Study of the Neuroprotective Activity of a New Fumaric Acid Derivative

In a narrowing beam-walking test, on the 21st day after the occlusion of the middle cerebral artery, it was found that the succinic salt of diethylaminoethanol fumaric ester (PDES), at doses of 10 and 75 mg/kg, led to a statistically signifi cant decrease in the severity of sensorimotor defi cit of the anterior and posterior contralateral limbs of male rats under the conditions of cerebral ischemia. The test substance at a dose of 10 mg/kg reduced the volume of ischemic damage to the cerebral cortex of rats by 1.5 times. In terms of neuroprotective activity, the effect of the succinic salt of diethylaminoethanol fumaric ester at a dose of 10 mg/kg is comparable to that of Citicoline at a dose of 500 mg/kg.

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Neuroprotective Effect of the AMPA Receptor Antagonist LY-293558 in Focal Cerebral Ischemia in the Cat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1994.57 ◽

1994 ◽

Vol 14 (3) ◽

pp. 466-471 ◽

Cited By ~ 67

Author(s):

R. Bullock ◽

D. I. Graham ◽

S. Swanson ◽

J. McCulloch

Keyword(s):

Cerebral Ischemia ◽

Middle Cerebral Artery ◽

Receptor Antagonist ◽

Ampa Receptor ◽

Cerebral Artery ◽

Focal Cerebral Ischemia ◽

Neuroprotective Effect ◽

Ischemic Damage ◽

Physiological Variables ◽

Ampa Receptor Antagonist

The effects of the glutamate α-amino-3-hydroxy 5-methyl-4-isoxazole propionate (AMPA) receptor antagonist LY-293558 in reducing ischemic brain damage have been assessed in halothane-anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery, and the animals were killed 6 h later. The amount of early irreversible ischemic damage was assessed at 16 predetermined stereotactic planes by an observer blinded to treatment paradigm employed. Treatment with LY-293558 (15 mg/kg i.v., plus infusion of 7 mg/kg/h) initiated 30 min prior to middle cerebral artery occlusion reduced significantly (p < 0.02) the volume of ischemic damage (from 3,423 ± 212 mm3 of the cerebral hemisphere in vehicle-treated cats to 2,822 ± 569 mm3 in LY-293558-treated cats). The present data demonstrate that an AMPA receptor antagonist can reduce focal ischemic damage in a gyrencephalic species in which key physiological variables have been controlled and monitored throughout the postischemic period. These data provide additional support for the clinical evaluation of AMPA receptor antagonists in focal cerebral ischemia in humans.

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Protective Effect of the Glutamate Antagonist, MK-801 in Focal Cerebral Ischemia in the Cat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1988.18 ◽

1988 ◽

Vol 8 (1) ◽

pp. 138-143 ◽

Cited By ~ 316

Author(s):

E. Ozyurt ◽

D. I. Graham ◽

G. N. Woodruff ◽

J. McCulloch

Keyword(s):

Cerebral Ischemia ◽

Nmda Receptor ◽

Middle Cerebral Artery ◽

Brain Damage ◽

Cerebral Artery ◽

Focal Cerebral Ischemia ◽

Ischemic Damage ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Mk 801

The effects of the glutamate N-methyl-D aspartate (NMDA) receptor antagonist, MK-801, upon ischemic brain damage has been examined in anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery and the animals were killed 6 h later. The amount of early ischemic damage was assessed in coronal sections at 16 predetermined stereotactic planes. Pretreatment with MK-801 (5 mg/kg, i.v.), 30 min before occlusion of the middle cerebral artery significantly reduced the volume of ischemic damage (from 32.7 ± 4.0% of the cerebral hemisphere in vehicle-treated cats to 16.2 ± 4.5% in MK-801-treated cats). NMDA receptor antagonists that penetrate the blood-brain barrier, such as MK-801, merit further study as protective agents against ischemic brain damage.

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Increased Expression Of Toll-Like Receptor 2 Mrna Following Permanent Middle Cerebral Artery Occlusion In Rat: Role Of TRPV1 Receptors

Advances in Bioscience and Clinical Medicine ◽

10.7575/aiac.abcmed.ca1.68 ◽

2017 ◽

pp. 68

Author(s):

Amir Moghadam Ahmadi ◽

Mohammad Allahtavakoli ◽

Ali Shamsizadeh ◽

Ali Roohbakhsh ◽

Alireza Vakilian ◽

...

Keyword(s):

Cerebral Ischemia ◽

Middle Cerebral Artery ◽

Mrna Expression ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Artery Occlusion ◽

Male Rats ◽

Neurological Deficits ◽

Slip Ratio ◽

Cerebral Artery Occlusion

Background: Stroke is a major cause of mortality and long term disability in adults. TRPV1 has a pivotal role in neuroinflammation. Among TLRs, TLR2 significantly participate in induction of inflammation in brain. In this study, the effect of TRPV1 receptor agonist and antagonist on outcome and gene expression of TLR2 in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated.Methods: Forty male rats were assigned to the following groups: sham, vehicle )stroke), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and behavioral functions were assessed 1, 3, and 7 days after stroke. Infarct volume, brain edema and mRNA expression of TLR2 were also evaluated at the end of the study.Results: While stroke animals showed infarctions and behavioral functions, we did not observe any cerebral infarction and behavioral functions in sham-operated animals. AMG9810 decreased neurological deficits 7 days after cerebral ischemia (P<0.01). In the ledged beam-walking test, the slip ratio was increased following ischemia (*P < 0.05). AMG9810 improved this index in animals undergone stroke. However, capsaicin enhanced the slip ratio 3 and 7 days after cerebral ischemia (#P<0.05). TLR2) P<0.05(mRNA expression was elevated in ischemic rats. Conclusion: Our data indicate that pharmacological blockade of TRPV1 by AMG9810 attenuates behavioral function and mRNA expression of TLR2. Therefore, it might be useful as a potential target for the treatment of ischemic stroke.

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Evidence for a protective role played by the Na+/Ca2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats

Neuropharmacology ◽

10.1016/j.neuropharm.2003.09.015 ◽

2004 ◽

Vol 46 (3) ◽

pp. 439-448 ◽

Cited By ~ 78

Author(s):

Giuseppe Pignataro ◽

Anna Tortiglione ◽

Antonella Scorziello ◽

Lucia Giaccio ◽

Agnese Secondo ◽

...

Keyword(s):

Cerebral Ischemia ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Protective Role ◽

Artery Occlusion ◽

Male Rats ◽

Cerebral Artery Occlusion

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Immunohistochemical investigation of cerebral ischemia after middle cerebral artery occlusion in gerbils

Journal of Neurosurgery ◽

10.3171/jns.1987.67.3.0414 ◽

1987 ◽

Vol 67 (3) ◽

pp. 414-420 ◽

Cited By ~ 17

Author(s):

Kazumi Yamamoto ◽

Fumiharu Akai ◽

Toshiki Yoshimine ◽

Takehiko Yanagihara

Keyword(s):

Cerebral Cortex ◽

Cerebral Ischemia ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Reactive Astrocytes ◽

Global Cerebral Ischemia ◽

Neuronal Structure ◽

Ischemic Lesion ◽

Content Type ◽

Immunohistochemical Reaction

✓ Progression and recovery of ischemic and postischemic damage after occlusion of the middle cerebral artery and subsequent reperfusion were investigated in the gerbil. This study was performed by immunohistochemical reaction testing for tubulin and creatine kinase BB-isoenzyme to visualize the neuronal structure and by immunohistochemical reaction testing for astroprotein (an astrocyte-specific protein) to visualize reactive astrocytes. The earliest ischemic lesion became visible in the frontoparietal cortex after 7 minutes of ischemia as a laminar loss of the reaction for tubulin involving the neuropil, neuronal perikarya, and dendrites. The earliest lesion in the caudoputamen evolved after 30 minutes of ischemia. After reestablishment of cerebral circulation, the immunohistochemical ischemic lesions in the neuronal structure disappeared if the ischemic period was 10 minutes or less and partially disappeared even after ischemia for 15 minutes in the cerebral cortex, while the postischemic lesion in the caudoputamen disappeared even after ischemia for 15 minutes. Reactive astrocytes were detected in the cerebral cortex and caudoputamen as early as 24 hours after reperfusion, both in the areas with and without the neuronal lesions. No lesion was identified in the hippocampus or thalamus. This experimental model is suitable for investigation of rapidly progressive regional ischemia in the cerebral cortex and for comparison with other regional or global cerebral ischemia in the gerbil or other animal species.

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Gingko biloba Extract (EGb 761) Prevents Cerebral Ischemia-Induced p70S6 Kinase and S6 Phosphorylation

The American Journal of Chinese Medicine ◽

10.1142/s0192415x10008196 ◽

2010 ◽

Vol 38 (04) ◽

pp. 727-734 ◽

Cited By ~ 18

Author(s):

Phil-Ok Koh

Keyword(s):

Cerebral Cortex ◽

Brain Injury ◽

Cerebral Ischemia ◽

Infarct Volume ◽

Male Rats ◽

Ischemic Brain Injury ◽

Egb 761 ◽

Ischemic Brain ◽

P70s6 Kinase ◽

Gingko Biloba

EGb 761 is an extract of Gingko biloba that exhibits neuroprotective effects against cerebral ischemia. The mammalian target of rapamycin (mTOR) is a critical downstream effector of Akt and a central regulator of ribosomal biogenesis and protein synthesis. We investigated whether EGb 761 regulates Akt downstream targets, including mTOR, p70S6 kinase, and S6 phosphorylation. Adult male rats were treated with vehicle or EGb 761 (100 mg/kg) prior to middle cerebral artery occlusion (MCAO). Brains were collected at 24 hours after MCAO and the cerebral cortex regions were examined. We previously showed that EGb 761 significantly reduces infarct volume and decreases the number of TUNEL-positive cells in the cerebral cortex. Ischemic brain injury induces a decrease in Akt up-stream target, PDK1 phosphorylation. The levels of phospho-mTOR, phospho-p70S6 kinase, and phospho-S6 are subsequently decreased in regions affected by ischemic injury. However, EGb 761 prevented injury-induced decreases in these protein levels. We confirmed that EGb 761 inhibits injury-induced decreases in the number of positive cells for phospho-p70S6 kinase and phospho-S6. The results of this study provide evidence that EGb 761 protects neuronal cells against ischemic brain injury by preventing injury-induced decreases in p70S6 kinase and S6 phosphorylation.

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Rat’s behaviour in eight-arms maze after modeling of focal transient cerebral ischemia with subsequent activation of striatal microglia

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2018-17-2-92-96 ◽

2018 ◽

Vol 17 (2) ◽

pp. 92-96

Author(s):

M. E. Kolpakova ◽

I. A. Filchenko ◽

A. . Trajkovski ◽

D. L. Tcyba ◽

O. V. Kirik ◽

...

Keyword(s):

Cerebral Ischemia ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Ischemia Reperfusion ◽

Cognitive Disorders ◽

Transient Cerebral Ischemia ◽

Male Rats ◽

Left Middle Cerebral Artery ◽

Reperfusion Period ◽

Anaesthetized Rats

It is well known that cognitive disorders at cerebral ischemia-reperfusion are followed by neuronal death. The inflammation of nervous tissue occurs, but the role of microgliocytes in neuroprotection is poorly understood. The aim of our work was to study microgliocytes in rats with cognitive disorders in delayed postischemic period after focal transient cerebral ischemia. In an experiment we used male rats (n=15), weighing 200-250. The model of focal brain ischemia was performed in anaesthetized rats (intraperitonealy, chloralhydrate 450 mg/kg). Microsurgical introduction monofilament to the left middle cerebral artery was made by J. Koizumi technique. Time of middle cerebral artery (MCA) occlusion was 30 minutes with the subsequent reperfusion period. Testing in eight-arm maze was performed within seven days twice with a two-day interval during which each animal carried out a 5-minute session 3 times with a 3-minute interval. For identification of microgliocytes used polyclonal goat antibodies to Iba1 antigen. At behavior assessment in an eight-arm maze there were errors of working memory revealed and prolongation of time of task performance. Cognitive disorders at cerebral ischemia, perhaps, serve as the neuroinflammation indicator. Microglia is likely involved in mechanisms of neuroprotection and compensation for cognitive disorders.

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SUMO2/3 is Associated with Ubiquitinated Protein Aggregates in the Mouse Neocortex after Middle Cerebral Artery Occlusion

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.180 ◽

2014 ◽

Vol 35 (1) ◽

pp. 1-5 ◽

Cited By ~ 16

Author(s):

Karin Hochrainer ◽

Katherine Jackman ◽

Corinne Benakis ◽

Josef Anrather ◽

Costantino Iadecola

Keyword(s):

Cerebral Ischemia ◽

Middle Cerebral Artery ◽

Focal Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Artery Occlusion ◽

Ischemic Damage ◽

Ubiquitinated Protein ◽

Functional Roles ◽

Protein Ubiquitination ◽

Cerebral Artery Occlusion

Protein modifications cooperatively act to protect the proteome from cellular stress. Focal cerebral ischemia increases protein ubiquitination, resulting in formation of ubiquitin-rich aggregates. A concurrent elevation in small ubiquitin-related modifier (SUMO)-conjugated proteins has also been reported, but a potential connection to ubiquitin remains unexplored. Here we show that SUMO2/3 conjugates are present in postischemic ubiquitin-rich aggregates, physically associated with ubiquitin. The coaggregation of SUMO2/3 and ubiquitin is induced rapidly after ischemia, depends on reperfusion, and is also observed in the absence of ischemic damage. The association between SUMO and ubiquitin suggests overlapping functional roles after ischemia/reperfusion.

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