of Mesenchymal Stem Cells and Ziprasidone Enhanced Amelioration of Ischemic Brain Damage in Rats

Kaengkan

Baek

Kim

et al. 2013

Molecules and Cells

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Ziprasidone is a benzisothiazolyl piperazine derivative that was developed from the chemically related antipsychotic drug tiospirone, and it improves neurological functions of the ischemic brain and is effective in treatment of schizophrenia. Mesenchymal stem cells (MSCs) are considered as a leading candidate for neurological regenerative therapy because of their neural differentiation properties in damaged brain. We investigated whether the transplantation of neural progenitor cells (NPCs) derived from adipose mesenchymal stem cells combined with ziprasidone enhances neuroprotective effects in an animal model of focal cerebral ischemia. In combination therapy groups, significant reduction of infarct volume and improvement of neurological functions were observed at 3 days after middle cerebral artery occlusion (MCAO) compared with monotherapy. Co-administration of ziprasidone and NPCs enhanced the anti-apoptotic effect and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with the NPCs alone group at 7 days after MCAO. Ziprasidone or the combination of ziprasidone and NPCs induced the expression of endogenous neurotrophic factor gene brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF). The immunohistochemical investigation revealed that the ziprasidone and NPCs attenuated the increased intensity of microglial marker (Iba-1) in the infarcted cortical area. Moreover, the number of transplanted NPCs on day 7 with combination therapy was significantly higher than with NPCs alone. These effects might be responsible for improved functional behavior and increased survival of NPCs. Our finding indicates that combination therapy of ziprasidone and NPCs enhances neuroprotection against ischemic brain injury.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Administration of Mesenchymal Stem Cells and Ziprasidone Enhanced Amelioration of Ischemic Brain Damage in Rats

Kaengkan

Baek

Kim

et al. 2013

Molecules and Cells

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“…The antiserotonergic and antidopaminergic effects of antipsychotics are believed to reduce the release of neurotransmitters, and this will decrease the excitotoxic effect of glutamate which may, in turn, protect the neurons [10]. However, animal studies are ambiguous; dopamine receptor antagonists may impair recovery after brain damage in rats [11]–[13], although recent studies have found that focal ischemic brain damage was reduced in mice if various antipsychotics were given while ischemia was being induced [2]–[5].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, animal studies of acute stroke have indicated that antipsychotic medication may have neuroprotective effects that are related to their antiserotonergic and antidopaminergic mechanisms of action leading to reduced effects of glutamate [2]–[5]. A reduced effect of glutamate may theoretically decrease excitotoxicity and increase neuronal survival [6]–[10], but current results are ambiguous [11]–[13].…”

Section: Introductionmentioning

confidence: 99%

Post-Stroke Mortality, Stroke Severity, and Preadmission Antipsychotic Medicine Use – A Population-Based Cohort Study

et al. 2014

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Background and PurposeIt has been suggested that antipsychotic medication may be neuroprotective and may reduce post-stroke mortality, but studies are few and ambiguous. We aimed to investigate the post-stroke effects of preadmission antipsychotic use.MethodsWe conducted a nationwide, population-based cohort study of 81,143 persons admitted with stroke in Denmark from 2003–2010. Using Danish health care databases, we extracted data on preadmission use of antipsychotics and confounding factors. We examined the association between current, former, and never use of antipsychotics and stroke severity, length of hospital stay, and 30-day post-stroke mortality using logistic regression analysis, survival analysis, and propensity score matching.ResultsCurrent users of antipsychotics had a higher risk of severe or very severe stroke on The Scandinavian Stroke Scale than never users of antipsychotics (adjusted odds ratios, 1.43; 95% CI, 1.29–1.58). Current users were less likely to be discharged from hospital within 30 days of admission than never users (probability of non-discharge, 27.0% vs. 21.9%). Antipsychotics was associated with an increased 30-day post-stroke mortality among current users (adjusted mortality rate ratios, 1.42; 95% CI, 1.29–1.55), but not among former users (adjusted mortality rate ratios, 1.05; 95% CI, 0.98–1.14).ConclusionsPreadmission use of antipsychotics was associated with a higher risk of severe stroke, a longer duration of hospital stay, and a higher post-stroke mortality, even after adjustment for known confounders. Antipsychotics play an important role in the treatment of many psychiatric conditions, but our findings do not support the hypothesis that they reduce stroke severity or post-stroke mortality.

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“…The result is a significant reduction in blood flow and energy failure critical for neural function and survival. Clinical studies report that memory damage and cognitive impairment are observed in cerebral ischemia (Nunn and Hodges, 1994;Kruyt et al, 2008;Kam et al, 2012). The cholinergic neurons play an important role in cognitive function and sensitive to cerebral ischemia (Block, 1999;Zhang et al, 2010 Keyser et al, 1999;Kaengkan et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Effects of Rice Bran Extracts Fermented with Lactobacillus plantarum on Neuroprotection and Cognitive Improvement in a Rat Model of Ischemic Brain Injury

Hong

Kim

Baek

et al. 2015

BSL

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This work aimed to study whether rice bran extract fermented with Lactobacillus plantarum (LW) promotes functional recovery and reduces cognitive impairment after ischemic brain injury. Ischemic brain injury was induced by middle cerebral artery occlusion (MCAO) in rats. Four groups were studied, namely the (1) sham, (2) vehicle, (3) donepezil, and (4) LW groups. Animals were injected with LW once a day for 7 days after middle cerebral artery occlusion. LW group showed significantly improved neurological function as compared to the vehicle group, as well as enhanced learning and memory in the Morris water maze. The LW group showed the greatest functional recovery. Moreover, the LW group showed an enhanced more survival cells anti-apoptotic effect in the cortex and neural cell densities in the hippocampal DG and CA1. In addition, this group showed enhanced expression of neurotrophic factors, antioxidant genes, and the acetylcholine receptor gene, as well as synaptophysin (SYP), Fox-3 (NeuN), doublecortin (DCX), and choline acetyltransferase (ChAT) proteins. Our findings indicate that LW treatment showed the largest effects in functional recovery and cognitive improvement after ischemic brain injury through stimulation of the acetylcholine receptor, antioxidant genes, neurotrophic factors, and expression of NeuN, SYP, DCX, and ChAT.

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Ziprasidone attenuates brain injury after focal cerebral ischemia induced by middle cerebral artery occlusion in rats

Cited by 10 publications

References 52 publications

Administration of Mesenchymal Stem Cells and Ziprasidone Enhanced Amelioration of Ischemic Brain Damage in Rats

Administration of Mesenchymal Stem Cells and Ziprasidone Enhanced Amelioration of Ischemic Brain Damage in Rats

Post-Stroke Mortality, Stroke Severity, and Preadmission Antipsychotic Medicine Use – A Population-Based Cohort Study

Effects of Rice Bran Extracts Fermented with Lactobacillus plantarum on Neuroprotection and Cognitive Improvement in a Rat Model of Ischemic Brain Injury

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