title: Early rehabilitation aggravates brain damage after stroke via enhanced activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX).
abstract: Although physical exercise has emerged as a potential therapeutic modality for functional deficits following ischemic stroke, the extent of this effect appears to be contingent upon the time of exercise initiation. In the present study, we assessed how exercise timing affected brain damage through hyperglycolysis-associated NADPH oxidase (NOX) activation.
  
  
  
  Using an intraluminal filament, adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2h and assigned to one non-exercise and three exercise groups. Exercise on Rota-rod was initiated for 30min at 6h (considered very early), at 24h (early), and at day 3 (relatively late) after reperfusion. Lactate production was measured 30min after exercise completion, and NOX activity and protein expression of NOX subunits (p47(phox), gp91(phox), p22(phox) and p67(phox)) and glucose transporter 1 and 3 (Glut-1 and -3) were measured at 3 and 24h after exercise. Apoptotic cell death was determined at 24h after exercise.
  
  
  
  Lactate production and Glut-1 and Glut-3 expression were increased after very early exercise (6h), but not after late exercise (3 days), suggesting hyperglycolysis. NOX activity was increased with the initiation of exercise at 6h (P<0.05), but not 24h or 3 days, following stroke. Early (6 and 24h), but not late (3 days), post-stroke exercise was associated with increased (P<0.05) expression of the NOX protein subunit p47(phox), gp91(phox)and p67(phox). This may have led to the enhanced apoptosis observed after early exercise in ischemic rats.
  
  
  
  Hyperglycolysis and NOX activation was associated with an elevation in apoptotic cell death after very early exercise, and the detrimental effect of exercise on stroke recovery began to decrease when exercise was initiated 24h after reperfusion.
authors: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, China; Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors: Jiamei
authors: J
authors: Shen
authors: Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors: Mitchell
authors: M
authors: Huber
authors: Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors: Ethan Y
authors: EY
authors: Zhao
authors: Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors: Changya
authors: C
authors: Peng
authors: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, China.
authors: Fengwu
authors: F
authors: Li
authors: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, China.
authors: Xiaorong
authors: X
authors: Li
authors: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, China; Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: xgeng@med.wayne.edu.
authors: Xiaokun
authors: X
authors: Geng
authors: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, China; Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: yding@med.wayne.edu.
authors: Yuchuan
authors: Y
authors: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000150:complications / Q000201:enzymology* / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D020521:Stroke / Q000150:complications / Q000201:enzymology* / Q000517:prevention & control*
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D019344:Lactic Acid; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1
keywords: Exercise; Glut-1; Glut-3; Hyperglycolysis; Lactic acidosis; Timing