Protective Effect of Carnosine on Subcortical Ischemic Vascular Dementia in Mice

Ma, Jing; Xiong, Jie; Hou, Weiwei; Yan, Haijing; Sun, Yungang; Huang, Shangwei; Jin, Le; Wang, Ye; Chen, Zhong

doi:10.1111/j.1755-5949.2012.00362.x

Cited by 59 publications

(60 citation statements)

References 45 publications

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“…Several previous reports showed that carnosine also had beneficial activities in neurodegenerative diseases including Alzheimer diseases, 61 and dementia. 62 Of note, dysregulation of autophagic processes have been recently recognized to contribute to the progress of these neurodegenerative diseases. 63,64 Further elucidation of carnosine's effects on autophagy in these neurodegenerative diseases is needed.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Mitochondrial Function and Autophagy Mediates Carnosine Neuroprotection Against Ischemic Brain Damage

Baek

Noh

Kim

et al. 2014

Stroke

155

104

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Background and Purpose Despite the rapidly increasing global burden of ischemic stroke, no therapeutic options for neuroprotection against stroke currently exist. Recent studies have shown that autophagy plays a key role in ischemic neuronal death and treatments that target autophagy may represent a novel strategy in neuroprotection. We investigated whether autophagy is regulated by carnosine, an endogenous pleiotropic dipeptide which has robust neuroprotective activity against ischemic brain damage. Methods We examined the effect of carnosine on mitochondrial dysfunction and autophagic processes in rat focal ischemia and in neuronal cultures. Results Autophagic pathways such as reduction of phosphorylated mTOR/p70S6K and the conversion of LC3-I to LC3-II were enhanced in the ischemic brain. However, treatment with carnosine significantly attenuated autophagic signaling in the ischemic brain, with improvement of brain mitochondrial function and mitophagy signaling. The protective effect of carnosine against autophagy was also confirmed in primary cortical neurons. Conclusion Taken together, our data suggest that the neuroprotective effect of carnosine is at least partially mediated by mitochondrial protection, and attenuation of deleterious autophagic processes. Our findings shed new light on the mechanistic pathways that this exciting neuroprotective agent influences.

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Section: Discussionmentioning

confidence: 99%

Modulation of Mitochondrial Function and Autophagy Mediates Carnosine Neuroprotection Against Ischemic Brain Damage

Baek

Noh

Kim

et al. 2014

Stroke

155

104

View full text Add to dashboard Cite

show abstract

“…[55][56][57] In mice treated with right unilateral common carotid arteries occlusion (rUCCAO), an animal model for SVID, microglia in the corpus callosum were also found to be activated as the number of ionizing calcium-binding adaptor molecule 1 (Iba-1) positive microglia was greatly increased. 58 Treatment of carnosine (β-alanyl-L-histidine), a natural dipeptide highly expressed in CNS, resulted in microglial deactivation and ameliorated cognitive impairment and white matter lesion in these mice. These results also support that early classical activation of microglia contributes to demyelination at the early stages of white matter diseases.…”

Section: Iver S E Ac Tivati On Of MI Crog Lia In White Mat Ter-rementioning

confidence: 99%

Heterogeneity of microglia and their differential roles in white matter pathology

Lee

Hamanaka

et al. 2019

CNS Neurosci Ther

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Microglia are resident immune cells that play multiple roles in central nervous system (CNS) development and disease. Although the classical concept of microglia/macrophage activation is based on a biphasic beneficial‐versus‐deleterious polarization, growing evidence now suggests a much more heterogenous profile of microglial activation that underlie their complex roles in the CNS. To date, the majority of data are focused on microglia in gray matter. However, demyelination is a prominent pathologic finding in a wide range of diseases including multiple sclerosis, Alzheimer's disease, and vascular cognitive impairment and dementia. In this mini‐review, we discuss newly discovered functional subsets of microglia that contribute to white matter response in CNS disease onset and progression. Microglia show different molecular patterns and morphologies depending on disease type and brain region, especially in white matter. Moreover, in later stages of disease, microglia demonstrate unconventional immuno‐regulatory activities such as increased phagocytosis of myelin debris and secretion of trophic factors that stimulate oligodendrocyte lineage cells to facilitate remyelination and disease resolution. Further investigations of these multiple microglia subsets may lead to novel therapeutic approaches to treat white matter pathology in CNS injury and disease.

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“…Recent research showed that carnosine reduces brain damage after ischemic stroke by preserving the normal glutathione levels and decreasing matrix metalloproteinase levels and activity36. Furthermore, carnosine can suppress myelin degeneration in mice after unilateral common carotid arteries occlusion37. Therefore, given that CEGI contains both these components, CEGI might be more potent and effective than either component alone.…”

Section: Discussionmentioning

confidence: 99%

Cattle encephalon glycoside and ignotin reduced white matter injury and prevented post-hemorrhagic hydrocephalus in a rat model of intracerebral hemorrhage

Zhao

et al. 2016

Sci Rep

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The morbidity, mortality, and disability associated with intraventricular hemorrhage (IVH) secondary to intracerebral hemorrhage (ICH) represent a global burden. To date, there is no effective therapy for ICH other than supportive care. In this study, we assessed the neuroprotective effects of Cattle encephalon glycoside and ignotin (CEGI) injection in a rat model of ICH with ventricular extension (IVH/ICH). The IVH/ICH rat model was induced via injection of type IV collagenase in the caudate nucleus of Sprague-Dawley rats. The experimental animals were randomized to receive CEGI, monosialotetrahexosyl ganglioside (GM-1), or normal saline. The modified Garcia scale, corner turn test, immunofluorescence staining for myelin basic protein (MBP) and microtubule associated protein 2 (MAP-2), transmission electron microscopy (TEM), and magnetic resonance imaging were employed to evaluate the neuroprotective effect of CEGI in the IVH/ICH rat model. CEGI treatment significantly alleviated the neurobehavioral dysfunction, reduced the lateral ventricular enlargement, promoted hematoma absorption, effectively up-regulated MBP/MAP-2 expression, and ameliorated white matter fiber damage post-ICH induction. Our results demonstrate that CEGI has significant neuroprotective effects in a rat model of IVH/ICH. Therefore, it can be used as a candidate drug for the clinical treatment of IVH/ICH.

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Protective Effect of Carnosine on Subcortical Ischemic Vascular Dementia in Mice

Abstract: These data suggest that the neuroprotective effect of carnosine on rUCCAO in mice is not dependent on the histaminergic pathway, but may be due to a suppression of reactive oxygen species generation, glia activation, and myelin degeneration.

Cited by 59 publications

References 45 publications

Modulation of Mitochondrial Function and Autophagy Mediates Carnosine Neuroprotection Against Ischemic Brain Damage

Modulation of Mitochondrial Function and Autophagy Mediates Carnosine Neuroprotection Against Ischemic Brain Damage

Heterogeneity of microglia and their differential roles in white matter pathology

Cattle encephalon glycoside and ignotin reduced white matter injury and prevented post-hemorrhagic hydrocephalus in a rat model of intracerebral hemorrhage

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