Basic NeuroscienceLongitudinal assessment of infarct progression, brain metabolism and behavior following anterior cerebral artery occlusion in rats

- We established an endothelin-1 model of anterior cerebral artery occlusion (ACAo).
- Autoradiography and PET disclosed transient gradual ischemia of up to 4 h.
- Comparable to abulia in humans, goal-directed executive functions deteriorated.
- In contrast, hyperactivity predominated, if task-related stimuli were absent.
- The model is well suited to study functional impairment and recovery after ACAo.

BackgroundStroke patients suffering from occlusion of the anterior cerebral artery (ACAo) develop cognitive and executive deficits. Experimental models to investigate such functional impairments and recovery are rare and not satisfyingly validated.New methodWe stereotactically injected the vasoconstrictor endothelin-1 (ET-1) close to the ACA of rats and assessed magnitude and course of CBF reduction using [14C]iodoantipyrine autoradiography and [15O]H2O-PET. [18F]FDG-PET and T2-weighted MRI determined regional metabolic and structural alterations. To test cognitive and executive functions, we analyzed decision-making in a food-carrying task, spatial working memory in a spontaneous alternation task and anxiety in an elevated plus maze test before and 1 month after ACAo.ResultsCBF decreased immediately after ET-1 injection, started to recover 1-2 h and returned to control 4 h thereafter. Metabolic and structural lesions developed permanently in the ACA territory. Hypometabolism occurring bilaterally in the piriform region may reflect diaschisis. Behavioral testing after ACAo revealed context-dependent changes in decision making, exploratory activity and walking speed, as well as decreased anxiety and spatial working memory.Comparison with existing method(s)Aside from modeling a known entity of stroke patients, ACAo in rats allows to longitudinally study deterioration of cognitive and executive function without major interference by disturbed primary motor function. It complements therefore stroke research since common models using middle cerebral artery occlusion (MCAo) all affect motor function severely.ConclusionThe established ACAo model in rats effectively reflects deficits characteristic for ACA stroke in humans. It is furthermore highly suitable for longitudinal assessment of cognitive and executive functions.