TiHo Bibliothek elib - Tierärztliche Hochschule Hannover

More documents

Recommendations

Info

Untersuchung des Chemokins MIP-3 β/CCL19 Abstract Background: Chemokines are important factors in the mechanism of cell migration and pathogenesis of central nervous system (CNS) inflammatory reactions. MIP- 3β/CCL19 is one chemokine that may play a major role in this context. Objective: The aim of this study was to prove the hypothesis that MIP-3β/CCL19 is involved in the pathogenesis of mononuclear cell migration into the subarachnoid space of dogs with inflammatory and non-inflammatory CNS diseases such as steroid-responsive meningitis-arteritis (SRMA) and intervertebral disc disease (IVDD) and may serve as a valuable biomarker for the progression of the diseases. Material and methods: This retrospective study analyzed a total of 141 dogs. Experiments were performed on cerebrospinal fluid (CSF) and peripheral blood (PB) samples of dogs affected with SRMA during the acute phase (n = 25) as well as during treatment (n = 26). Dogs with SRMA were compared to dogs with presumed meningoencephalomyelitis of unknown origin (MUO) receiving no therapy (n = 16) and with patients receiving prednisolone therapy (n= 11). A control group with normal cell count consisted of dogs with Idiopathic Epilepsy (IE) (n= 21) and of healthy dogs (n= 6). Additionally, dogs with IVDD of varying severity (n= 36) were analyzed. Concentration of MIP-3β/CCL19 in the CSF and serum were determined by a sandwich ELISA. Migration assays were performed on seven selected CSF samples using a disposable 96-well chemotaxis chamber (untreated SRMA n = 3 ; untreated MUO n = 2 ; IVDD n = 2). Results: MIP-3β/CCL19 was detectable in CSF samples of all dogs. Dogs with untreated SRMA/MUO displayed pronounced MIP-3β/CCL19 elevations compared to the control group and patients receiving glucocorticosteroid treatment. CSF cell count of untreated SRMA/MUO patients was significantly positively correlated with the MIP-3β/CCL19 CSF concentration. IVDD patients also had elevated CSF MIP-3β/CCL19 concentration compared to controls, but values were considerably lower than in inflammatory CNS diseases. Selected CSF samples including inflammatory and non-inflammatory neurologic diseases displayed 32
Untersuchung des Chemokins MIP-3 β/CCL19 chemotactic activity for mononuclear cells in the migration assay, proving that the measured CSF protein is available in the active form. Conclusions: The hypothesis was confirmed that MIP-3β/CCL19 is involved in the pathogenesis of SRMA/MUO, possibly perpetuating an autoimmune reaction. The marked chemotactic activity for mononuclear cells leads to the assumption that this chemokine could be associated with the migration of mononuclear cells into the subarachnoid space of dogs. The elevation of CSF MIP-3β/CCL19 in IVDD suggests that it also plays a role in the secondary wave in spinal cord injuries (SCI). CSF MIP- 3β/CCL19 concentration may serve as a prognostic indicator in SCI, be a precious biomarker for developing new treatment schemes and for verifying the success of treatment. 1. Introduction In several neurologic diseases a pleocytosis is often detected in the cerebrospinal fluid (CSF). Lymphocytes and plasma cells have been shown to prevail in the cell count in viral infections (Wamsley and Alleman 2004), chronic steroid responsive meningitis-arteritis (SRMA) (Tipold and Jaggy 1994), granulomatous meningoencephalomyelitis (GME) and in necrotizing encephalitides (NE) (Wamsley and Alleman 2004; Talarico and Schatzberg 2010). A neutrophilic pleocytosis is characteristic for bacterial infections and the acute stage of SRMA (Tipold and Jaggy 1994). A mixed cell population can be seen in protozoal diseases, chronic bacterial infections, necrotic lesions, and in GME (Wamsley and Alleman 2004). In addition to inflammatory lesions, mild mixed cell pleocytosis can also be seen with situations such as acute intervertebral disc herniation that results in central nervous system (CNS) myelomalacia or infarction (Chrisman 1992). Chemokines are important factors in the mechanism of cell migration and thus play a relevant role in the pathogenesis of inflammation in the CNS (Dogan and Karpus 2004). They upregulate surface molecules on circulating inflammatory cells in the periphery which enable them to more efficiently adhere to the endothelial cells of the blood-brain barrier (BBB) and react to the CNS chemokine gradients (Constantin 33
Page 1 and 2: Tierärztliche Hochschule Hannover
Page 3 and 4: Meinen Eltern
Page 5 and 6: Inhaltsverzeichnis INHALTSVERZEICHN
Page 7 and 8: Einleitung Kapitel 1 Einleitung Ent
Page 9 and 10: Literaturübersicht Kapitel 2 Liter
Page 11 and 12: Literaturübersicht erhöhtem Gesam
Page 13 and 14: Literaturübersicht der Entwicklung
Page 15 and 16: Literaturübersicht Häufig wird ei
Page 17 and 18: Literaturübersicht besitzen Patien
Page 19 and 20: Literaturübersicht Sie können Obe
Page 21 and 22: Material und Methoden Kapitel 3 Mat
Page 23 and 24: Material und Methoden - Tischzentri
Page 25 and 26: Material und Methoden 3.3. Methode
Page 27 and 28: Material und Methoden Abb. 1: Prinz
Page 29 and 30: Material und Methoden wurde jeweils
Page 31: Untersuchung des Chemokins MIP-3 β
Page 35 and 36: Untersuchung des Chemokins MIP-3 β
Page 59 and 60: Falldarstellung Kapitel 5 Falldarst
Page 61 and 62: Falldarstellung the central nervous
Page 63 and 64: Falldarstellung set at a rate of 49
Page 65 and 66: Falldarstellung Fig. 3 Fig. 1, Fig.
Page 67 and 68: Falldarstellung present, the evalua
Page 69 and 70: Falldarstellung bacterial growth (D
Page 71 and 72: Falldarstellung high risk of brain
Page 73 and 74: Falldarstellung However, at the ini
Page 75 and 76: Falldarstellung Adjunctive glucocor
Page 77 and 78: Falldarstellung Versed®; Roche Eto
Page 79 and 80: Falldarstellung in: A. LAJTHA, A. G
Page 81 and 82: Falldarstellung KING, N. (2010): Br
Page 83 and 84:
Falldarstellung PLATT, S.R., u. N.
Page 85 and 86:
Falldarstellung VITE, C.H. (2005):
Page 87 and 88:
Übergreifende Diskussion Organismu
Page 89 and 90:
Übergreifende Diskussion Neutrophi
Page 91 and 92:
Übergreifende Diskussion Rückenma
Page 93 and 94:
Zusammenfassung Kapitel 7 Zusammenf
Page 95 and 96:
Zusammenfassung In dieser Studie ko
Page 97 and 98:
Summary Increased intrathecal chemo
Page 99 and 100:
Abkürzungsverzeichnis Kapitel 9 Ab
Page 101 and 102:
Abkürzungsverzeichnis SRMA Std. T
Page 103 and 104:
Literaturverzeichnis BAUMGÄRTNER,
Page 105 and 106:
Literaturverzeichnis CHERUBINI, G.
Page 107 and 108:
Literaturverzeichnis DE LAHUNTA, A.
Page 109 and 110:
Literaturverzeichnis FUCHS, C., S.
Page 111 and 112:
Literaturverzeichnis JEFFERY, N.D.
Page 113 and 114:
Literaturverzeichnis KLOPP, L.S., J
Page 115 and 116:
Literaturverzeichnis MADDISON, J.E.
Page 117 and 118:
Literaturverzeichnis PASHENKOV, M.,
Page 119 and 120:
Literaturverzeichnis SCHATZBERG, S.
Page 121 and 122:
Literaturverzeichnis SERAFINI, B.,
Page 123 and 124:
Literaturverzeichnis TALARICO, L.R.
Page 125 and 126:
Literaturverzeichnis UCHIDA, K., T.
Page 127 and 128:
Anhang Kapitel 12 Anhang Materialvo
Page 129 and 130:
Anhang E: TMB Substrat: Das benöt
Page 131 and 132:
Anhang 9. Die Flüssigkeit, welche
Page 133 and 134:
Anhang 4. Anschließend wird das ve
Page 135 and 136:
Anhang 1. Anzahl der Hunde, Diagnos
Page 137 and 138:
Anhang 2. Anzahl der Hunde, Diagnos
Page 139 and 140:
Anhang Lfd. Nr. Diagnose Grad Vorst
Page 141 and 142:
Danksagung Kapitel 13 Danksagung Me
show all

TiHo Bibliothek elib - Tierärztliche Hochschule Hannover

Create successful ePaper yourself

Delete template?

Save as template?