Ischemic preconditioning procedure induces behavioral deficits in the absence of brain injury?
Preconditioning describes a phenomenon whereby a sub-injury inducing insult can protect against a later larger injury. Thus, short-term cerebral ischemia can protect against a prolonged ischemia (ischemic preconditioning). This study examines rats undergoing ischemic preconditioning to test whether preconditioning may cause changes in behavior even though they do not cause an identifiable brain lesion. Rats had a transient (15 minutes) middle cerebral artery occlusion or a sham occlusion. Forelimb placing and forelimb use asymmetry tests were used to assess behavioral deficits. Brain histology, microglia activation, heat shock protein and ferritin levels were also examined. Ischemic preconditioning did not cause brain infarction, but induced behavioral changes. There were no significant differences between ischemic preconditioning and sham rats in the two behavioral tests at day one. However, the ischemic preconditioning group showed impaired forelimb placing at days 3, 7 and 14 (p<0.05). That group also had a significant (p<0.05) behavioral deficit in the forelimb use asymmetry test at days 3 and 7 (but not 14). Our present study demonstrated that a behavioral deficit occurred in ischemic preconditioning. This raises the question of whether induction of protective mechanisms by preconditioning stimuli necessarily involves some form of brain injury, detectable by changes in behavior though not by a lesion. This would be consistent with data suggesting that brain injury can initiate mechanisms potentially favorable to neuroplasticity and neuroprotection.
Hua
Ya
Y
Department of Neurosurgery, University of Michigan, R5550 Kresge I, Ann Arbor, MI 48109-0532, USA. yahua@umich.edu
Wu
Jimin
J
Pecina
Susana
S
Yang
Shuxu
S
Schallert
Timothy
T
Keep
Richard F
RF
Xi
Guohua
G
D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D039481:CD11b Antigen / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D005552:Forelimb / Q000294:innervation / Q000503:physiopathology; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D019194:Ischemic Preconditioning / Q000009:adverse effects*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D001523:Mental Disorders / Q000209:etiology*; D009363:Neoplasm Proteins / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling / Q000379:methods; D018709:Statistics, Nonparametric; D013778:Tetrazolium Salts; D013997:Time Factors
D039481:CD11b Antigen; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D005293:Ferritins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1