losartan-potassium and Central-Nervous-System-Diseases

Erythropoietin (EPO) is an exciting neurotherapeutic option. Despite its potential, concerns exist regarding the potential for thrombosis and adverse events with EPO administration in normonemic adults. Systematic review of literature using PRISMA guidelines to examine the application and risks of EPO as a treatment option for neuroprotection in normonemic adults. Independent, systematic searches were performed in July 2019. PubMed (1960-2019) and the Cochrane Controlled Trials Register (1960-2019) were screened. Search terms included erythropoietin, neuroprotection, and humans. The PubMed search resulted in the following search strategy: ("erythropoietin" [MeSH Terms] OR "erythropoietin" [All Fields] OR "epoetin alfa" [MeSH Terms] OR ("epoetin" [All Fields] AND "alfa" [All Fields]) OR "epoetin alfa" [All Fields]) AND ("neuroprotection" [MeSH Terms] OR "neuroprotection" [All Fields]) AND "humans" [MeSH Terms]. PubMed, Cochrane Controlled Trials Register, and articles based on prior searches yielded 388 citations. 50 studies were included, comprising of 4351 patients. There were 13 studies that noted adverse effects from EPO. Three attributed serious adverse effects to EPO and complications were statistically significant. Two of these studies related the adverse events to the co-administration of EPO with tPA. Minor adverse effects associated with the EPO group included nausea, pyrexia, headache, generalized weakness and superficial phlebitis. Most published studies focus on spinal cord injury, peri-surgical outcomes and central effects of EPO. We found no studies to date evaluating the role of EPO in post-operative pain. Future trials could evaluate this application in persistent post-surgical pain and in the peri-operative period.

Topics: Central Nervous System Diseases; Erythropoietin; Humans; Neuroprotection; Neuroprotective Agents; Optic Neuritis; Peripheral Nervous System Diseases

Erythropoietin (EPO) is a growth hormone and cytokine that plays an important role in erythropoiesis and neuroprotection. However, EPO treatment for neurological diseases requires repeated injections or high-dose systemic administration, which may cause systemic side effects. The lack of any effective treatment of acute and chronic neurodegenerative diseases and the promising outcome by EPO in animal models in vivo demand a critical evaluation of intranasal EPO delivery to the brain as an alternative administration method.. The current use and intranasal administration of EPO and its derivatives in preclinical studies and recent clinical trials with EPO in neurological diseases.. This paper gives an overview of the therapeutic considerations of intranasal EPO and EPO derivatives for neuroprotection.. Intranasal delivery (ID) of neuroprotective drugs is an area of great interest. Among the administration strategies used at present, ID of EPO is the most promising. Further preclinical and clinical studies are needed to evaluate the potential significance of this alternative route for increasing EPO bioavailability and decreasing side effects.

Topics: Administration, Intranasal; Animals; Brain; Central Nervous System Diseases; Disease Models, Animal; Drug Delivery Systems; Erythropoietin; Humans; Neuroprotective Agents

Recombinant human erythropoietin (epoetin) has become the standard of care in the treatment of anaemia resulting from cancer and its treatment, and chronic kidney disease. The discovery that erythropoietin and its receptor are located in regions outside the erythropoietic system has led to interest in the potential role of epoetin in other tissues, such as the central nervous system. Animal studies have shown that systemically applied epoetin can cross the blood-brain barrier, where it reduces tissue injury associated with stroke, blunt trauma and experimental autoimmune encephalomyelitis. Pilot studies in humans have shown that epoetin treatment given within 8 h of stroke reduces infarct size and results in a significantly better outcome when compared with placebo treatment. Studies also suggest that epoetin has the potential to improve cognitive impairment associated with adjuvant chemotherapy in patients with cancer. Anaemia is a major factor causing tumour hypoxia, a condition that can promote changes within neoplastic cells that further tumour survival and malignant progression and also reduces the effectiveness of several anticancer therapies including radiotherapy and oxygen-dependent cytotoxic agents. Use of epoetin to prevent or correct anaemia has the potential to reduce tumour hypoxia and improve treatment outcome. Several therapeutic studies in anaemic animals with experimental tumours have shown a beneficial effect of epoetin on delaying tumour growth. Furthermore, clinical observations in patients with multiple myeloma and animal studies have suggested that epoetin has an antimyeloma effect, mediated via the immune system through activation of CD8+ T cells. Therefore, the role of epoetin may go well beyond that of increasing haemoglobin levels in anaemic patients, although additional studies are required to confirm these promising results.

Topics: Anemia, Hypochromic; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Hypoxia; Central Nervous System Diseases; Chemotherapy, Adjuvant; Cognition; Erythropoietin; Humans; Multiple Myeloma; Neoplasms; Pilot Projects; Recombinant Proteins

Erythropoietin (EPO) primarily is produced in the kidney and acts as a principal mediator of the physiologic response to hypoxia by increasing red blood cell production. Astrocytes and neurons in the central nervous system (CNS) also are known to produce EPO in response to hypoxia/ischemia. EPO appears to play a neuroprotective role based on preclinical data demonstrating the ability of recombinant human erythropoietin (r-HuEPO) to shield neurons from hypoxic/ischemic stress when administered intracerebraventricularly. In CNS models, systemically administered r-HuEPO has not been intensely investigated because large glycosylated molecules generally were deemed incapable of crossing the blood-brain barrier (BBB). A collaborative research effort identified expression of EPO receptors on human brain capillaries and a specific receptor-mediated transport of r-HuEPO across the BBB after a single intraperitoneal (IP) injection in rodents, with subsequent protection against various types of neuronal damage. For example, administration of r-HuEPO 24 hours before or up to 6 hours after focal ischemic stroke significantly reduced the extent of infarction. r-HuEPO also attenuated concussive brain injury, kainate-induced seizure activity, and autoimmune encephalomyelitis. These preclinical findings suggest that r-HuEPO may have therapeutic potential for stroke, head trauma, and epilepsy; additional studies are needed to confirm and extend these encouraging observations in animal models.

Topics: Animals; Central Nervous System Diseases; Disease Models, Animal; Erythropoiesis; Erythropoietin; Humans; Recombinant Proteins

Topics: Animals; Blood Viscosity; Cardiovascular Diseases; Central Nervous System Diseases; Erythrocyte Deformability; Erythropoietin; Female; Fetal Hypoxia; Fetofetal Transfusion; Fetomaternal Transfusion; Fetus; Follow-Up Studies; Gastrointestinal Diseases; Genital Diseases, Male; Global Health; Growth Disorders; Hematocrit; Humans; Hyperbilirubinemia; Hypocalcemia; Hypoglycemia; Infant, Newborn; Infant, Small for Gestational Age; Kidney Diseases; Male; Mental Disorders; Polycythemia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy in Diabetics; Prognosis; Respiration Disorders; Sheep; Thrombocytopenia

Topics: Animals; Central Nervous System Diseases; Erythropoiesis; Erythropoietin; Female; Genes, Regulator; Genital Diseases, Female; Hemodynamics; Humans; Hypertension; Hypoxia; Kidney; Kidney Diseases; Liver Diseases; Male; Polycythemia; Polycythemia Vera; Rats

Erythropoietin (EPO) plays a critical role in the development of the nervous system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic protein (GFAP) levels in the serum were determined and water content of brain and the extravasation of a tracer (Evans blue) were measured. Brain lipid peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2 protein relative expressions were determined. Cation exchange chromatography was used to evaluate MBP alterations. Seven days after exposure, pathological assessment was performed after Klüver-Barrera staining. EPO reduced malondialdehyde levels at all doses (2500, 5000 and 10,000 u/kg). Lower doses of EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of GFAP. EPO could not reduce the water content of the edematous poisoned brains. However, at 5000 and 10,000 u/kg it protected the blood brain barrier against integrity loss as a result of CO. EPO could significantly decrease the MPO activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO could partially prevent these biochemical changes. Fewer vacuoles and demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced it 38.86%. These results reveal that EPO could relatively prevent different pathways of neurotoxicity by CO poisoning and thus has the potential to be used as a novel approach to manage this poisoning.

Topics: Animals; bcl-2-Associated X Protein; Blood-Brain Barrier; Brain; Carbon Monoxide; Carbon Monoxide Poisoning; Central Nervous System Diseases; Dose-Response Relationship, Drug; Erythropoietin; Gene Expression Regulation; Lipid Peroxidation; Male; Myelin Basic Protein; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Rats; Rats, Wistar

Topics: Brain Injuries; Central Nervous System Diseases; Erythropoietin; Humans; Neuroprotective Agents; Receptors, Erythropoietin; Recombinant Proteins

Topics: Animals; Central Nervous System Diseases; Erythropoietin; Heart Arrest, Induced

Current data suggest that erythropoietin protects the brain and the spinal cord from ischemic and traumatic injury. In this study, we determined whether erythropoietin protects the central nervous system during prolonged hypothermic circulatory arrest in an experimental canine model.. Ten adult beagle dogs were randomly and intravenously injected with either 5000 U/kg recombinant human erythropoietin or normal saline. Each dog was then subjected to a cardiopulmonary bypass and 120 minutes of deep hypothermic circulatory arrest (18 degrees C). The level of tau proteins in the cerebrospinal fluid, a modified marker of neurologic deficit in dogs, and the histopathologic characteristics of the brains and spinal cords were then examined.. The level of tau proteins was significantly lower in the erythropoietin-treated group than in the untreated group at 6 hours (20 +/- 12 vs 144 +/- 54 pg/mL; P = .036) and 12 hours (64 +/- 35 vs 478 +/- 103 pg/mL; P = .01) after the operation. The total Neurologic Deficit Score was 59 +/- 31 (0, normal; 500, brain death) in the erythropoietin-treated group, compared with 376 +/- 30 in the untreated group (P = .0117). Histopathologic examination revealed that ischemic neuronal changes and apoptosis in the hippocampus CA1 were significantly lower in the erythropoietin-treated group (P < .01 and P = .028, respectively).. This study showed that erythropoietin protected the central nervous system during prolonged hypothermic circulatory arrest, partly by preventing both necrosis (ischemic neuronal changes) and apoptosis.

Topics: Animals; Central Nervous System Diseases; Dogs; Erythropoietin; Female; Heart Arrest, Induced; Male; Recombinant Proteins; Time Factors

Erythropoietin (Epo) is a glycoprotein secreted by the kidney in response to hypoxia that stimulates erythropoiesis through interaction with cell surface Epo receptors. Pre-treatment with Epo has been shown to protect neurons in models of ischemic injury. The mechanism responsible for this neuroprotection and the effects of Epo on astroglial and other non-neuronal cell populations remain unknown. In the present study, we determined whether Epo pre-treatment protects neonatal rat astrocytes from apoptotic cell death resulting from treatment with nitric oxide, staurosporine (STS) and arsenic trioxide and possible mechanisms mediating Epo-related cytoprotection. Epo (5-20 U/mL) significantly attenuated multiple hallmarks of apoptotic cell death in astroglia exposed to nitric oxide and STS but not arsenic trioxide. Epo (20 U/mL) induced mild oxidative stress as shown by increases in heme oxygenase (HO)-1 mRNA and protein expression that could be suppressed by antioxidant coadministration. Moreover, coincubation with tin-mesoporphyrin, a competitive inhibitor of HO activity, abrogated the cytoprotective effects of Epo (20 U/mL) in the face of STS treatment. Thus, induction of the ho-1 gene may contribute to the glioprotection accruing from high-dose Epo exposure. Epo may augment astroglial resistance to certain chemical stressors by oxidative stress-dependent and -independent mechanisms.

Topics: Animals; Apoptosis; Astrocytes; Cell Hypoxia; Cells, Cultured; Central Nervous System Diseases; Cytoprotection; Erythropoietin; Ischemic Preconditioning; Neurodegenerative Diseases; Rats; Rats, Sprague-Dawley

Anemia is a multifactorial problem in patients with human immunodeficiency virus (HIV) infection, cancer, and hepatitis C virus (HCV) infection. New insights regarding anemia symptoms and quality of life (QOL) have prompted reassessment of traditional triggers for anemia treatment to increase hemoglobin (Hb) and improve QOL. In HIV-positive patients, anemia is independently associated with disease progression and survival. Many HIV-positive patients receiving highly active antiretroviral therapy (HAART) still develop mild to moderate anemia and associated QOL impairment. Epoetin alfa effectively increases Hb and improves QOL in these patients. Many HIV-positive patients are coinfected with HCV. Standard HCV therapy (interferon alfa/ribavirin) can cause anemia that may result in treatment alterations and compromised virologic outcome. Epoetin alfa therapy in anemic HCV patients increases Hb levels and may provide other benefits. Neuroprotective effects of epoetin alfa in preclinical models of central nervous system disorders have recently been demonstrated, implying a new therapeutic role for this cytokine.

Topics: Anemia; Central Nervous System Diseases; Epoetin Alfa; Erythropoietin; Hepacivirus; Hepatitis C; HIV; HIV Infections; Humans; Neoplasms; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical models of CNS disorders. Epoetin alfa has also been shown to prevent the loss of autoregulation of cerebral blood flow in a model of subarachnoid hemorrhage. The mechanisms of EPO-induced neuroprotection include prevention of glutamate-induced toxicity, inhibition of apoptosis, anti-inflammatory effects, antioxidant effects, and stimulation of angiogenesis. Collectively, these findings suggest that epoetin alfa may have potential therapeutic utility in patients with ischemic CNS injury.

Topics: Anemia; Central Nervous System; Central Nervous System Diseases; Clinical Trials as Topic; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Neuroprotective Agents; Recombinant Proteins

Topics: Central Nervous System Diseases; Cerebellar Neoplasms; Diencephalon; Erythropoiesis; Erythropoietin; Hemangiosarcoma; Humans; Hypoxia; Polycythemia

Topics: Adolescent; Adult; Animals; Biological Assay; Central Nervous System Diseases; Cerebellar Neoplasms; Erythropoiesis; Erythropoietin; Female; Hemangiosarcoma; Hematocrit; Humans; Iron Isotopes; Male; Mice; Teratoma