Cyclo-prolylalanine: the neuroprotective and antioxidative properties on the model of acute cerebral disease in rats

2016 ◽  
Vol 14 (4) ◽  
pp. 16-23
Author(s):  
Roman D Deiko ◽  
Sergii Yu Shtrygol ◽  
Alexandr A Kolobov ◽  
Andrey S Simbirtsev
Keyword(s):  
Cognitive Deficits ◽  
Open Field Test ◽  
Reduced Glutathione ◽  
Cerebral Disease ◽  
Reference Drug ◽  
Antioxidative Properties ◽  
Bilateral Carotid Occlusion ◽  
Bilateral Carotid ◽  
Activity Decrease ◽  
The Brain

The neuroprotective and antioxidative properties of the new neuroactive peptide cyclo-prolylalanine (DKP-9) were studied on the model of acute cerebral disease (ACD, irreversible bilateral carotid occlusion) in rats. Under the conditions of intranasal administration in the therapeutic mode at the doses 0.02 mg/kg or 0.1 mg/kg peptide DKP-9 has increased rats’ survival rate to 40% or 70% respectively. Increase of the DKP-9 dose to 1 mg/kg reduced the protective effect of it. Peptide DKP-9 has effective decreased the neurological and cognitive deficits in acute period of ACD (4 days) exceeding the reference drug semax (0.1 mg/kg, intranasally in same treatment mode). Under the conditions of open-field test the sedative properties of DKP-9 and also the ability of it to reduce rats’ stress-induced anxious reactions were established. Antioxidative properties of DKP-9 are followed by increase of the reduced glutathione level, normalize of the catalase activity, decrease of the level of lipid peroxidation products as well as increase of the brain neurons’ energy metabolism. The further investigation of mechanism of cyclo-prolylalanine (DKP-9) action on the pathogenic links of ischemic cascade is perspective.

Differential Effects of Anesthetic Agents on Outcome from Near-complete but Not Incomplete Global Ischemia in the Rat 

1998 ◽  
Vol 89 (2) ◽  
pp. 391-400 ◽  
Author(s):  
Yoshihide Miura ◽  
Hilary P. Grocott ◽  
Robert D. Bart ◽  
Robert D. Pearlstein ◽  
Franklin Dexter ◽  
...  
Keyword(s):  
Carotid Occlusion ◽  
Ca1 Neurons ◽  
Differential Effects ◽  
Anesthetic Agents ◽  
Bilateral Carotid Occlusion ◽  
Hippocampal Ca1 ◽  
Bilateral Carotid ◽  
Cerebral Ischemic ◽  
The Brain ◽  
Incomplete Ischemia

Background It has been postulated that anesthetic agents that reduce cerebral metabolic rate will protect the brain against ischemia when electroencephalographic (EEG) activity is persistent, but will provide no protection when ischemia is severe enough to cause EEG isoelectricity. No outcome studies have addressed this issue. The authors studied anesthetic agents to determine if they provide differential effects on outcome from global cerebral ischemic insults that cause either an attenuated or isoelectric EEG. Methods Fasted rats were subjected to either (1) incomplete ischemia (attenuated EEG; 20 min of mean arterial pressure [MAP] = 50 mmHg and bilateral carotid occlusion) or (2) near-complete ischemia (isoelectric EEG; 10 min of MAP = 30 mmHg and bilateral carotid occlusion) while anesthetized with 1.4% isoflurane, 1 mg x kg(-1) x min(-1) ketamine, or 25 microg x kg(-1) x h(-1) 70% nitrous oxide and fentanyl. The brain was maintained at normothermia during ischemia and for 22 h after ischemia. Five days later, hippocampal CA1 and cortical injury were measured. Results There was no difference among anesthetic agents during incomplete ischemia for mean +/- SD percentage dead CA1 neurons (fentanyl, 38%+/-20%; isoflurane, 31%+/-10%; ketamine, 40%+/-19%; P = 0.38). During near-complete ischemia, there was a difference among anesthetic agents (fentanyl, 88%+/-9%; isoflurane, 37%+/-20%; ketamine, 70%+/-28%; P = 0.00008). Isoflurane was protective compared with fentanyl (P = 0.00007) and ketamine (P = 0.0061). There was no difference between fentanyl and ketamine (P = 0.143). Similar observations were made in the cortex. Neurologic function correlated with histologic damage. Conclusions Outcome from near-complete but not incomplete cerebral ischemia depended on the anesthetic agent administered during the ischemic insult.

scholarly journals Attenuation of Ischemia-Induced Extracellular Adenosine Accumulation by Homocysteine

1993 ◽  
Vol 13 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Veronica M. Sciotti ◽  
David G. L. Van Wylen
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Interstitial Fluid ◽  
Homocysteine Thiolactone ◽  
Early Reperfusion ◽  
Extracellular Adenosine ◽  
Arterial Blood ◽  
Bilateral Carotid Occlusion ◽  
Bilateral Carotid ◽  
The Brain

The purpose of this study was to determine the effects of homocysteine, which consumes intracellular adenosine via formation of S-adenosylhomocysteine, on interstitial fluid (ISF) adeonsine and cerebral blood flow (CBF) before, during, and after cerebral ischemia. Microdialysis probes, used to measure local CBF (H2 clearance) and to sample ISF, were implanted bilaterally into the caudate nucleus of halothane-anesthetized rats ( n = 8). l-Homocysteine thiolactone was administered locally via one of the probes. Animals were exposed to 20 min of ischemia, induced by bilateral carotid occlusion plus hemorrhage to an arterial blood pressure of 50 mm Hg, followed by 60 min of reperfusion. Before ischemia, CBF and dialysate adenosine were decreased with homocysteine. During ischemia and early reperfusion, dialysate purine metabolites increased on both sides of the brain; however, the ischemia-induced increase in adenosine was attenuated on the side of local homocysteine. CBF was lower on the side of homocysteine throughout reperfusion. These data demonstrate that homocysteine (a) decreases basal ISF adenosine and CBF, (b) attenuates the increase in dialysate adenosine during ischemia, and (c) reduces hyperemia during early reperfusion.

scholarly journals Corrective influence of ademol on metabolism of nitrogen monoxide in the brain of the rats with modeling cerebral ischemia

2014 ◽  
Vol 18 (1 (69)) ◽  
Author(s):  
O. A. Khodakovskiy ◽  
A. Y. Khodakovskiy
Keyword(s):  
Cerebral Ischemia ◽  
Nitrogen Monoxide ◽  
Carotid Occlusion ◽  
Treatment Mode ◽  
Bilateral Carotid Occlusion ◽  
Bilateral Carotid ◽  
The Brain ◽  
Better Than

In experiments on the rats with model of acute disorder of encephalic circulation (bilateral carotid occlusion) it was established that introduction of derivate of adamantan 1-adamantilethyloxy-3-morpholino-2 propanol hydrochloride (under conventional name ademol) in dose 2 mg/kg intraabdominal in treatment mode (in an hour after insult and further 1 time a day after every 24 hours during 21 days of cerebral ischemia) better than cerebroprotector citicoline provides decreasing of activity of general NOsynthase (NOS) in the rats’ brain, on which indicated reduced content of stable metabolite of NO and preservation of L-arginine (L-Arg) pool. Such effect of ademol can be one of the key mechanisms of its protective influence on ischemic neurons of the brain and indicate a perspective for creation on its base a new cerebroprotector agent.

scholarly journals Inhibition of Poly(ADP-Ribose) Polymerase Suppresses Inflammation and Promotes Recovery after Ischemic Injury

2009 ◽  
Vol 29 (4) ◽  
pp. 820-829 ◽  
Author(s):  
Tiina M Kauppinen ◽  
Sang Won Suh ◽  
Ari E Berman ◽  
Aaron M Hamby ◽  
Raymond A Swanson
Keyword(s):  
Inflammatory Responses ◽  
Parp Inhibitor ◽  
Parp Inhibition ◽  
Bilateral Carotid Occlusion ◽  
Hippocampal Ca1 ◽  
Bilateral Carotid ◽  
Ca1 Area ◽  
The Brain ◽  
Parp 1

The brain inflammatory response induced by stroke contributes to cell death and impairs neurogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1) is a coactivator of the transcription factor NF-κB and required for NF-κB-mediated inflammatory responses. Here we evaluated PARP inhibition as a means of suppressing post-stroke inflammation and improving outcome after stroke. Rats were subjected to bilateral carotid occlusion-reperfusion, and treatment with the PARP inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)- N,N-dimethylacetamide (PJ34) was begun 48 h later. PJ34 was found to rapidly suppress the ischemia-induced microglial activation and astrogliosis. Behavioral tests performed 6 to 8 weeks after ischemia showed deficits in spatial memory and learning that were lessened by the PJ34 treatment. Immunohistochemical evaluation of hippocampus at 8 weeks after ischemia showed increased neuronal density in CA1 layer of PJ34-treated animals relative to vehicle-treated animals. Bromodeoxyuridine labeling showed formation of new neurons in hippocampal CA1 area in PJ34-treated animals, but not in vehicle-treated animals. Together, these results suggest that treatment with a PARP inhibitor for several days after ischemia enhances long-term neuronal survival and neurogenesis by reducing inflammation.

scholarly journals The influence of ademol on the indices of energy metabolism in the rat brain with a model of acute cerebral ischemia

2013 ◽  
Vol 17 (2 (66)) ◽  
pp. 140-142
Author(s):  
O. A. Khodakivskyi
Keyword(s):  
Energy Metabolism ◽  
Cerebral Ischemia ◽  
Rat Brain ◽  
Cerebral Circulation ◽  
Treatment Mode ◽  
Bilateral Carotid Occlusion ◽  
Acute Cerebral Ischemia ◽  
Bilateral Carotid ◽  
The Brain ◽  
Better Than

In experiments on rats with a model acute disorder of the cerebral circulation (bilateral carotid occlusion) it has been established that the introduction of a derivative adamantane 1-adamantiletiloxy-3-morpholino-2 propanol hydrochloride (under a conventional name ademol) in a dose of 2 mg/kg intraabdominally in the treatment mode (in an hour after insult and further 1 time per diem in every 24 hours during 4 days of cerebral ischemia) better than the cerebral protector cytikolin contributes to a decrease of disorders of carbohydrate and energy metabolism. A similar effect of ademol is one of the key mechanisms of its protective influence on ischemized neurons of the brain, pointing out to its perspective for the creation on its basis of a new cerebroprotective agent.

Morphological Changes in the Brain of Acutely Ill and Weight-Recovered Patients with Anorexia Nervosa

2014 ◽  
Vol 42 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Jochen Seitz ◽  
Katharina Bühren ◽  
Georg G. von Polier ◽  
Nicole Heussen ◽  
Beate Herpertz-Dahlmann ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Cognitive Deficits ◽  
Time Course ◽  
Morphological Changes ◽  
Meta Analysis ◽  
Short Term ◽  
Clinical Prognosis ◽  
Qualitative Review ◽  
Brain Changes ◽  
The Brain

Objective: Acute anorexia nervosa (AN) leads to reduced gray (GM) and white matter (WM) volume in the brain, which however improves again upon restoration of weight. Yet little is known about the extent and clinical correlates of these brain changes, nor do we know much about the time-course and completeness of their recovery. Methods: We conducted a meta-analysis and a qualitative review of all magnetic resonance imaging studies involving volume analyses of the brain in both acute and recovered AN. Results: We identified structural neuroimaging studies with a total of 214 acute AN patients and 177 weight-recovered AN patients. In acute AN, GM was reduced by 5.6% and WM by 3.8% compared to healthy controls (HC). Short-term weight recovery 2–5 months after admission resulted in restitution of about half of the GM aberrations and almost full WM recovery. After 2–8 years of remission GM and WM were nearly normalized, and differences to HC (GM: –1.0%, WM: –0.7%) were no longer significant, although small residual changes could not be ruled out. In the qualitative review some studies found GM volume loss to be associated with cognitive deficits and clinical prognosis. Conclusions: GM and WM were strongly reduced in acute AN. The completeness of brain volume rehabilitation remained equivocal.

Abstract MP17: Upregulating E2F1 Mitigates Senescence-Associated Phenotypes in Cultured Primary Endothelial Cells

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Michael E Maniskas ◽  
Yun-ju Lai ◽  
Sean P Marrelli ◽  
Louise D McCullough ◽  
Jose F Moruno-manchon
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Neurovascular Unit ◽  
Glucose Deprivation ◽  
Cerebral Hypoperfusion ◽  
Aged Mouse ◽  
Aged Mice ◽  
Brain Vasculature ◽  
Bilateral Carotid ◽  
The Brain

Vascular contributions to cognitive impairment and dementia (VCID) includes multiple disorders that are identified by cognitive deficits secondary to cerebrovascular pathology. The risk of VCID is higher in people after the age of 70, and, currently, there is no effective treatment. Vascular endothelial cells (VEC) are critical components of the brain vasculature and neurovascular unit and their health is vital to the capacity of the brain vasculature to respond to stressors. However, aged VEC may enter an irreversible replicative-arrest state (senescence), which has been associated with dementia. E2F transcription factor 1 (E2F1) regulates cell cycle progression and DNA damage repair. Importantly, E2F1 deficiency is associated with cell senescence. We hypothesized that E2F1 downregulation contributes to senescence in the cerebral endothelium during aging. We used cultured primary VEC from young (4-months old, mo) and aged (18-mo) male and female mice for RNA sequencing, plasmid-based gene delivery, high-resolution microscopy, and (4-, 12-, and 18-mo) mice of the bilateral carotid artery stenosis (BCAS) model, which produces chronic cerebral hypoperfusion and recapitulates some of the features seen in patients with VCID. We found that overexpression of E2F1 reduced the levels of senescence-associated phenotypes in cultured VEC from young mice that were exposed to oxygen and glucose deprivation (p<0.001), which induces endothelial senescence. Our RNA seq data showed that the expression of E2f1 was reduced (~40%) in cultured primary VEC from aged mouse brains compared with young cells (p<0.001). E2F1 levels were reduced in the brains of aged mice. Interestingly, we found sex differences in E2F1 levels, with less protein levels (~30%) in males vs females (p<0.05), independently of age. Also, aged BCAS mice (1 month after surgery) had more severe senescence phenotypes, reduced cerebral blood flow, and worse memory deficits compared with control mice (p<0.05). The effect of BCAS was more prominent in aged mice compared with younger (4- and 12-mo) mice. In conclusion , our study identifies E2F1 as a potential regulator of endothelial senescence in mice and highlights the contribution of aging as an important factor in losing endothelial resilience.

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