Sustained sensorimotor impairments after endothelin-1 induced focal cerebral ischemia (stroke) in aged rats.
Despite recent advances, stroke remains a leading cause of neurological disability with the vast majority of victims being the elderly, who exhibit more severe neurological deficits and a reduced capacity to recover from these disabilities in comparison to young stroke survivors. The objective of the present study was to develop a model of focal ischemic stroke in aged rats using endothelin-1 (ET-1) to produce low mortality rates as well as reliable, robust sensorimotor deficits that resemble functional impairments associated with stroke in humans. Here, we studied the functional and histological outcome following unilateral ET-1 infusions into the sensorimotor cortex of aged rats (20-23 months old). This procedure resulted in low mortality rates (13.3%) and no loss in body weight one week following surgery. Functional assessment was performed using a number of reliable behavioural tests: staircase test (fine motor function), horizontal ladder (skilled locomotion), bilateral tactile stimulation test (somatosensory function) and cylinder test (postural weight support). Following ET-1 induced stroke, all tests demonstrated large and sustained sensorimotor deficits in both forelimb and hindlimb function that failed to improve over the 28-day testing period. In addition, histological assessment revealed a substantial loss of retrogradely labelled corticospinal neurons in the ipsilesional hemisphere following stroke. Our results establish a model for the use of aged rats in future preclinical studies, which will enhance assessment of the long-term benefit of potential neural repair and regenerative strategies.
Soleman
Sara
S
Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, 16-18 Newcomen Street, London, SE1 1UL, UK.
Yip
Ping
P
Leasure
J Leigh
JL
Moon
Lawrence
L
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000139:chemically induced* / Q000150:complications* / Q000401:mortality / Q000473:pathology; D004195:Disease Models, Animal; D019332:Endothelin-1; D007839:Functional Laterality / Q000502:physiology; D020233:Gait Disorders, Neurologic / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010812:Physical Stimulation / Q000379:methods; D011597:Psychomotor Performance / Q000187:drug effects; D011712:Pyramidal Tracts / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D019332:Endothelin-1