Brain Factor-7® improves learning and memory deficits and attenuates ischemic brain damage by reduction of ROS generation in stroke in vivo and in vitro

Abstract Neonatal hypoxic ischemic encephalopathy (HIE) endangers quality of life in children; but effective cure is rare. Neurogenesis plays an important role in neural repair following brain damage. Recent studies have demonstrated that telomerase reverse transcriptase (TERT) was involved in neurogenesis regulation. However, whether TERT participates in the regulation of neurogenesis after hypoxic-ischemic brain damage (HIBD) is unclear. Here, we established a model of HIBD in neonatal rats both in vivo and in vitro, and used lentivirus and adenovirus transfection for TERT overexpression to investigate its role in neurogenesis after HIBD in developmental stage. Using immunofluorescence staining, cell counting Kit-8 staining, TUNEL, and western blotting, we observed that TERT attenuated apoptosis and promoted proliferation, migration, and differentiation in neural stem cells (NSCs). Furthermore, TERT induced myelination in the brain of neonatal rats after HIBD. Neurobehavioral tests revealed that TERT could improve learning, memory, and neurological function after HIBD in neonatal rats, and thus promote the recovery of neurological function after HIBD. In addition, we investigated the regulatory mechanism of TERT during neurogenesis after HIBD in developmental stage. We found that TERT may regulate neurogenesis after HIBD through the Sonic Hedgehog/Gli1 signaling pathway. Our study demonstrated that TERT could promote neural repair and neurological function recovery after HIBD in neonatal rats. The new neuroprotective pathway regulated by TERT during HIBD described here could provide a basis for developing therapeutic strategy for neonatal HIE. Furthermore, TERT may be a potential target during neural repair and reconstruction in various diseases affecting nervous system.

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Kiwifruit Alleviates Learning and Memory Deficits Induced by Pb through Antioxidation and Inhibition of Microglia Activation In Vitro and In Vivo

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/5645324 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 9

Author(s):

Wei-Zhen Xue ◽

Qian-Qian Yang ◽

Yiwen Chen ◽

Rong-Xin Zou ◽

Dong Xing ◽

...

Keyword(s):

Vitamin C ◽

Learning And Memory ◽

Cognitive Dysfunction ◽

Memory Deficits ◽

Postnatal Life ◽

Lactation Period ◽

Pb Exposure ◽

Learning And Memory Deficits

Lead (Pb) exposure, in particular during early postnatal life, increases susceptibility to cognitive dysfunction and neurodegenerative outcomes. The detrimental effect of Pb exposure is basically due to an increasing ROS production which overcomes the antioxidant systems and finally leads to cognitive dysfunction. Kiwifruit is rich in the antioxidants like vitamin C and polyphenols. This study aims to investigate the effects and mechanism of kiwifruit to alleviate learning and memory deficits induced by Pb exposure. Sprague-Dawley (SD) rat pups acquired Pb indirectly through their mothers during lactation period and after postnatal day 21 (PND21) directly acquired Pb by themselves. Five kinds of kiwifruits were collected in this study and the amounts of vitamin C and polyphenols in them were measured and the antioxidation effects were determined. Among them, Qinmei kiwifruit (Qm) showed the strongest antioxidation effects in vitro. In vivo, Qm significantly repaired Pb-induced learning and memory deficits and dendritic spine loss. In addition, Pb compromised the enzymatic activity and transcriptional levels of SOD and GSH-Px and decreased the microglial activation, which, to some extent, could be reversed by Qm kiwifruit administration. The results suggest that kiwifruit could alleviate Pb-induced cognitive deficits possibly through antioxidative stress and microglia inactivation. Consequently, kiwifruit could be potentially regarded as the functional food favorable in the prevention and treatment of Pb intoxication.

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Glutamate Neurotoxicity As a Mechanism of Ischemic Brain Damage: A Basic Study Using a New In Vivo Model

Neurochemical Monitoring in the Intensive Care Unit ◽

10.1007/978-4-431-68522-7_2 ◽

1995 ◽

pp. 26-33 ◽

Cited By ~ 1

Author(s):

Hirosuke Fujisawa ◽

Hans Landolt ◽

Ross Bullock

Keyword(s):

Brain Damage ◽

In Vivo Model ◽

Basic Study ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Glutamate Neurotoxicity

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The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic–ischemic brain damage in mice is mediated by CB2 and adenosine receptors

Neurobiology of Disease ◽

10.1016/j.nbd.2009.10.023 ◽

2010 ◽

Vol 37 (2) ◽

pp. 434-440 ◽

Cited By ~ 120

Author(s):

A. Castillo ◽

M.R. Tolón ◽

J. Fernández-Ruiz ◽

J. Romero ◽

J. Martinez-Orgado

Keyword(s):

Brain Damage ◽

Adenosine Receptors ◽

In Vitro Model ◽

Neuroprotective Effect ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Vitro Model

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Antisense in vivo knockdown of synaptotagmin I by HVJ–liposome mediated gene transfer attenuates ischemic brain damage in neonatal rats

Brain and Development ◽

10.1016/j.braindev.2007.08.002 ◽

2008 ◽

Vol 30 (5) ◽

pp. 313-320 ◽

Cited By ~ 6

Author(s):

Tadaki Omae ◽

Hiroshi Yoshioka ◽

Taro Tanaka ◽

Hideyuki Nagai ◽

Makoto Saji ◽

...

Keyword(s):

Gene Transfer ◽

Brain Damage ◽

Neonatal Rats ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Synaptotagmin I

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Reduction of Ischemic Brain Damage by Nitrous Oxide and Xenon

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/01.wcb.0000087342.31689.18 ◽

2003 ◽

Vol 23 (10) ◽

pp. 1168-1173 ◽

Cited By ~ 78

Author(s):

Helene N David ◽

Frederic Leveille ◽

Laurent Chazalviel ◽

Eric T MacKenzie ◽

Alain Buisson ◽

...

Keyword(s):

Nitrous Oxide ◽

Brain Damage ◽

Neuronal Death ◽

Cortical Cell ◽

Critical Event ◽

Neuroprotective Agents ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Neurotoxic Effects

Neuronal death after ischemia-induced brain damage depends largely upon the activation of the N-methyl-D-aspartate (NMDA) excitatory glutamate receptor that is a target for many putative neuroprotective agents. Whereas the NMDA receptors mediate ischemic brain damage, blocking them is deleterious in humans. Here, the authors investigated whether nitrous oxide or xenon, which are gaseous anesthetics with a remarkably safe clinical profile that have been recently demonstrated as effective inhibitors of the NMDA receptor, may reduce the following: (1) ischemia-induced brain damage in vivo, when given after occlusion of the middle cerebral artery (MCAO), a condition needed to make these potentially neuroprotective agents therapeutically valuable; or (2) NMDA-induced Ca2+ influx in cortical cell cultures, a major critical event involved in excitotoxic neuronal death. The authors have shown that both nitrous oxide at 75 vol% and xenon at 50 vol% reduce ischemic neuronal death in the cortex by 70% and further decrease NMDA-induced Ca2+ influx by 30%. In addition, xenon at 50%, but not nitrous oxide at 75 vol%, further decreases ischemic brain damage in the striatum (a subcortical structure that is known to be resistant to neuroprotective interventions). However, at a higher concentration (75 vol%), xenon exhibits potentially neurotoxic effects. The mechanisms of the neuroprotective and potentially neurotoxic effects of nitrous oxide and xenon, as well as the possible therapeutic implications in humans, are discussed.

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Spatial learning and memory deficits induced by prenatal glucocorticoid exposure depend on hippocampal CRHR1 and CXCL5 signaling in rats

Journal of Neuroinflammation ◽

10.1186/s12974-021-02129-8 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

You Zheng ◽

Yan-Min Zhang ◽

Zheng-Shan Tang ◽

Jian-Kui Du ◽

De-Wei Guo ◽

...

Keyword(s):

Learning And Memory ◽

Spatial Learning ◽

Memory Deficits ◽

Morris Water Maze Test ◽

Spatial Learning And Memory ◽

Synapsin I ◽

Postnatal Life ◽

Pregnant Rats ◽

Learning And Memory Deficits

Abstract Background Prenatal synthetic glucocorticoid (sGC) exposure increases the susceptibility to cognitive and affective disorders in postnatal life. We previously demonstrated that prenatal sGC exposure results in an increase in corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) expression in the hippocampus of rats, and CRHR1 is involved in synapse formation via regulation of C-X-C chemokine ligand 5 (CXCL5) in hippocampus. We sought to investigate that the roles of CRHR1 and CXCL5 in learning and memory impairment caused by prenatal sGC exposure. Methods Pregnant rats were administered with saline or dexamethasone (DEX) from gestational day (GD) 14 to GD21. DEX offspring at 2-day old were treated with saline and CRHR1 antagonists (antalarmin and CP154526) for 7 days. Some DEX offspring received intra-hippocampal injection of AAV9 carrying CXCL5 gene. Spatial learning and memory was assessed by Morris water maze test. Immunofluorescence analysis was applied to show synapsin I and PSD95 signals in hippocampus. Synapsin I and PSD95 protein level and CXCL5 concentration were determined by western blotting and ELISA, respectively. Organotypic hippocampal slice cultures were used to investigate the effect of DEX on CXCL5 production in vitro. Results Both male and female DEX offspring displayed impairment of spatial learning and memory in adulthood. Synapsin I and PSD95 signals and CXCL5 levels were decreased in DEX offspring. DEX offspring with antalarmin and CP154526 treatment showed improved spatial learning and memory. Antalarmin and CP154526 treatment increased synapsin I and PSD95 signals and CXCL5 concentration in hippocampus. Bilaterally hippocampal injection of AAV9 carrying CXCL5 gene improved the spatial learning and memory and increased CXCL5 concentration and synapsin I and PSD95 levels in hippocampus. DEX dose-dependently suppressed CXCL5 production in cultured hippocammpal slices, which was prevented by antalarmin treatment. Conclusion CRHR1 and CXCL5 signaling in the hippocampus are involved in spatial learning and memory deficits caused by prenatal DEX exposure. CRHR1 activation contributes to decreased CXCL5 production in hippocampus induced by prenatal DEX treatment. Our study provides a molecular basis of prenatal GC exposure programming spatial learning and memory.

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