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London, United Kingdom 2013 467 Experimental studies Dexamethasone reduces brain cell apoptosis and inhibits inflammatory response in rats with intracerebral hemorrhage J.T. Yang1, M.H. Lee2, W.C. Cheng3, M.H.C. Lin4, I.N Lee5, C.H Kuo6 Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi, Pu Tz City, TAI-WAN1, Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi, Pu Tz City, Chia- Yi, TAIWAN2, Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi, Pu Tz City, Chia-Yi, TAIWAN3, Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi, Pu Tz City, Chia-Yi, TAIWAN4, Department of Neurosurgery, Chang Gung Memorial Hospital, Chia- Yi, Pu Tz City, Chia-Yi, TAIWAN5, Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi, Pu Tz City, Chia-Yi, TAIWAN6 Although the risk factors for stroke are well known from epidemiological studies, diagnosis and management of strokes remains difficult. Spontaneous intracerebral hemorrhage (ICH) accounts for 10 to 15% of all strokes and is associated with high rates of mortality and morbidity. Dexametha-sone (DEX) is a synthetic glucocorticoid used clinically to reduce edema formation in patients with spinal cord injury and brain tumors. However, its utility in stroke management has produced con-flicting results. In this study, we sought to elucidate the effects of DEX treatment on apoptosis and inflammation following ICH in rats. ICH was induced in rats by intracranial stereotactic injection of collagenase into the caudate nucleus. A high dose of DEX (15 mg/kg) was administered immediate-ly following ICH induction and then again 4 days later. The inflammatory and apoptotic responses in the rat brains were evaluated using hematoxylin-eosin (H & E), Nissl and neurofilament-H stain-ing. Levels of apoptosis-related proteins, such as B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase-3 and P53 were analyzed by western blotting. Our results show rats without ICH receiving DEX treatment had 4-fold higher expression of Bcl-2 than sham-operated rats, while there was no significant change in the level of Bax between these 2 groups. ICH causes an increase in Bax, cleaved caspase-3 and P53 proteins from 4 h to 7 days following ICH induction. Compared to the ICH-only rats, the ICH/DEX rats significantly increased the Bcl-2:Bax ratio and lowered the expression of cleaved caspase-3 at 12 h and 5 days and P53 at 1 day. In the meantime, the ICH rats were accompanied by activation of the inflammatory response and DEX treatment can modulate the expression of a variety of cell types including neutrophils, macrophages, oligodendroglial cells and neurons then decreased ICH-induced apoptosis. Together, these data indicate that a regimen of time-ly DEX treatment may have beneficial effects in the management of hemorrhagic stroke. Poster Session Red Cerebrovasc Dis 2013; 35 (suppl 3)1-854 535 466 Experimental studies HDL-based therapy reduces the hemorrhagic complications associated with tissue plasmino-gen activator treatment in experimental stroke L.B. LAPERGUE1, B.Q.D. DANG2, J.P.D. DESILLES3, G.O. ORTIZ4, S.D. DELBOSC5, S.L. LOYAU6, L.L. LOUEDEC7, P.O.C. COURAUD8, M.M. MAZIGHI9, J.B.M. MICHEL10, O.M. MEILHAC11, P.A. AMARENCO12 INSERM U-698 and Department of Neurology and Stroke Centre, Bichat University Hospi-tal,, PARIS, FRANCE1, INSERM U-698 Bichat University Hospital,, PARIS, FRANCE2, INSERM U-698, Bichat University Hospital,, PARIS, FRANCE3, INSERM U-698, Bichat University Hospi-tal,, PARIS, FRANCE4, INSERM U-698, Bichat University Hospital,, PARIS, FRANCE5, INSERM U-698, Bichat University Hospital,, PARIS, FRANCE6, INSERM U-698, Bichat University Hos-pital,, PARIS, FRANCE7, Institut Cochin, université Paris-Descartes,, PARIS, FRANCE8, Institut Cochin, université Paris-Descartes, Paris,, PARIS, FRANCE9,INSERM U-698, Bichat University Hospital,, PARIS, FRANCE10, INSERM U-698, Bichat University Hospital,, PARIS, FRANCE11, INSERM U-698 and Department of Neurology and Stroke Centre, Bichat University Hospital,, PARIS, FRANCE12 Background We have previously reported that intravenous injection of high density lipoproteins (HDLs) was neuroprotective in an embolic stroke model. We hypothesized that HDL vasculoprotective actions on the blood-brain barrier (BBB) may decrease hemorrhagic transformation (HT)-associated with tPA administration in acute stroke. Methods and Results We used tPA alone or in combination with HDLs in vivo in two models of focal middle cerebral ar-tery occlusion (embolic, eMCAO and 4 hours monofilament fMCAO), and in vitro on a model of BBB. Sprague-Dawley rats were submitted to a MCAO, n=12/group. The rats were then randomly injected with tPA (10 mg/kg) or saline with or without human plasma purified-HDL (10 mg/kg). The therapeutic effects of HDL and BBB integrity were assessed blindly 24 hours later. The integrity of the BBB was also tested using an in vitro model of human cerebral endothelial cells under oxy-gen- glucose deprivation (OGD). tPA-treated groups had significantly higher mortality and rate of HT at 24 hours in both MCAO models. Co-treatment with HDL significantly reduced stroke-induced mortality versus tPA alone (by 42% in fMCAO, P=0.009; by 73% in eMCAO, P=0.05) and tPA-induced intracerebral parenchy-mal hematoma (by 92% in fMCAo; by 100% in eMCAo, P<0.0001). This was consistent with an improved BBB integrity. In vitro, HDLs decreased OGD-induced BBB permeability (P<0.05) and VE-Cadherin disorganization. Conclusions HDL injection decreased tPA-induced hemorrhagic transformation in rat models of MCAO. Both in vivo and in vitro results support the vasculoprotective action of HDLs on BBB under ischemic con-ditions.


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