title: Omega-3 polyunsaturated fatty acids ameliorate neuroinflammation and mitigate ischemic stroke damage through interactions with astrocytes and microglia.
abstract: Omega-3 polyunsaturated fatty acids (PUFA n3) provide neuroprotection due to their anti-inflammatory and anti-apoptotic properties as well as their regulatory function on growth factors and neuronal plasticity. These qualities enable PUFA n3 to ameliorate stroke outcome and limit neuronal damage. Young adult male rats received transient middle cerebral artery occlusion (tMCAO). PUFA n3 were intravenously administered into the jugular vein immediately after stroke and 12h later. We analyzed stroke volume and behavioral performance as well as the regulation of functionally-relevant genes in the penumbra. The extent of ischemic damage was reduced and behavioral performance improved subject to applied PUFA n3. Expression of Tau and growth-associated protein-43 genes were likewise restored. Ischemia-induced increase of cytokine mRNA levels was abated by PUFA n3. Using an in vitro approach, we demonstrate that cultured astroglial and microglia directly respond to PUFA n3 administration by preventing ischemia-induced increase of cyclooxygenase 2, hypoxia-inducible factor 1alpha, inducible nitric oxide synthase, and interleukin 1beta. Cultured cortical neurons also appeared as direct targets, since PUFA n3 shifted the Bcl-2-like protein 4 (Bax)/B-cell lymphoma 2 (Bcl 2) ratio towards an anti-apoptotic constellation. Thus, PUFA n3 reveal a high neuroprotective and anti-inflammatory potential in an acute ischemic stroke model by targeting astroglial and microglial function as well as improving neuronal survival strategies. Our findings signify the potential clinical feasibility of PUFA n3 therapeutic treatment in stroke and other acute neurological diseases.
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Adib
authors.initials: A
authors.lastname: Zendedel
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Pardes
authors.initials: P
authors.lastname: Habib
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Jon
authors.initials: J
authors.lastname: Dang
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Leoni
authors.initials: L
authors.lastname: Lammerding
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Germany. Electronic address: cbeyer@ukaachen.de.
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Slowik
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D020520:Brain Infarction / Q000188:drug therapy* / Q000209:etiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology; D005227:Fatty Acids / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009069:Movement Disorders / Q000209:etiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012678:Sensation Disorders / Q000188:drug therapy / Q000209:etiology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D019922:GAP-43 Protein
keywords: Astroglia; Cerebral cortex; Hypoxia; Microglia; Neuroinflammation; Neuron; PUFA n3; Rat