Gredal Hanne, Thomsen Barbara B, Boza-Serrano Antonio, Garosi Laurent, Rusbridge Clare, Anthony Daniel, Møller Arne, Finsen Bente, Deierborg Tomas, Lambertsen Kate L, Berendt Mette
aDepartment of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg bCentre of Functionally Integrative Neuroscience, Aarhus University, Aarhus cDepartment of Neurobiology Research, Institute of Molecular Medicine dBRIDGE (Brain Research - Inter-Disciplinary Guided Excellence), Department of Clinical Research, University of Southern Denmark eDepartment of Neurology, Odense University Hospital, Odense, Denmark fExperimental Neuroinflammation Laboratory, Department of Experimental Medical Science, BMC, Lund University, Lund, Sweden gDavies Veterinary Specialists, Hitchin hFitzpatrick Referrals, Surrey iDepartment of Pharmacology, University of Oxford, Oxford, UK *Shared senior authorship.
Neuroreport. 2017 Feb 8;28(3):134-140. doi: 10.1097/WNR.0000000000000728.
Inflammatory cytokines are potential modulators of infarct progression in acute ischaemic stroke, and are therefore possible targets for future treatment strategies. Cytokine studies in animal models of surgically induced stroke may, however, be influenced by the fact that the surgical intervention itself contributes towards the cytokine response. Community-dwelling domestic dogs suffer from spontaneous ischaemic stroke, and therefore, offer the opportunity to study the cytokine response in a noninvasive set-up. The aims of this study were to investigate cytokine concentrations in plasma and cerebrospinal fluid (CSF) in dogs with acute ischaemic stroke and to search for correlations between infarct volume and cytokine concentrations. Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic stroke. Infarct volumes were estimated on MRIs. Interleukin (IL)-2, IL-6, IL-8, IL-10 and tumour necrosis factor in the plasma, CSF and brain homogenates were measured using a canine-specific multiplex immunoassay. IL-6 was significantly increased in plasma (P=0.04) and CSF (P=0.04) in stroke dogs compared with healthy controls. The concentrations of other cytokines, such as tumour necrosis factor and IL-2, were unchanged. Plasma IL-8 levels correlated significantly with infarct volume (Spearman's r=0.8, P=0.013). The findings showed increased concentrations of IL-6 in the plasma and CSF of dogs with acute ischaemic stroke comparable to humans. We believe that dogs with spontaneous stroke offer a unique, noninvasive means of studying the inflammatory processes that accompany stroke while reducing confounds that are unavoidable in experimental models.
炎症细胞因子是急性缺血性卒中梗死进展的潜在调节因子,因此可能是未来治疗策略的靶点。然而,在手术诱导的卒中动物模型中进行的细胞因子研究可能会受到手术干预本身会对细胞因子反应产生影响这一事实的影响。家养宠物狗会患自发性缺血性卒中,因此提供了在非侵入性条件下研究细胞因子反应的机会。本研究的目的是调查急性缺血性卒中犬血浆和脑脊液(CSF)中的细胞因子浓度,并寻找梗死体积与细胞因子浓度之间的相关性。在自发性缺血性卒中发生后72小时内从犬只采集血液和脑脊液。通过磁共振成像(MRI)估计梗死体积。使用犬特异性多重免疫测定法测量血浆、脑脊液和脑匀浆中的白细胞介素(IL)-2、IL-6、IL-8、IL-10和肿瘤坏死因子。与健康对照相比,卒中犬血浆(P = 0.04)和脑脊液(P = 0.04)中的IL-6显著升高。其他细胞因子如肿瘤坏死因子和IL-2的浓度没有变化。血浆IL-8水平与梗死体积显著相关(Spearman相关系数r = 0.8,P = 0.013)。研究结果表明,急性缺血性卒中犬血浆和脑脊液中IL-6浓度升高,与人类情况相似。我们认为,自发性卒中犬提供了一种独特的、非侵入性的手段来研究伴随卒中的炎症过程,并减少实验模型中不可避免的混杂因素。