tretinoin and Nervous-System-Diseases

Inflammation in the central nervous system (CNS) may occur as a result of trauma, infection or neurodegenerative stimuli and is characterized by activation of microglia, the resident immune cells of the CNS. Activated microglia proliferate rapidly, migrate to the site of injury or infection and elicit immune response by phagocytosis of cell debris, production of cytokines, chemokines and reactive oxygen species, and presentation of antigens to other immune cells. In addition, microglia participate in tissue repair by producing neurotrophic factors. However, when microglia are chronically activated, they become neurotoxic to the surrounding CNS parenchyma. Chronic activation of microglia has been shown to augment neurodegeneration in Parkinson's disease (PD), Alzheimer's disease (AD), brain injury and number of other CNS pathologies. Identification of factors that control microglial activation, therefore, has become the major focus of recent research. A number of herbal and chemical compounds have been shown to attenuate microglial activation. However, these compounds exhibit non-specificity and produce unpleasant side-effects. Here, we provide a comprehensive review on some of the currently available drugs known to reduce microglial activation, their molecular targets and the subcellular signaling networks on which they act. We also review some of the newly emerging therapeutic avenues such as 'epidrugs' and finally emphasize on the importance of targeted drug delivery systems for alleviating microglia-mediated neurotoxicity.

Topics: Animals; Drug Delivery Systems; Forecasting; Humans; Inflammation; Microglia; Nervous System Diseases; Plant Preparations; Reactive Oxygen Species; Signal Transduction; Tretinoin

Topics: Acetylation; Adult; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Child; China; Chromatin; Drug Evaluation; Drug Resistance, Neoplasm; Enzyme Inhibitors; Gastrointestinal Diseases; Histone Deacetylase Inhibitors; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Melarsoprol; Neoplasm Proteins; Neoplasms; Nervous System Diseases; Oxides; Phenylbutyrates; Protein Processing, Post-Translational; Salvage Therapy; Tretinoin

Acute promyelocytic leukemia (APL) is a rare but particularly malignant form of acute leukemia that is characterized by a rapid progression to fatal hemorrhage. Survival rates of patients with APL have increased with the introduction of all-trans retinoic acid (ATRA), but early deaths caused by hemorrhage still persist.. A man with undiagnosed APL presenting with focal neurologic findings and deteriorating altered mental status caused by an intracranial hemorrhage is discussed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important to consider APL when diagnosing etiologies for intracranial hemorrhage. In addition to standard care, early administration of ATRA is recommended upon clinical suspicion of the disease.

Topics: Blood Platelets; Consciousness; Emergency Service, Hospital; Factor VIII; Fibrinogen; Humans; Intracranial Hemorrhages; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Nervous System Diseases; Thrombocytopenia; Tomography, X-Ray Computed; Tretinoin

Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyurea) as listed by European Centre for the Validation of Alternative Methods (ECVAM) and examined endpoints of cell viability and neuronal protein marker expression specific to the central nervous system, to identify developmental neurotoxins. Following induction of neuronal differentiation, valproic acid had the most significant effect on neurogenesis, in terms of reduced viability and decreased neuronal markers. Lithium had least effect on viability and did not significantly alter the expression of neuronal markers. Hydroxyurea significantly reduced cell viability but did not affect neuronal protein marker expression. Acrylamide reduced neurosphere viability but did not affect neuronal protein marker expression. Overall, this NT2/D1-based neurosphere model of neurogenesis, may provide the basis for a model of developmental neurotoxicity in vitro.

Topics: Acrylamides; Blotting, Western; Cell Differentiation; Cell Line, Tumor; Cell Survival; Densitometry; Gene Expression; Humans; Hydroxyurea; Image Processing, Computer-Assisted; Immunohistochemistry; Lithium Chloride; Microscopy, Confocal; Models, Neurological; Nervous System Diseases; Neurons; Reverse Transcriptase Polymerase Chain Reaction; Teratogens; Tretinoin; Valproic Acid

Topics: Adult; Female; Humans; Leukemia, Promyelocytic, Acute; Nervous System Diseases; Tretinoin