Long-term functional consequences of transient occlusion of the middle cerebral artery in rats: a 1-year follow-up of the development of epileptogenesis and memory impairment in relation to sensorimotor deficits.
Post-stroke seizures occur in 5-20% of patients. Modeling of stroke-induced seizures in animals provides a useful tool for investigating the molecular basis of epileptogenesis and for developing therapies for stroke patients at increased risk for epileptogenesis. The questions addressed in the study were: (1) Do rats develop spontaneous seizures after transient occlusion of the middle cerebral artery (MCAO)? (2) Is epileptogenesis associated with impaired hippocampus-dependent spatial learning and memory? (3) Are the functional abnormalities linked to axonal plasticity in the dentate gyrus? (4) Does the sensorimotor impairment induced by MCAO predict the risk of epileptogenesis? Adult male Sprague-Dawley rats were subjected to MCAO for 120 min. Development of spontaneous seizures was monitored by 1 week of continuous video-electroencephalographic (EEG) recordings at 3, 7, and 12 months after MCAO. Spontaneous seizures were not detected during 1-year follow-up in ischemic rats. Animals were, however, impaired in the spatial memory task (P<0.001), which was not associated with altered hippocampal LTP or abnormal mossy fiber sprouting (Timm staining). Animals also had a long-lasting sensorimotor deficit (P<0.05). The present study indicates that MCAO causes long-lasting sensorimotor and spatial memory impairment, but does not induce epileptogenesis or spontaneous seizures.
Department of Neuroscience and Neurology and Al Virtanen Institute, University of Kuopio, P.O. Box 1627, Kuopio 70211, Finland.
Heli
H
Karhunen
Asla
A
Pitkänen
Tiina
T
Virtanen
Irina
I
Gureviciene
Raimo
R
Pussinen
Aarne
A
Ylinen
Juhani
J
Sivenius
Jari
J
Nissinen
Jukka
J
Jolkkonen
D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D007859:Learning Disabilities / Q000209:etiology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology* / Q000523:psychology; D020768:Middle Cerebral Artery / Q000502:physiology*; D019599:Mossy Fibers, Hippocampal / Q000473:pathology; D009069:Movement Disorders / Q000209:etiology* / Q000523:psychology; D009473:Neuronal Plasticity / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020886:Somatosensory Disorders / Q000209:etiology* / Q000523:psychology