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

1995 ◽  
pp. 26-33 ◽  
Author(s):  
Hirosuke Fujisawa ◽  
Hans Landolt ◽  
Ross Bullock
Keyword(s):  
Brain Damage ◽  
In Vivo Model ◽  
Basic Study ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Glutamate Neurotoxicity

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

2008 ◽  
Vol 30 (5) ◽  
pp. 313-320 ◽  
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

scholarly journals Reduction of Ischemic Brain Damage by Nitrous Oxide and Xenon

2003 ◽  
Vol 23 (10) ◽  
pp. 1168-1173 ◽  
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.

scholarly journals Melatonin Protects Against Ischemic Brain Injury by Modulating PI3K/AKT Signaling Pathway via Suppression of PTEN Activity

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110228
Author(s):  
Yuanyuan Ran ◽  
Lin Ye ◽  
Zitong Ding ◽  
Fuhai Gao ◽  
Shuiqing Yang ◽  
...  
Keyword(s):  
Brain Damage ◽  
Neuronal Cell ◽  
Akt Signaling ◽  
In Vivo Model ◽  
Neuronal Membrane ◽  
Melatonin Treatment ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Akt Phosphorylation ◽  
Akt Activation

Stroke is one of the leading causes of death and disability worldwide with limited therapeutic options. Melatonin can attenuate ischemic brain damage with improved functional outcomes. However, the cellular mechanisms of melatonin-driven neuroprotection against post-stroke neuronal death remain unknown. Here, distal middle cerebral artery occlusion (dMCAO) was performed in C57BL/6j mice to develop an ischemic stroke in vivo model. Melatonin was injected intraperitoneally immediately after ischemia, and 24 and 48 hours later. Melatonin treatment, with 5 to 20 mg/kg, elicited a dose-dependent decrease in infarct volume and concomitant increase in sensorimotor function. At the molecular level, phosphorylation of PTEN and Akt were increased, whereas PTEN activity was decreased in melatonin treated animals 72 hours after dMCAO. At the cellular level, oxygenglucose deprivation (OGD) challenge of neuronal cell line Neuro-2a (N2a) and primary neurons supported melatonin’s direct protection against neuronal cell death. Melatonin treatment reduced LDH release and neuronal apoptosis at various time points, markedly increased Akt phosphorylation in neuronal membrane, but significantly suppressed it in the cytoplasm of post-OGD neurons. Mechanistically, melatonin-induced Akt phosphorylation and neuronal survival was blocked by Wortmannin, a potent PIP3 inhibitor, exposing increased PI3K/Akt activation as a central player in melatonin-driven neuroprotection. Finally, PTEN knock-down through siRNA significantly inhibited PI3K/Akt activation and cell survival following melatonin treatment, suggesting that melatonin protection against ischemic brain damage, is at least partially, dependent on modulation of the PTEN/PI3K/Akt signaling axis.

scholarly journals TERT Promotes Neurogenesis and Neural Repair after Hypoxic Ischemic Brain Damage in Neonatal Rats

2021 ◽  
Author(s):  
Jiao Li ◽  
Hai-ting Liu ◽  
Jing Zhao ◽  
Zhi Fang
Keyword(s):  
Developmental Stage ◽  
Brain Damage ◽  
Neurological Function ◽  
Cell Counting ◽  
Neonatal Rats ◽  
Ischemic Brain Damage ◽  
Neural Repair ◽  
Ischemic Brain

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.

Felbamate reduces hypoxic-ischemic brain damage in vivo

1992 ◽  
Vol 212 (2-3) ◽  
pp. 275-278 ◽  
Author(s):  
Claude G. Wasterlain ◽  
Lisa M. Adams ◽  
Haruo Hattori ◽  
Phillip H. Schwartz
Keyword(s):  
Brain Damage ◽  
Ischemic Brain Damage ◽  
Ischemic Brain
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