Reduction of the infarct size by simultaneous administration of l-histidine and diphenhydramine in ischaemic rat brains

Adachi, Naoto; Liu, Keyue; Ninomiya, Kanji; Matsuoka, Eiko; Motoki, Atsuko; Irisawa, Yumi; Nishibori, Masahiro

doi:10.1016/j.resuscitation.2010.10.024

Cited by 6 publications

(4 citation statements)

References 9 publications

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“…, the acute excitotoxicity and inflammatory infiltration usually take place within one week after the onset of ischemia, whereas the glial scar formation and neurogenesis often appears after that 1 . Thus, at first we experimented the doses of histidine (200, 500, or 1000 mg/kg) during the first week, which are often selected dosages in the study of cerebral ischemia 11 15 16 . We found that the highest dose provided the most prominent protection as evidenced by the neurological deficit score ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Histidine provides long-term neuroprotection after cerebral ischemia through promoting astrocyte migration

Liao

Jiang

Wang

et al. 2015

Sci Rep

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The formation of glial scar impedes the neurogenesis and neural functional recovery following cerebral ischemia. Histamine showed neuroprotection at early stage after cerebral ischemia, however, its long-term effect, especially on glial scar formation, hasn’t been characterized. With various administration regimens constructed for histidine, a precursor of histamine, we found that histidine treatment at a high dose at early stage and a low dose at late stage demonstrated the most remarkable long-term neuroprotection with decreased infarct volume and improved neurological function. Notably, this treatment regimen also robustly reduced the glial scar area and facilitated the astrocyte migration towards the infarct core. In wound-healing assay and transwell test, histamine significantly promoted astrocyte migration. H2 receptor antagonists reversed the promotion of astrocyte migration and the neuroprotection provided by histidine. Moreover, histamine upregulated the GTP-bound small GTPase Rac1, while a Rac1 inhibitor, NSC23766, abrogated the neuroprotection of histidine and its promotion of astrocyte migration. Our data indicated that a dose/stage-dependent histidine treatment, mediated by H2 receptor, promoted astrocyte migration towards the infarct core, which benefited long-term post-cerebral ischemia neurological recovery. Therefore, targeting histaminergic system may be an effective therapeutic strategy for long-term cerebral ischemia injury through its actions on astrocytes.

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Section: Resultsmentioning

confidence: 99%

Histidine provides long-term neuroprotection after cerebral ischemia through promoting astrocyte migration

Liao

Jiang

Wang

et al. 2015

Sci Rep

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“…At least in the guinea pig heart and pig hearts, HMT was detected earlier ( Tahara et al, 2000 ; Klocker et al, 2005 ). HMT can be inhibited by diphenhydramine and other histamine receptor antagonists which might pose problems in data interpretation ( Adachi et al, 2011 ). In the rat brain, HMT inhibitors could increase the levels of histamine in vivo ( Duch et al, 1978 ), but which is difficult to compare with our present findings.…”

Section: Discussionmentioning

confidence: 99%

Histamine can be Formed and Degraded in the Human and Mouse Heart

et al. 2021

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Histamine is metabolized by several enzymes in vitro and in vivo. The relevance of this metabolism in the mammalian heart in vivo is unclear. However, histamine can exert positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H2-histamine receptors. In transgenic mice (H2-TG) that overexpress the human H2 receptor in cardiomyocytes but not in wild-type littermate mice (WT), histamine induced PIE and PCE in isolated left or right atrial preparations. These H2-TG were used to investigate the putative relevance of histamine degrading enzymes in the mammalian heart. Histidine, the precursor of histamine, increased force of contraction (FOC) in human atrial preparations. Moreover, histamine increased the phosphorylation state of phospholamban in human atrium. Here, we could detect histidine decarboxylase (HDC) and histamine itself in cardiomyocytes of mouse hearts. Moreover, our data indicate that histamine is subject to degradation in the mammalian heart. Inhibition of the histamine metabolizing enzymes diamine oxidase (DAO) and monoamine oxidase (MAO) shifted the concentration response curves for the PIE in H2-TG atria to the left. Moreover, activity of histamine metabolizing enzymes was present in mouse cardiac samples as well as in human atrial samples. Thus, drugs used for other indication (e.g. antidepressants) can alter histamine levels in the heart. Our results deepen our understanding of the physiological role of histamine in the mouse and human heart. Our findings might be clinically relevant because we show enzyme targets for drugs to modify the beating rate and force of the human heart.

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“…Several studies have also examined the involvement of histaminergic circuits in carnosine-induced neuroprotection in ischemic stroke. Acute administration of L-histidine in combination with diphenhydramine (an inhibitor of histamine-inactivating enzyme in the brain) reduced infarct size by 25% and improved ischemia-induced brain edema [71]. Favourable effects of L-histidine administration were observed immediately, after 6 hours, and after 24 h upon acute brain ischemic injury [72].…”

Section: Animal Studies Of the Role Of Carnosine In Brain-related mentioning

confidence: 99%

The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence

Schön

Mousa²,

Berk

et al. 2019

Nutrients

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Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological presence of this di-peptide and its analogues in the brain together with their ability to cross the blood-brain barrier as well as evidence from in vitro, animal, and human studies suggest carnosine as a promising therapeutic target in brain disorders. In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.

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Reduction of the infarct size by simultaneous administration of l-histidine and diphenhydramine in ischaemic rat brains

Cited by 6 publications

References 9 publications

Histidine provides long-term neuroprotection after cerebral ischemia through promoting astrocyte migration

Histidine provides long-term neuroprotection after cerebral ischemia through promoting astrocyte migration

Histamine can be Formed and Degraded in the Human and Mouse Heart

The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence

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