Inflammation as therapeutic objective in stroke.
Ischemic stroke is the most frequent cause of persistent neurologic disability in modern Western societies. Albeit it is still not clear whether inflammation is merely an epiphenomenon or rather has a disease-promoting function, accumulating evidence implicates inflammation in many forms of acute neurodegenerative disorders including ischemia. The immune cell influx during a neuropathological event is thought to be elicited by glial cells, especially microglia. This article reviews the cellular and molecular pathways involved in stroke-induced inflammatory response in the CNS. We focused on how CNS innate immune cells including microglia and macrophages play integral roles in receiving and propagating inflammatory signals, and how activated microglia secrete a wide range of factors. We present the relevance of the expression of adhesion molecules after ischemia including selectin, immunoglobulin superfamily, integrins, and the role of inflammatory mediators such as cytokines, chemokines and matrix metalloproteinases. Further, we explore the role of transcription factors in inflammation, and the function of immunomodulation and innate and adaptive immunity in brain ischemia, focusing on immunosupression therapies for acute stroke. Although several approaches for anti-inflammatory treatment have proven effective in animal models, clinical trials of immune system modulation therapy after stroke have not yet proved successful. There is still much to be done in order to translate interesting findings into therapies, but undoubtedly studying the cellular and molecular pathways may not only improve our understanding of inflammatory mechanism but also serve as a basis for designing effective therapies.
Jordán
Joaquín
J
Grupo de Neurofarmacologia, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha. Centro Regional de Investigaciones Biomédicas, Avda Almansa, 14, 02006-Albacete, Spain. Joaquin.jordan@uclm.es
Segura
Tomás
T
Brea
David
D
Galindo
Maria F
MF
Castillo
José
J
D002545:Brain Ischemia / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy* / Q000276:immunology*
D007155:Immunologic Factors; D018836:Inflammation Mediators