Cerebrovascular Disorders and Stroke Recovery

Our group has strong clinical and experimental expertise in translational research from stroke prevention and acute treatment to rehabilitation. The goal is to develop better tools for stroke acute treatment (e.g. thrombolysis, mechanical thrombectomy, surgical treatment, intensive care treatment) and to understand the factors that modulate neuronal plasticity and recovery of function after stroke, which information is needed in development of safe and effective interventions to help stroke patients with disabilities.

Stroke acute treatment is being actively investigated at the NeuroCenter – Neurology, Kuopio University Hospital (KUH). Our special strength is a strong continuum between basic and clinical research that enables translation of basic research innovations to clinical practices. Translational research group has excellent facilities at the National Animal Centre at Kuopio University, with immediate access to mice and rats and to a small animal imaging. A number of behavioral tests sensitive to brain damage and treatment effects are available.

The necessary equipments for classical anatomic approaches from electron microscopy to stereological counting methods are available. The current focus is on cell-based therapies, intensive rehabilitative training and restorative pharmacotherapy. Stroke rehabilitation research has also a continuum to clinical neurorehabilitation through strong collaboration with the KUH and The Finnish Brain Research and Rehabilitation Center Neuron.

 

STROKE

TRANSLATIONAL RESEARCH

NEUROLOGICAL REHABILATATION

  • Acute phase treatments (thrombolysis, mechanical thrombectomy, decompressive surgery, intensive care treatment, cost-effectiveness)
  • Mechanisms and imaging of cardiogenic embolism
  • Secondary prevention
  • Rehabilitation
  • Experimental stroke models
  • Predictive behavioral outcome measures
  • Histology
  • Small animal imaging (SPECT, MRI, fMRI)
  • Effectiveness and cost-effectiveness of rehabilitation
  • Mechanisms of recovery
  • New methods

Selected Publications

Effect of Middle Cerebral Artery Territory Ischemic Stroke on QT Interval. Simula S, Muuronen AT, Taina M, Jäkälä P, Sipola P, Vanninen R, Hedman M. J Stroke Cerebrovasc Dis. 2014 Apr;23(4):717-23.

Human bone marrow mesenchymal cells produce efficient localization in the brain and enhanced angiogenesis after intra-arterial delivery in rats with cerebral ischemia, but this is not translated to behavioral recovery. Mitkari B, Nitzsche F, Kerkelä E, Kuptsova K, Huttunen J, Nystedt J, Korhonen M, Jolkkonen J. Behav Brain Res 259: 50-9, 2014.

Determinants of left atrial appendage volume in stroke patients without chronic atrial fibrillation. Taina M, Sipola P, Muuronen A, Hedman M, Mustonen P, Kantanen AM, Jäkälä P, Vanninen R. PLoS One. 2014 Mar 4;9(3).

Left atrial appendage volume increased in more than half of patients with cryptogenic stroke. Taina M, Vanninen R, Hedman M, Jäkälä P, Kärkkäinen S, Tapiola T, Sipola P. PLoS One. 2013 Nov 4;8(11).

Edoxaban versus warfarin in patients with atrial fibrillation. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. N Engl J Med. 2013 Nov 28;369(22):2093-104.

Constraint-induced movement therapy overcomes the intrinsic axonal growth inhibitory signals in stroke rats. Zhao S, Zhao M, Xiao T, Jolkkonen J, Zhao Cs. Stroke 44:1698-705, 2013.

Stromal cell-derived factor-1 and its receptor CXCR4 in adult neurogenesis after cerebral ischemia. Cui L, Qu H, Xiao T, Zhao M, Jolkkonen J, Zhao C. Restor Neurol Neurosci 31:239-51, 2013.

Restorative therapies to enhance sensorimotor recovery following cerebral ischemia. Ortega FJ, Jolkkonen J. Acta Neurobiol Exp (Wars) 73:66-78, 2013.

Cell-Based Therapies in Stroke. (Eds. Jukka Jolkkonen, Piotr Walczak). Springer. 2013.

Nonselective calcium channel blocker bepridil decreases secondary thalamus pathology in mice after photothrombotic cortical lesion. Lipsanen A, Flunkert S, Kuptsova K, Hiltunen M, Windisch M, Hutter-Paier B, Jolkkonen J. PLoS ONE 8(3): e60235, 2013.

Lack of secondary β-amyloid and calcium pathology in the thalamus after focal cerebral ischemia in nonhuman primates. Lipsanen A, Kalesnykas G, Pro-Sistiaga P, Hiltunen M, Vanninen R, Bernaudin M, Touzani O, Jolkkonen J. Exp Neurol 248C:224-227, 2013.

Intra-arterial infusion of human bone marrow-derived mesenchymal stem cells result in transient localization in the brain after cerebral ischemia in rats. Mitkari B, Kerkelä E, Nystedt J, Korhonen M, Huhtala T, Jolkkonen J. Exp Neurol 239:158-162, 2013.

Increased neurogenesis contributes to the promoted behavioral recovery by constraint-induced movement therapy after stroke in adult rats. Zhao S, Zhao Y, Xiao T, Zhao M, Jolkkonen J, Zhao C. CNS Neurosci Ther 19:194-196, 2013.

Microglia is an active player in how glibenclamide improves stroke outcome. Ortega FJ, Jolkkonen J, Rodríguez MJ. J Cereb Blood Flow Metab 33:1138-9, 2013.

Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia. Ortega FJ, Jolkkonen J, Mahy N, Rodríguez MJ. J Cereb Blood Flow Metab 33:356-364, 2013.

Intravascular cell therapy in stroke patients: where the cells go and what they do. Korhonen M, Jolkkonen J. Regen Med 8: 93-95, 2013.

Gait impairment in a rat model of focal cerebral ischemia. Parkkinen S, Ortega FJ, Kuptsova K, Huttunen J, Tarkka I, Jolkkonen J. Stroke Res Treat, ID 410972, 2013.

Computed tomography and echocardiography together reveal more high-risk findings than echocardiography alone in the diagnostics of stroke etiology. Sipola P, Hedman M, Onatsu J, Turpeinen A, Halinen M, Jäkälä P, Vanninen R. Cerebrovasc Dis. 2013;35(6):521-30.

Toward a more effective intravascular cell therapy in stroke. Mitkari B, Kerkelä E, Nystedt J, Korhonen M, Huhtala T, Jolkkonen J. In: Advances in the Treatment of Ischemic Stroke, ed. Balestrino M. Intech, 141-160, 2012.

Bepridil decreases Aβ and calcium levels in the thalamus after middle cerebral artery occlusion in rats. Sarajärvi T, Lipsanen A, Mäkinen P, Peräniemi S, Soininen H, Haapasalo AK, Jolkkonen J, Hiltunen M. J Cell Mol Med 16:2754-67, 2012.

Letter by Hiltunen and Jolkkonen regarding article, "Secondary neurodegeneration in remote regions after focal cerebral infarction: a new target for stroke management?". Hiltunen M, Jolkkonen J. Stroke 43:e96, 2012.

Vorapaxar in the secondary prevention of atherothrombotic events. Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, Fox KA, Lipka LJ, Liu X, Nicolau JC, Ophuis AJ, Paolasso E, Scirica BM, Spinar J, Theroux P, Wiviott SD, Strony J, Murphy SA; TRA 2P–TIMI 50 Steering Committee and Investigators. N Engl J Med. 2012 Apr 12;366(15):1404-13.

Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Hankey GJ, Patel MR, Stevens SR, Becker RC, Breithardt G, Carolei A, Diener HC, Donnan GA, Halperin JL, Mahaffey KW, Mas JL, Massaro A, Norrving B, Nessel CC, Paolini JF, Roine RO, Singer DE, Wong L, Califf RM, Fox KA, Hacke W; ROCKET AF Steering Committee Investigators. Lancet Neurol. 2012 Apr;11(4):315-22.

Time for a neurorestorative therapy in stroke. Jäkälä P, Jolkkonen J. Expert Opin Biol Ther. 2012 Mar;12(3):267-70.

Experimental approaches to study functional recovery following cerebral ischemia. Lipsanen A, Jolkkonen J. Cell Mol Life Sci 68:3007-17, 2011.

Cognitive impairment with vascular impairment and degeneration. Pluta R, Jolkkonen J, Cuzzocrea S, Pedata F, Cechetto D, Popa-Wagner A. Curr Neurovasc Res 8:342-50, 2011.

Complex pathology in the thalamus following cerebral ischemia. Hiltunen M, Jolkkonen J. In: Thalamus: Anatomy, Functions and Disorders, ed. Song JL. Nova Science Publishers, Inc, 83-98, 2011.

Chronic hyperperfusion and angiogenesis follow sub-acute hypoperfusion in the thalamus of rats with focal cerebral ischemia. Hayward NMEA, Yanev Y, Haapasalo AK, Miettinen R, Hiltunen M, Gröhn O, Jolkkonen J. J Cereb Blood Flow Metab 31:1119-32, 2011.

Chronic ibuprofen treatment does not affect the secondary pathology in the thalamus or improve behavioral outcome in middle cerebral artery occlusion rats. Lipsanen A, Hiltunen M, Jolkkonen J. Pharmacol Biochem Behav 99:468-74, 2011.

Prevalence of pulmonary embolism in patients with suspected cardioembolic ischemic stroke. Sipola P, Hedman M, Jäkälä P, Karjalainen AM, Peuhkurinen K, Manninen H, Vanninen R. J Thorac Imaging. 2011 Feb;26(1):32-5.

Enhanced angiogenesis and neuroprotection by vascular endothelial growth factor D is not translated to behavioral outcome in a rat model of ischemic stroke. Yanev P, Jolkkonen J, Airenne KJ, Ylä-Herttuala S, Wirth T. J Exp Stroke Trans Med 3:1-14, 2010.

Endovascular treatment of carotid and vertebral arteries. Ikäheimonen K, Vanninen R, Jäkälä P, Mäkinen K, Manninen H. Duodecim. 2010;126(8):945-55. Review. Finnish.

Transplantation of human embryonic stem cell (hESC)-derived neural precursor cells and enriched environment after cortical stroke in rats: cell survival and functional recovery. Hicks AU, Lappalainen RS, Narkilahti S, Suuronen R, Corbett D, Sivenius J, Hovatta O, Jolkkonen J. Eur J Neurosci 29: 562-572, 2009.

Cell-based therapies and functional outcome in experimental stroke. Hicks A, Schallert T, Jolkkonen J.  Cell Stem Cell 5: 139-140, 2009.

Effects of intensive therapy using gait trainer or floor walking exercises early after stroke. Peurala SH,Tarkka IM, Juhakoski M, sandell K, Jäkälä P, Airaksinen O, Sivenius J. J. Rehab. Res., 41:166-173, 2009.

Malignant cerebral infarction and hemicraniectomy. Simula S, Koivisto T, Rinne J, Vanninen R, Jäkälä P. Duodecim. 2009;125(24):2729-38. Finnish.

CNS-active drugs in aging population at high risk of cerebrovascular events: Evidence from preclinical and clinical studies. Zhao Cs, Hartikainen S, Schallert T, Sivenius J, Jolkkonen J. Neuroscience & Biobehavioral Reviews, 32: 56-71, 2008.

Coaccumulation of calcium and beta-amyloid in the thalamus after transient middle cerebral artery occlusion in rats. Mäkinen S, Van Groen T, Clarke J, Thornell A, Corbett D, Hiltunen M, Soininen H, Jolkkonen J. J Cereb Blood Flow Metab 28: 263-8, 2008.

Restoration of normal cortical excitability and gait ability in acute stroke after intensive rehabilitation. Peurala SH, Tarkka IM, Juhakoski M, Könönen M, Karhu J,  Jäkälä P, Vanninen R, Sivenius J. Cerebrovasc Dis., 26(2):208-9; 2008.

Effects of intensive gait-oriented physiotherapy during early acute phase of stroke. Peurala SH, Airaksinen O, Jäkälä P, Tarkka IM, Sivenius J. J Rehabil Res Dev., 44(5);637-48; 2007.

Overexpression of APP provides neuroprotection in the absence of functional benefit following middle cerebral artery occlusion in rats. Clarke J, Thornell A, Corbett D, Soininen H, Hiltunen M, Jolkkonen J. Eur J Neurosci 26:1845-52, 2007. 

Abnormal compartmentalization of norepinephrine in mouse dentate gyrus in alpha-synuclein knockout and A30P transgenic mice. Yavich L, Jäkälä P, Tanila H. J Neurochem, 99(3):724-32; 2006.

Cardiogenic brain embolisms. Halinen M, Jäkälä P, Sipola P, Tapiola T, Mustonen P, Kokkonen J. Duodecim. 2005;121(18):1961-8. Review. Finnish.

Transformation of diffuse β-amyloid precursor protein and b-amyloid deposits to plaques in the thalamus following transient occlusion of the middle cerebral artery in rats. van Groen T, Puurunen K, Mäki H-M, Sivenius J, Jolkkonen J. Stroke 36:1551-1556, 2005.

  • Drug treatment trials (acute phase, secondary prevention)