Docosahexaenoic acid complexed to albumin provides neuroprotection after experimental stroke in aged rats.
Recently we have shown that docosahexaenoic acid complexed to albumin (DHA-Alb) is neuroprotective after experimental stroke in young rats. The purpose of this study was to determine whether treatment with DHA-Alb would be protective in aged rats after focal cerebral ischemia. Isoflurane/nitrous oxide-anesthetized normothermic (brain temperature 36-36.5°C) Sprague-Dawley aged rats (18-months old) received 2h middle cerebral artery occlusion (MCAo) by poly-l-lysine-coated intraluminal suture. The neurological status was evaluated during occlusion (60min) and on days 1, 2, 3 and 7 after MCAo; a grading scale of 0-12 was employed. DHA (5mg/kg), Alb (0.63g/kg), DHA-Alb (5mg/kg+0.63g/kg) or saline was administered i.v. 3h after onset of stroke (n=8-10 per group). Ex vivo T2-weighted imaging (T2WI) of the brains was conducted on an 11.7T MRI on day 7 and 3D reconstructions were generated. Infarct volumes and number of GFAP (reactive astrocytes), ED-1 (activated microglia/microphages), NeuN (neurons)-positive cells and SMI-71 (positive vessels) were counted in the cortex and striatum at the level of the central lesion. Physiological variables were entirely comparable between groups. Animals treated with DHA-Alb showed significantly improved neurological scores compared to vehicle rats; 33% improvement on day 1; 39% on day 2; 41% on day 3; and 45% on day 7. Total and cortical lesion volumes computed from T2WI were significantly reduced by DHA-Alb treatment (62 and 69%, respectively). In addition, treatment with DHA-Alb reduced cortical and total brain infarction while promoting cell survival. We conclude that DHA-Alb therapy is highly neuroprotective in aged rats following focal cerebral ischemia and has potential for the effective treatment of ischemic stroke in aged individuals.
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Tiffany N
TN
Eady
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Larissa
L
Khoutorova
Department of Pediatrics, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Andre
A
Obenaus
Department of Pediatrics, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Alena
A
Mohd-Yusof
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Nicolas G
NG
Bazan
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Department of Neurosurgery, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. Electronic address: lbelay@lsuhsc.edu.
Ludmila
L
Belayev
D000367:Age Factors; D000418:Albumins / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
D000418:Albumins; D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids
Behavior; Histopathology; Magnetic resonance imaging; Middle cerebral artery occlusion; Rat; Stroke