Niaspan treatment induces neuroprotection after stroke (original) (raw)
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Journal of the Neurological Sciences, 2011
Introduction-Niaspan, an extended-release formulation of Niacin (vitamin B3), has been widely used to increase high density lipoprotein (HDL) cholesterol and to prevent cardiovascular diseases and stroke. We have previously demonstrated that Niaspan (40mg/kg) administered at 2 hours after stroke induces neuroprotection, while low dose Niaspan (20mg/kg) does not reduce infarct volume. Tissue plasminogen activator (tPA) is an effective therapy for acute stroke, but its use remains limited by narrow therapeutic window. We have previously demonstrated that intravenous administration of tPA 4 hours after stroke in rats does not reduce infarct volume. In this study, we tested whether combination treatment with low-dose Niaspan (20mg/kg) and tPA administered 4 hours after embolic stroke in a rat model reduces infarct volume and provides neuroprotection.
Niaspan increases angiogenesis and improves functional recovery after stroke
Annals of Neurology, 2007
Objective: High-density lipoprotein (HDL) is implicated in the modulation of angiogenesis. In this study, we investigated whether the Niacin-mediated increase of HDL regulates angiogenesis and thereby improves functional outcome after stroke. Methods: Adult male rats were subjected to middle cerebral artery occlusion and were treated with or without different doses (40 and 80mg/kg) of Niaspan, starting 24 hours after middle cerebral artery occlusion and daily for 14 days. Neurological functional tests were performed, and serum HDL level was measured. Angiogenesis and angiogenic factor expression were measured by immunohistochemistry, corneal neovascularization and capillary tube formation assay, and Western blot, respectively. Results: Niaspan significantly increased HDL level, promoted angiogenesis in the ischemic brain, and improved functional outcome after stroke. Niaspan also significantly increased corneal neovascularization compared with nontreatment control. Mechanisms underlying the Niaspan-induced vascular remodeling were investigated. Niaspan increased the expression of vascular endothelial growth factor and angiopoietin-1 (Ang1), and phosphorylation of Akt, endothelial nitric oxide synthase (NOS), and Tie2 in the ischemic brain. Niacin upregulated Ang1 expression in cultured brain endothelial cells and increased vascular endothelial growth factor, Ang1, and endothelial NOS expression in cultured astrocytes, and dose-dependently increased capillary tube formation compared with nontreatment control. Inhibition of NOS partially decreased Niacin-induced capillary tube formation. Inhibition of phosphoinositide 3-kinase or knockdown of Tie2 substantially and significantly decreased Niacininduced capillary tube formation. Interpretation: Niacin increases HDL and promotes angiogenesis, which may contribute to improvement of functional outcome after stroke. The Ang1/Tie2, phosphoinositide 3-kinase/Akt, and endothelial NOS pathways appear to mediate Niacin-induced angiogenesis.
Niaspan enhances vascular remodeling after stroke in type 1 diabetic rats
Experimental Neurology, 2011
We investigated the changes and the molecular mechanisms of cerebral vascular damage and tested the therapeutic effects of Niaspan in type-1 streptozotocin induced diabetic (T1DM) rats after stroke. T1DM-rats were subjected to transient middle cerebral artery occlusion (MCAo) and treated without or with Niaspan. Non-streptozotocin rats (WT) were also subjected to MCAo. Functional outcome, blood-brain-barrier (BBB) leakage, brain hemorrhage, immunostaining, and rat brain microvascular endothelial cell (RBEC) culture were performed. Compared to WT-MCAo-rats, T1DM-MCAo-rats did not show an increase lesion volume, but exhibited significantly increased brain hemorrhage, BBB leakage and vascular damage as well as decreased functional outcome after stroke. Niaspan treatment of stroke in T1DM-MCAo-rats significantly attenuated BBB damage, promoted vascular remodeling and improved functional outcome after stroke. T1DM-MCAo-rats exhibited significantly increased Angiopoietin 2 (Ang2) expression, but decreased Ang1 expression in the ischemic brain compared to WT-MCAo-rats. Niaspan treatment attenuated Ang2, but increased Ang1 expression in the ischemic brain in T1DM-MCAo-rats. In vitro data show that the capillary-like tube formation in the WT-RBECs marginally increased compared to T1DM-RBEC. Niaspan and Ang1 treatment significantly increased tube formation compared to non-treatment control. Inhibition of Ang1 attenuated Niacin-induced tube formation in T1DM-RBECs. Niaspan treatment of stroke in T1DM-rats promotes vascular remodeling and improves functional outcome. The Ang1/Ang2 pathway may contribute to Niaspan induced brain plasticity. Niaspan warrants further investigation as a therapeutic agent for the treatment of stroke in diabetics.
Neuroscience, 2011
Objective-High-mobility group box 1 (HMGB1), an active receptor for advanced glycation endproducts (RAGE), functions as a potent proinflammatory cytokine-like factor that contributes to the pathogenesis of vasculature. Diabetes mellitus (DM) is associated with accelerated development of both microvascular and macrovascular disease and increases the risk of ischemic stroke. Using a model of streptozotocin-induced type-1 diabetes (T1DM) in rats, we investigated the changes in HMGB and RAGE and tested the effects of Niaspan, a slow release form of niacin, on the expression of pro-inflammatory proteins in rats after stroke.
Ischemic stroke and neuroprotection
Annals of Medical and Health Sciences Research, 2012
It is the third leading cause of death in Western countries. [2] In Africa it accounts for 4-9% of deaths and between 6.5% and 41% of neurological admissions in hospital based studies. [3] Findings from South West Nigeria show that the incidence of stroke rises with age reaching a peak in the 8 th decade in males and 7 th decade in females. [4] Stroke is classified as being either hemorrhagic or ischemic in nature depending on the underlying pathological process responsible. Several studies have documented that the ischemic subtype accounts for the greater number of stroke cases. [5-8] An ischemic stroke occurs when a cerebral vessel occludes, obstructing blood flow to a portion of the brain. The only currently approved medical stroke therapy, tissue plasminogen activator (tPA), is a thrombolytic that targets the thrombus within the blood vessel. Neuroprotective agents, another approach to stroke treatment, have generated as much interest as thrombolytic therapies. Materials and Methods An extensive search of all materials related to the topic was made using library sources including Pubmed and Medline searches. Current research findings were also included.
Chinese Medicine Neuroaid Efficacy on Stroke Recovery
Stroke, 2013
Background and Purpose— Previous clinical studies suggested benefit for poststroke recovery when MLC601 was administered between 2 weeks and 6 months of stroke onset. The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study tested the hypothesis that MLC601 is superior to placebo in acute, moderately severe ischemic stroke within a 72-hour time window. Methods— This multicenter, double-blind, placebo-controlled trial randomized 1100 patients with a National Institutes of Health Stroke Scale score 6 to 14, within 72 hours of onset, to trial medications for 3 months. The primary outcome was a shift in the modified Rankin Scale. Secondary outcomes were modified Rankin Scale dichotomy, National Institutes of Health Stroke Scale improvement, difference in National Institutes of Health Stroke Scale total and motor scores, Barthel index, and mini-mental state examination. Planned subgroup analyses were performed according to age, sex, time to first dose, baseline National I...
2013
Abstract: The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with p...
Neuroprotection in Acute Ischemic Stroke: A Battle Against the Biology of Nature
Frontiers in Neurology
Stroke is the second most common cause of global death following coronary artery disease. Time is crucial in managing stroke to reduce the rapidly progressing insult of the ischemic penumbra and the serious neurologic deficits that might follow it. Strokes are mainly either hemorrhagic or ischemic, with ischemic being the most common of all types of strokes. Thrombolytic therapy with recombinant tissue plasminogen activator and endovascular thrombectomy are the main types of management of acute ischemic stroke (AIS). In addition, there is a vital need for neuroprotection in the setting of AIS. Neuroprotective agents are important to investigate as they may reduce mortality, lessen disability, and improve quality of life after AIS. In our review, we will discuss the main types of management and the different modalities of neuroprotection, their mechanisms of action, and evidence of their effectiveness after ischemic stroke.