• 1
    Marini C, Baldassarre M, Russo T, et al. Burden of first-ever ischemic stroke in the oldest old: evidence from a population-based study. Neurology. 2004; 62: 7781.
  • 2
    Kaste M, Fogelholm R, Rissanen A. Economic burden of stroke and the evaluation of new therapies. Public Health. 1998; 112: 10312.
  • 3
    Pohjasvaara T, Erkinjuntti T, Vataja R, et al. Dementia three months after stroke. Baseline frequency and effect of different definitions of dementia in the Helsinki Stroke Aging Memory Study (SAM) cohort. Stroke. 1997; 28: 78592.
  • 4
    Sachdev PS, Brodaty H, Valenzuela MJ, et al. Clinical determinants of dementia and mild cognitive impairment following ischaemic stroke: the Sydney Stroke Study. Dement Geriatr Cogn Disord. 2006; 21: 27583.
  • 5
    Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006; 3: e442.
  • 6
    Sahota P, Savitz SI. Investigational therapies for ischemic stroke: neuroprotection and neurorecovery. Neurotherapeutics. 2011; 8: 43451.
  • 7
    O'Collins VE, Macleod MR, Donnan GA, et al. 1,026 experimental treatments in acute stroke. Ann Neurol. 2006; 59: 46777.
  • 8
    Ginsberg MD. Neuroprotection for ischemic stroke: past, present and future. Neuropharmacology. 2008; 55: 36389.
  • 9
    Heiss WD. The ischemic penumbra: correlates in imaging and implications for treatment of ischemic stroke. The Johann Jacob Wepfer award 2011. Cerebrovasc Dis. 2011; 32: 30720.
  • 10
    Lakhan SE, Kirchgessner A, Hofer M. Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med. 2009; 7: 97.
  • 11
    Kuroda S, Siesjo BK. Reperfusion damage following focal ischemia: pathophysiology and therapeutic windows. Clin Neurosci. 1997; 4: 199212.
  • 12
    Kahles T, Luedike P, Endres M, et al. NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke. Stroke. 2007; 38: 30006.
  • 13
    Maneen MJ, Cipolla MJ. Peroxynitrite diminishes myogenic tone in cerebral arteries: role of nitrotyrosine and F-actin. Am J Physiol Heart Circ Physiol. 2007; 292: H104250.
  • 14
    Skoog I, Korczyn AD, Guekht A. Neuroprotection in vascular dementia: a future path. J Neurol Sci. 2012; 322: 2326.
  • 15
    Ziegler D, Movsesyan L, Mankovsky B, et al. Treatment of symptomatic polyneuropathy with actovegin in type 2 diabetic patients. Diabetes Care. 2009; 32: 147984.
  • 16
    Herrmann WM, Bohn-Olszewsky WJ, Kuntz G. Actovegin infusion treatment in patients with primarily degenerative dementia of the Alzheimer type and multi-infarct dementia. Zeitschrift für Geriatrie. 1992; 5: 4655.
  • 17
    Kanowski S, Kinzler E, Lehmann E, et al. Confirmed clinical efficacy of Actovegin in elderly patients with organic brain syndrome. Pharmacopsychiatry. 1995; 28: 12533.
  • 18
    Dieckmann A, Kriebel M, Andriambeloson E, et al. Treatment with Actovegin(R) improves sensory nerve function and pathology in streptozotocin-diabetic rats via mechanisms involving inhibition of PARP activation. Exp Clin Endocrinol Diabetes. 2012; 120: 1328.
  • 19
    Elmlinger MW, Kriebel M, Ziegler D. Neuroprotective and anti-oxidative effects of the hemodialysate actovegin on primary rat neurons in vitro. Neuromolecular Med. 2011; 13: 26674.
  • 20
    Machicao F, Muresanu DF, Hundsberger H, et al. Pleiotropic neuroprotective and metabolic effects of Actovegin's mode of action. J Neurol Sci. 2012; 322: 2227.
  • 21
    Buchmayer F, Pleiner J, Elmlinger MW, et al. Actovegin(R): a biological drug for more than 5 decades. Wien Med Wochenschr. 2011; 161: 808.
  • 22
    Sun N, Hao JR, Li XY, et al. GluR6-FasL-Trx2 mediates denitrosylation and activation of procaspase-3 in cerebral ischemia/reperfusion in rats. Cell Death Dis. 2013; 4: e771.
  • 23
    Annapurna A, Ansari MA, Manjunath PM. Partial role of multiple pathways in infarct size limiting effect of quercetin and rutin against cerebral ischemia-reperfusion injury in rats. Eur Rev Med Pharmacol Sci. 2013; 17: 491500.
  • 24
    Pulsinelli WA, Buchan AM. The four-vessel occlusion rat model: method for complete occlusion of vertebral arteries and control of collateral circulation. Stroke. 1988; 19: 9134.
  • 25
    Pulsinelli WA, Brierley JB. A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke. 1979; 10: 26772.
  • 26
    Bin J, Wang Q, Zhuo YY, et al. Piperphentonamine (PPTA) attenuated cerebral ischemia-induced memory deficits via neuroprotection associated with anti-apoptotic activity. Metab Brain Dis. 2012; 27: 495505.
  • 27
    Grogaard B, Gerdin B, Arfors KE. Forebrain ischemia in the rat. Relation between duration of ischemia, use of adjunctive ganglionic blockade and long-term recovery. Stroke. 1986; 17: 10105.
  • 28
    Raz L, Zhang QG, Zhou CF, et al. Role of Rac1 GTPase in NADPH oxidase activation and cognitive impairment following cerebral ischemia in the rat. PLoS ONE. 2010; 5: e12606.
  • 29
    Yasuda Y, Shimoda T, Uno K, et al. Temporal and sequential changes of glial cells and cytokine expression during neuronal degeneration after transient global ischemia in rats. J Neuroinflammation. 2011; 8: 70.
  • 30
    Chu K, Yin B, Wang J, et al. Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus. J Neuroinflammation. 2012; 9: 69.
  • 31
    Globus MY, Wester P, Busto R, et al. Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats. Stroke. 1992; 23: 1595601.
  • 32
    Clark RE, Zola SM, Squire LR. Impaired recognition memory in rats after damage to the hippocampus. J Neurosci. 2000; 20: 885360.
  • 33
    Broadbent NJ, Squire LR, Clark RE. Spatial memory, recognition memory, and the hippocampus. Proc Natl Acad Sci USA. 2004; 101: 1451520.
  • 34
    Lavenex PB, Amaral DG, Lavenex P. Hippocampal lesion prevents spatial relational learning in adult macaque monkeys. J Neurosci. 2006; 26: 454658.
  • 35
    Bartsch T, Schonfeld R, Muller FJ, et al. Focal lesions of human hippocampal CA1 neurons in transient global amnesia impair place memory. Science. 2010; 328: 14125.
  • 36
    Hoyer S, Betz K. Elimination of the delayed postischemic energy deficit in cerebral cortex and hippocampus of aged rats with a dried, deproteinized blood extract (Actovegin). Arch Gerontol Geriatr. 1989; 9: 18192.
  • 37
    Wang X, Zaidi A, Pal R, et al. Genomic and biochemical approaches in the discovery of mechanisms for selective neuronal vulnerability to oxidative stress. BMC Neurosci. 2009; 10: 12.
  • 38
    Kuninaka T, Senga Y, Senga H, et al. Nature of enhanced mitochondrial oxidative metabolism by a calf blood extract. J Cell Physiol. 1991; 146: 14855.
  • 39
    Derev'yannykh EA, Bel'skaya GN, Knoll EA, et al. Experience in the use of Actovegin in the treatment of patients with cognitive disorders in the acute period of stroke. Neurosci Behav Physiol. 2008; 38: 8735.
  • 40
    Dias Fiuza FE, Valerio RC, Cypriano PE, et al. Sildenafil provides sustained neuroprotection in the absence of learning recovery following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats. Brain Res Bull. 2013; 90: 5865.