scholarly journals Neural like cells and acetyl-salicylic acid alter rat brain structure and function following transient middle cerebral artery occlusion

2018 ◽  
Vol 9 (1) ◽  
pp. 155-168 ◽  
Author(s):  
Ali Shamsara ◽  
Vahid Sheibani ◽  
Majid Asadi-Shekaari ◽  
Seyed Noureddin Nematollahi-Mahani
Keyword(s):  
Cerebral Ischemia ◽  
Spatial Memory ◽  
Learning And Memory ◽  
Infarct Volume ◽  
Medical Intervention ◽  
Transient Cerebral Ischemia ◽  
Male Rats ◽  
Human Umbilical Cord ◽  
The Brain

AbstractIntroductionTransient cerebral ischemia is a pandemic neurological disorder and the main aim of medical intervention is to reduce complications. Human umbilical cord mesenchymal cells (hUCMs) are capable of differentiating into neural-like cells (NLC) in vitro, therefore we investigated the neuroprotective potential of these cells in comparison to aspirin and in combination (NLC-Aspirin) on spatial memory and neural morphologic changes in male rats submitted to transient cerebral ischemia.MethodsTen days after the intervention, the improvement in learning and memory were assessed in the animals by Morris Water Maze. Thence, the animals were examined for the presence of PKH26 labeled cells in the ischemic area of the brain, the infarct volume and neural changes in the brain tissue.ResultsSignificant spatial memory deficits in the ischemic animals were detected compared with the control animals. The learning and memory were significantly improved (p ≤ 0.05) in the aspirin and NLC groups compared with the ischemic animals. Co-treatment of aspirin and NLCs did not improve the outcome. Moreover, infarction volume and neural changes were significantly altered when aspirin or NLCs were administered.ConclusionsOur data suggest the significant neuroprotective potential of aspirin and neural-like cells derived from hUCM cells in the treatment of brain ischemic stroke. Further studies are required to evaluate possible underlying mechanisms, and to evaluate the possible interactions between aspirin and stem cells in a joint treatment aimed at the recovery of cognitive impairments

scholarly journals GABAB receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Song ◽  
Yaohua Chen ◽  
Cheng Chen ◽  
Lili Chen ◽  
Oumei Cheng
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurogenesis ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
In Vitro Experiments ◽  
Adult Mice

Abstract Purpose and background Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.

scholarly journals Zingiber officinaleMitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Jinatta Jittiwat ◽  
Terdthai Tongun ◽  
Supaporn Muchimapura ◽  
Kornkanok Ingkaninan
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Morris Water Maze Test ◽  
Brain Infarct ◽  
Ginger Rhizome ◽  
The Brain

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect ofZingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

scholarly journals Reappearance of Hippocampal CA1 Neurons after Ischemia is Associated with Recovery of Learning and Memory

2005 ◽  
Vol 25 (12) ◽  
pp. 1586-1595 ◽  
Author(s):  
Olof Bendel ◽  
Tjerk Bueters ◽  
Mia von Euler ◽  
Sven Ove Ögren ◽  
Johan Sandin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Cognitive Functions ◽  
Spatial Learning And Memory ◽  
Neuronal Marker ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 ◽  
The Brain

The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.

Protective effect of Oren-gedoku-to (Huang-Lian-Jie-Du-Tang) against impairment of learning and memory induced by transient cerebral ischemia in mice

2000 ◽  
Vol 73 (3) ◽  
pp. 405-413 ◽  
Author(s):  
Jinghua Xu ◽  
Yukihisa Murakami ◽  
Kinzo Matsumoto ◽  
Michihisa Tohda ◽  
Hiroshi Watanabe ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Protective Effect ◽  
Learning And Memory ◽  
Transient Cerebral Ischemia

scholarly journals Modulator of apoptosis-1 is a potential therapeutic target in acute ischemic injury

2018 ◽  
Vol 39 (12) ◽  
pp. 2406-2418 ◽  
Author(s):  
Su Jing Chan ◽  
Hui Zhao ◽  
Kazuhide Hayakawa ◽  
Chou Chai ◽  
Chong Teik Tan ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Infarct Volume ◽  
Neuronal Loss ◽  
Ischemic Injury ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
In Vivo Models ◽  
The Brain

Modulator of apoptosis 1 (MOAP-1) is a Bax-associating protein highly enriched in the brain. In this study, we examined the role of MOAP-1 in promoting ischemic injuries following a stroke by investigating the consequences of MOAP-1 overexpression or deficiency in in vitro and in vivo models of ischemic stroke. MOAP-1 overexpressing SH-SY5Y cells showed significantly lower cell viability following oxygen and glucose deprivation (OGD) treatment when compared to control cells. Consistently, MOAP-1−/− primary cortical neurons were observed to be more resistant against OGD treatment than the MOAP-1+/+ primary neurons. In the mouse transient middle cerebral artery occlusion (tMCAO) model, ischemia triggered MOAP-1/Bax association, suggested activation of the MOAP-1-dependent apoptotic cascade. MOAP-1−/− mice were found to exhibit reduced neuronal loss and smaller infarct volume 24 h after tMCAO when compared to MOAP-1+/+ mice. Correspondingly, MOAP-1−/− mice also showed better integrity of neurological functions as demonstrated by their performance in the rotarod test. Therefore, both in vitro and in vivo data presented strongly support the conclusion that MOAP-1 is an important apoptotic modulator in ischemic injury. These results may suggest that a reduction of MOAP-1 function in the brain could be a potential therapeutic approach in the treatment of acute stroke.

scholarly journals Neuronal expression of the mitochondrial protein prohibitin confers profound neuroprotection in a mouse model of focal cerebral ischemia

2017 ◽  
Vol 38 (6) ◽  
pp. 1010-1020 ◽  
Author(s):  
Anja Kahl ◽  
Corey J Anderson ◽  
Liping Qian ◽  
Henning Voss ◽  
Giovanni Manfredi ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Mitochondrial Protein ◽  
Motor Impairment ◽  
Cell Types ◽  
Viral Gene ◽  
Sensory Motor ◽  
The Brain

The mitochondrial protein prohibitin (PHB) has emerged as an important modulator of neuronal survival in different injury modalities . We previously showed that viral gene transfer of PHB protects CA1 neurons from delayed neurodegeneration following transient forebrain ischemia through mitochondrial mechanisms. However, since PHB is present in all cell types, it is not known if its selective expression in neurons is protective, and if the protection occurs also in acute focal ischemic brain injury, the most common stroke type in humans. Therefore, we generated transgenic mice overexpressing human PHB1 specifically in neurons (PHB1 Tg). PHB1 Tg mice and littermate controls were subjected to transient middle cerebral artery occlusion (MCAo). Infarct volume and sensory-motor impairment were assessed three days later. Under the control of a neuronal promoter (CaMKIIα), PHB1 expression was increased by 50% in the forebrain and hippocampus in PHB1 Tg mice. The brain injury produced by MCAo was reduced by 63 ± 11% in PHB1 Tg mice compared to littermate controls. This reduction was associated with improved sensory-motor performance, suggesting that the salvaged brain remains functional. Approaches to enhance PHB expression may be useful to ameliorate the devastating impact of cerebral ischemia on the brain.

scholarly journals Preparation, Characterization, Pharmacokinetics and Biodistribution of Baicalin-Loaded Liposome on Cerebral Ischemia-Reperfusion after i.v. Administration in Rats

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1747 ◽  
Author(s):  
Nan Li ◽  
Lingling Feng ◽  
Yujun Tan ◽  
Yan Xiang ◽  
Ruoqi Zhang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Zeta Potential ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion ◽  
The Brain

The dry root of Scutellaria baicalensis, has traditionally been applied in the treatment of cerebral ischemia in Chinese clinics. Baicalin (BA) is considered the key ingredient in it for the brain protection effects. The bioavailability of BA is very low because of its poor lipid and water solubility, which limits the therapeutic effects and clinical application. The aim of the present study was to develop a novel BA-loaded liposome (BA-LP) formulation to improve the drug lipophilicity and further to enhance the drug-concentration in the brain tissues. This study is also designed to investigate the pharmacokinetics of BA in the pathological conditions of stroke and evaluate the pharmacokinetic differences of BA caused by stroke after intravenous administration with BA and BA-LP. In this study, the novel BA-LP prepared in early stage were characterized by morphology, size, zeta potential, encapsulation rate and the in vitro release. The pharmacokinetics and biodistribution of BA and BA-LP were investigated by intravenous administration in rats with middle cerebral artery occlusion (MCAO) model and normal group respectively. BA-LP had a mean particle size of 160–190 nm, zeta potential of −5.7 mV, and encapsulation efficiency of 42 ± 1%. The BA-LP showed a sustained-release behavior, the in vitro drug-release kinetic model of BA-LP fit well with the biphasic dynamic model equation: Q = 1 − (60.12e0.56t − 59.08e0.0014t). Pharmacokinetic behavior in MCAO rats is not consistent with that of normal rats. The middle cerebral artery occlusion rats got higher Cmax and AUC0–t, which were about 1.5–2 times to normal rats both in BA and liposome groups. In addition, it got especially higher distribution in brain, while BA were not detected in brain tissues on normal rats. The Cmax and AUC0–t values were significantly greater with liposome than BA on both normal and MCAO rats. The tissue distribution behavior was significantly altered in the case of liposome administrated in comparison with BA, which the concentrations in the heart, liver, spleen, lungs and brain were all increased after administrated liposome, but decreased in kidneys. The TI values showed that the target of liposome was improved especially to heart, spleen and brain, and the brain’s target was higher in striatum and cerebellum. In conclusion, BA-LP might be a potential drug delivery system to improve the therapeutic efficacy of BA. In addition, these results also suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of BA.

scholarly journals Protection against focal ischemic injury to the brain by trans-sodium crocetinate

2010 ◽  
Vol 113 (4) ◽  
pp. 802-809 ◽  
Author(s):  
Hiroaki Manabe ◽  
David O. Okonkwo ◽  
John L. Gainer ◽  
Ryon H. Clarke ◽  
Kevin S. Lee
Keyword(s):  
Small Molecules ◽  
Tissue Oxygenation ◽  
Infarct Volume ◽  
Ischemic Injury ◽  
Neural Tissue ◽  
Male Rats ◽  
Effective Dosage ◽  
Ischemic Penumbra ◽  
Temporary Ischemia ◽  
The Brain

Object Ischemic injury is a potential complication in a variety of surgical procedures and is a particular impediment to the success of surgeries involving highly vulnerable neural tissue. One approach to limiting this form of injury is to enhance metabolic supply to the affected tissue. Trans-sodium crocetinate (TSC) is a carotenoid compound that has been shown to increase tissue oxygenation by facilitating the diffusivity of small molecules, such as oxygen and glucose. The present study examined the ability of TSC to modify oxygenation in ischemic neural tissue and tested the potential neuroprotective effects of TSC in permanent and temporary models of focal cerebral ischemia. Methods Adult male rats (330–370 g) were subjected to either permanent or temporary focal ischemia by simultaneous occlusion of both common carotid arteries and the left middle cerebral artery (3-vessel occlusion [3-VO]). Using the permanent ischemia paradigm, TSC was administered intravenously beginning 10 minutes after the onset of ischemia at 1 of 8 dosages, ranging from 0.023 to 4.580 mg/kg. Cerebral infarct volume was measured 24 hours after the onset of ischemia. The effect of TSC on infarct volume was also tested after temporary (2-hour) ischemia using a dosage of 0.092 mg/kg. In other animals undergoing temporary ischemia, tissue oxygenation was monitored in the ischemic penumbra using a Licox probe. Results Administration of TSC reduced infarct volume in a dose-dependent manner in the permanent ischemia model, achieving statistical significance at dosages ranging from 0.046 to 0.229 mg/kg. The most effective dosage of TSC in the permanent ischemia experiment (0.092 mg/kg) was further tested using a temporary (2-hour) ischemia paradigm. Infarct volume was reduced significantly by TSC in this ischemia-reperfusion model as well. Recordings of oxygen levels in the ischemic penumbra of the temporary ischemia model showed that TSC increased tissue oxygenation during vascular occlusion, but reduced the oxygen overshoot (hyperoxygenation) that occurs upon reperfusion. Conclusions The novel carotenoid compound TSC exerts a neuroprotective influence against permanent and temporary ischemic injury when administered soon after the onset of ischemia. The protective mechanism of TSC remains to be confirmed; however, the permissive effect of TSC on the diffusivity of small molecules is a plausible mechanism based on the observed increase in tissue oxygenation in the ischemic penumbra. This represents a form of protection based on “metabolic reflow” that can occur under conditions of partial vascular perfusion. It is particularly noteworthy that TSC could conceivably limit the progression of a wide variety of cellular injury mechanisms by blunting the ischemic challenge to the brain.

scholarly journals Naloxone Ameliorates Spatial Memory Deficits and Hyperthermia Induced by a Neurotoxic Methamphetamine Regimen in Male Rats

2019 ◽  
Vol 8 ◽  
pp. 1182 ◽  
Author(s):  
Solmaz Khalifeh ◽  
Mehdi Khodamoradi ◽  
Vahid Hajali ◽  
Hamed Ghazvini ◽  
Lelia Eliasy ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Spatial Memory ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Memory Impairment ◽  
Memory Performance ◽  
Poor Performance ◽  
Male Rats ◽  
Spatial Learning And Memory ◽  
Opiate Antagonist

Background: Methamphetamine (METH) as a synthetic psychostimulant is being increasingly recognized as a worldwide problem, which may induce memory impairment. On the other hand, it is well established that naloxone, an opiate antagonist, has some beneficial effects on learning and memory. The present research aimed at evaluating naloxone effects on spatial learning and memory impairment triggered by a neurotoxic regimen of METH in male rats. Materials and Methods: The animals received the subcutaneous (sc) regimen of METH (4×6 mg/kg at 2-h intervals), intraperitoneal (ip) naloxone (4×1 mg/kg at 2-h intervals), or normal saline at four events. The Nal-METH group of rats received four naloxone injections (1 mg/kg, ip) 30 min before each METH injection (6 mg/kg, sc) at 2-h intervals. Seven days later, they were evaluated for spatial learning and memory in the Morris Water Maze (MWM) task. Result: METH regimen induced hyperthermia, as well as a poor performance, in the acquisition and retention phases of the task, indicating spatial learning and memory impairment compared to the controls. Naloxone administration (1 mg/kg, ip) before each METH injection led to significant attenuations of both hyperthermia and METH adverse effects on the rat performance in the MWM task. Conclusion: The results revealed that pretreatment with the opiate antagonist naloxone could prevent METH adverse effects on body temperature and memory performance. It seems that the opioidergic system and hyperthermia may, at least partially, be involved in METH effects on spatial memory. [GMJ. 2019;8:e1182]

scholarly journals Ghrelin reduces cerebral ischemic injury in rats by reducing M1 microglia/macrophages

2022 ◽  
Vol 66 (1) ◽  
Author(s):  
Rong Tian ◽  
Gengsheng Mao
Keyword(s):  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Infarct Volume ◽  
Neurological Function ◽  
Tunel Staining ◽  
Triphenyltetrazolium Chloride ◽  
Ischemic Brain ◽  
Tnf Α ◽  
Ischemic Brain Tissue ◽  
The Brain

The purpose of this study was to investigate the effect of Ghrelin on the polarization of microglia/ macrophages after cerebral ischemia (CI) in rats. 60 wild-type SD rats were randomly divided into sham group, CI group, CI+Ghrelin group, 20 rats in each group. The modified Longa suture method was used to establish the middle cerebral artery occlusion (MCAO) model in rats. Before surgery, Ghrelin was injected subcutaneously (100μg/kg, twice a day) for 4 consecutive weeks. After modeling, neurological function scores were performed with three behavioral experiments: mNSS score, Corner test, and Rotarod test, to evaluate the recovery of neurological function after Ghrelin treatment. At the same time, the brain tissues were collected and stained with 2,3,5-triphenyltetrazolium chloride (TTC) to detect the cerebral infarct volume. RT-qPCR was used to detect the expression of TNF-α and IL-1β in the ischemic brain tissue, and the TUNEL staining was used to detect the apoptosis of brain tissue. Flow cytometry was used to detect the percentage of M1 type microglia/macrophages which were isolated by trypsin digestion of fresh cerebral cortex. Then, the Western blotting and immunofluorescence method were used to detect the phosphorylation level of AKT (P-AKT) and AKT. Compared with the CI group, the neurological function of the rats in the CI+Ghrelin group was dramatically improved, and the cerebral infarction area was dramatically reduced. At the same time, the expression of TNF-α and IL-1β in the ischemic brain tissue of rats in the CI+Ghrelin group decreased, and the apoptotic cells in the brain tissue also decreased. Compared with the CI treatment group, the activation of M1 microglia/macrophages in the cortex of the ischemic side of the infarct and the peri-infarct area in the CI+Ghrelin group was dramatically inhibited. At the same time, the ratio of P-AKT/AKT of the brain tissue in the CI+Ghrelin group was dramatically higher than that of the CI group. In the rat cerebral ischemia model, Ghrelin can promote the repair of brain damage and the recovery of neurological function after ischemia. Its mechanism may be related to activating AKT to selectively reduce M1 microglia/macrophages, reducing inflammation and cell apoptosis in brain tissue.

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