title: Brain irradiation improves focal cerebral ischemia recovery in aged rats.
abstract: BACKGROUND
  Studies have shown that aging is a significant factor in worsening stroke outcomes. While many mechanisms may aggravate brain injury in the elderly, one such potential system may involve increased glial proliferation in the aged stroke patient that could result in increased scar formation. We hypothesized that in aged rats a single brain-only exposure to a low radiation dose prior to focal brain ischemia would reduce glial proliferation and confer a long-term neuroprotective effect.
  
  
  METHODS
  Brain-only proton irradiation (8 Gy) was performed ten days prior to middle cerebral artery occlusion (MCAO) in aged male rats. Magnetic resonance imaging (MRI) was undertaken in naive, radiation-only (Rad), MCAO, and MCAO+Rad groups at 2, 14 and 28 days post-stroke followed by immunohistochemistry (day 28).
  
  
  RESULTS
  Ischemic lesion volume in MCAO+Rad group was decreased by 50.7% with an accelerated temporal reduction in peri-lesional brain edema and increased water mobility within the ischemic core (39.8%) compared to MCAO-only rats. In the peri-lesional brain region of MCAO+Rad rats there was a decreased scar formation (49%, glial fibrillary acidic protein), brain tissue sclerosis (30%, aquaporin-4) and necrosis/apoptosis (58%, TUNEL positive cells) compared to those in MCAO animals.
  
  
  CONCLUSIONS
  In aged animals a single exposure to brain-only radiation prior to focal cerebral ischemia is neuroprotective as it prevents glial hyperproliferation, progressive brain tissue sclerosis and reduces the apoptosis/necrosis in the peri-lesional region. Decreased lesion volume is in agreement with accelerated reduction of brain edema in these animals.
authors.affiliation: Department of Radiation Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Titova
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ostrowski
authors.forename: Arash
authors.initials: A
authors.lastname: Adami
authors.forename: Jerome
authors.initials: J
authors.lastname: Badaut
authors.forename: Serafin
authors.initials: S
authors.lastname: Lalas
authors.forename: Nirmalya
authors.initials: N
authors.lastname: Ghosh
authors.forename: Roman
authors.initials: R
authors.lastname: Vlkolinsky
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.forename: Andre
authors.initials: A
authors.lastname: Obenaus
mesh_terms: D000375:Aging / Q000528:radiation effects*; D000704:Analysis of Variance; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001921:Brain / Q000502:physiology* / Q000528:radiation effects*; D001929:Brain Edema / Q000209:etiology / Q000532:radiotherapy; D020520:Brain Infarction / Q000209:etiology / Q000532:radiotherapy; D002545:Brain Ischemia / Q000532:radiotherapy*; D001931:Brain Mapping; D002921:Cicatrix / Q000209:etiology / Q000378:metabolism / Q000532:radiotherapy; D016371:Cranial Irradiation / Q000379:methods*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D009460:Neurologic Examination; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000528:radiation effects*; D013997:Time Factors
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein