fumarates and Cerebrovascular-Disorders

Topics: Aged; Benzyl Compounds; Cerebrovascular Disorders; Clinical Trials as Topic; Cycloheptanes; Digitalis Glycosides; Drug Therapy, Combination; Evaluation Studies as Topic; Fumarates; Humans; Memory Disorders; Middle Aged; Propylamines; Vascular Headaches; Vertigo

Topics: Age Factors; Aged; Blood Pressure; Capillary Resistance; Central Nervous System; Cerebrovascular Disorders; Clinical Trials as Topic; Cycloheptanes; Diffuse Cerebral Sclerosis of Schilder; Electroencephalography; Female; Fumarates; Humans; Lipid Metabolism; Male; Middle Aged; Oscillometry; Parasympatholytics; Propylamines; Vital Capacity

The aim of the study was to investigate neuroprotective effect of creatine glycine ethylic ether fumarate (creamide). The methods involved intragastric administration of creamide in doses of 30 and 50 mg/kg twice a day for 10 days. Focal 30 minutes cerebral ischemia model by endovascular suture occlusion of the middle cerebral artery in a rat with subsequent reperfusion period for 48 hours was produced. Assessment of creamide stability in gastric juice was performed. Ischemic lesion volume accompanying focal ischemia was visualized and determined. Similar infarction patterns had been found with histological methods. Garcia scale was used for clinical study of neurological deficit in rats. Our data suggest a significant neuroprotective effect of creamide in dosage 50 mg/kg administered twice a day which decreased brain lesion volume produced by ischemic and reperfusion injury.

Topics: Animals; Cerebrovascular Disorders; Disease Models, Animal; Fumarates; Male; Middle Cerebral Artery; Neuroprotective Agents; Rats; Reperfusion Injury

Pre-treatment with angiotensin receptor blockers is known to improve neurological outcome after stroke. This study investigated for the first time, whether the renin inhibitor aliskiren has similar neuroprotective effects.. Since aliskiren specifically blocks human renin, double transgenic rats expressing human renin and angiotensinogen genes were used. To achieve a systolic blood pressure of 150 or 130 mmHg animals were treated with aliskiren (7.5 or 12.5 mg/kg*d) or candesartan (1.5 or 10 mg/kg*d) via osmotic minipump starting five days before middle cerebral artery occlusion with reperfusion. Infarct size was determined by magnetic resonance imaging. mRNA of inflammatory marker genes was studied in different brain regions.. The mortality of 33.3% (7 of 21 animals) in the vehicle group was reduced to below 10% by treatment with candesartan or aliskiren (p<0.05). Aliskiren-treated animals had a better neurological outcome 7 days post-ischemia, compared to candesartan (Garcia scale: 9.9±0.7 vs. 7.3±0.7; p<0.05). The reduction of infarct size in the aliskiren group did not reach statistical significance compared to candesartan and vehicle (24 h post-ischemia: 314±81 vs. 377±70 and 403±70 mm(3) respectively). Only aliskiren was able to significantly reduce stroke-induced gene expression of CXC chemokine ligand 1, interleukin-6 and tumor necrosis factor-alpha in the ischemic core.. Head-to-head comparison suggests that treatment with aliskiren before and during cerebral ischemia is at least as effective as candesartan in double transgenic rats. The improved neurological outcome in the aliskiren group was blood pressure independent. Whether this effect is due to primary anti-inflammatory mechanisms has to be investigated further.

Topics: Amides; Angiotensinogen; Animals; Animals, Genetically Modified; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Brain; Brain Ischemia; Cerebral Arterial Diseases; Cerebrovascular Disorders; Chemokine CXCL1; Fumarates; Gene Expression; Humans; Interleukin-6; Rats; Renin; Reverse Transcriptase Polymerase Chain Reaction; Stroke; Tetrazoles; Tumor Necrosis Factor-alpha

Topics: Adult; Aged; Cerebrovascular Disorders; Female; Fumarates; Humans; Ischemia; Male; Middle Aged; Vascular Diseases

Topics: Adolescent; Adult; Aged; Autonomic Nervous System; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Cycloheptanes; Fumarates; Headache; Humans; Injections, Intra-Arterial; Middle Aged; Parasympatholytics; Propylamines; Respiratory Tract Diseases; Spasm; Tranquilizing Agents; Ulcer; Vascular Diseases; Vascular Resistance

Topics: Aged; Arteriosclerosis Obliterans; Blood Circulation; Cerebrovascular Disorders; Cycloheptanes; Diabetic Angiopathies; Fumarates; Humans; Male; Middle Aged; Neurotic Disorders; Nicotinic Acids; Oscillometry; Papaverine; Parasympatholytics; Propylamines; Regional Blood Flow; Skin Temperature; Theophylline; Thromboangiitis Obliterans; Thrombosis; Tranquilizing Agents; Vascular Diseases

Topics: Aged; Arteriosclerosis; Cerebrovascular Circulation; Cerebrovascular Disorders; Cycloheptanes; Eye Diseases; Female; Fumarates; Humans; Male; Middle Aged; Neuritis; Ophthalmodynamometry; Papaverine; Parasympatholytics; Propylamines; Vascular Diseases; Vasodilator Agents

Topics: Blood Flow Velocity; Cerebrovascular Circulation; Cerebrovascular Disorders; Cycloheptanes; Fumarates; Humans; Parasympatholytics; Propylamines; Regional Blood Flow

Topics: Aged; Cerebrovascular Circulation; Cerebrovascular Disorders; Cycloheptanes; Female; Fumarates; Humans; Middle Aged; Oxygen Consumption; Vasodilator Agents