acid-phosphatase and Ischemic-Attack--Transient

Though the potential use of adenosine as a neuroprotective agent has long been realized, there are currently no adenosine-based therapies for the prevention or treatment of cerebral ischemia and reperfusion injury. Prostatic acid phosphatase (PAP), an enzyme that has long served as a diagnostic marker for prostate cancer, has been recently demonstrated to exhibit ecto-5'-nucleotidase activity, and dephosphorylate endogenous extracellular AMP to adenosine. We therefore tested the hypothesis that PAP has sustained and potent neuroprotective effects against cerebral ischemia in the rat model of middle cerebral artery occlusion. We found that hPAP produced significant neuroprotection against focal cerebral ischemia, as evident from significant reduction in cerebral infarction and neurological deficits. The therapeutic time window for hPAP in rat focal cerebral ischemia model was limited from 6 h before ischemia to 1.5 h after reperfusion. The present study suggested that PAP is a potential candidate for the prevention and treatment of cerebral ischemic injury, especially during perioperative period.

Topics: 5'-Nucleotidase; Acid Phosphatase; Adenosine; Animals; Brain Damage, Chronic; Carotid Stenosis; Drug Evaluation, Preclinical; Enzyme Therapy; Humans; Infarction, Middle Cerebral Artery; Injections, Intraventricular; Ischemic Attack, Transient; Male; Neuroprotective Agents; Perioperative Period; Protein Tyrosine Phosphatases; Random Allocation; Rats; Rats, Sprague-Dawley

This investigation was conducted in rat brain tissues to elucidate the free radical induced cellular and subcellular membrane injuries in two different depth of global ischemia. Global moderate (penumbral) ischemia was performed on rat brains by bilateral vertebral arteries cauterization and temporary occlusion of the bilateral carotid arteries. Global severe ischemia was produced by a neck tourniquet in addition to four vessel occlusion. Somatosensory evoked potentials (SSEPs) were used as a feed back parameter to monitor electrophysiologically the ischemia. At the end of ischemic insult (0 min reperfusion) or various reperfusion periods (20, 60 and 240 min), all rats were decapitated and brains were frozen in liquid nitrogen. The brain tissues were prepared for the determination of cathepsin L (CL) and acid phosphatase (AP) activities in the supernatant (cytosolic) fraction (SF) and the fraction enriched with lysosomes (FEL). Further the level of thiobarbituric acid reactive substances (TBARS) of lipid peroxidation was assessed by the spectrophotometric methods. Severe ischemia-reperfusion was accompanied by a significant increase in TBARS levels and the SF/FEL ratio for CL and AP activities compared to the sham operated group and the concurrent reperfusion groups of moderate ischemia (p<0.05). There were no significant differences between the sham operated and moderate ischemia-reperfusion groups for the same parameters. Our data clearly demonstrate that; in rat brain although severe ischemia-reperfusion causes lipid peroxidation in cellular membranes and redistribution of lysosomal enzymes from lysosomes to cytoplasm due to lysosomal membrane injury, there are no changes in lysosomal membrane stability in moderate ischemia-reperfusion.

Topics: Acid Phosphatase; Animals; Blood Pressure; Brain; Cathepsin L; Cathepsins; Cysteine Endopeptidases; Endopeptidases; Evoked Potentials, Somatosensory; Ischemic Attack, Transient; Lipid Peroxidation; Lysosomes; Male; Prosencephalon; Rats; Reperfusion; Thiobarbituric Acid Reactive Substances; Time Factors

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Brain; Cerebral Hemorrhage; Cerebrovascular Disorders; Electron Transport Complex IV; Female; Glycogen; Histocytochemistry; Humans; Ischemia; Ischemic Attack, Transient; Leukocytes; Male; Middle Aged; Peroxidases

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Aspartic Acid; Dextrans; Electron Transport Complex IV; Female; Glycogen; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Leukocytes; Male; Middle Aged; Peroxidases; Potassium Magnesium Aspartate

Topics: Acid Phosphatase; Animals; Cerebral Cortex; Cytoplasmic Granules; Disease Models, Animal; Endoplasmic Reticulum; Golgi Apparatus; Haplorhini; Ischemic Attack, Transient; Lysosomes; Microscopy, Electron; Microscopy, Fluorescence; Mitochondrial Swelling; Nissl Bodies; Ribosomes

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Brain; Cats; Cerebral Arteries; Cerebrovascular Disorders; Dihydrolipoamide Dehydrogenase; Electron Transport Complex IV; Esterases; Female; Glucosyltransferases; Ischemic Attack, Transient; L-Lactate Dehydrogenase; Male; Oxidoreductases; Phosphoric Monoester Hydrolases; Staining and Labeling; Succinate Dehydrogenase

Topics: Acid Phosphatase; Animals; Brain; Cerebral Cortex; Cerebrovascular Disorders; Disease Models, Animal; Glucuronidase; Glycogen; Hemiplegia; Hydrolases; Hypoxia; Hypoxia, Brain; Ischemic Attack, Transient; Lysosomes; Male; Mitochondria; Rats

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adrenal Cortex Hormones; Adrenocortical Hyperfunction; Alkaline Phosphatase; Animals; Aorta, Thoracic; Arteries; Biological Transport, Active; Blood Pressure; Calcium; Coronary Vessels; Esterases; Histocytochemistry; Hyperplasia; Hypertension; Hypertrophy; Ischemic Attack, Transient; Kidney; Malate Dehydrogenase; Male; Mesenteric Arteries; Methods; Organ Size; Potassium; Rabbits; Sodium; Succinate Dehydrogenase