Failure in learning task and loss of cortical cholinergic fibers in microsphere-embolized rats

Abstract

The present study was undertaken to elucidate the pathological changes in learning and memory functions and in the metabolism of cortical cholinergic neurons following microsphere embolism in the rat. Microspheres (48 microm) were injected into the right internal carotid artery of rats. Learning and memory functions were measured 7 or more days after the embolism by active and passive avoidance, and water maze tasks. In the biochemical study, cortical acetylcholine and choline contents, and choline acetyltransferase activity were measured. Cortical acetylcholinesterase-containing fibers were quantitatively estimated in the embolized rat. The active and passive avoidance, and water maze tasks were impaired in the microsphere-embolized rat. In the histochemical study, the density of cortical acetylcholinesterase-containing fibers of the ipsilateral hemisphere of the microsphere-embolized rat was decreased, but cell density was unchanged. Furthermore, microsphere embolism decreased the cortical acetylcholine concentration and choline acetyltransferase activity and increased the choline concentration. The results suggest that microsphere embolism causes severe damage to cortical cholinergic neurons, which may be, at least in part, related to the impairment of learning and memory functions in the sustained brain ischemia.

Models and mechanisms of vascular dementia

“…These ischemic damages resulted in cognitive impairment. Long escape latency was observed in the water maze test about a week after intravascular embolization, suggesting spatial learning impairment and poor performance in the active and passive avoidance [83, 84]. Cerebral embolization as a model for VaD has been advocated also due to its induction of learning impairments in 3 tasks including one trial active and passive avoidance task as well as two-way active avoidance response in a shuttle box, and the water filled multiple T-maze task [85].…”

Unilateral intracarotid injection of holmium microspheres to induce bilateral MRI-validated cerebral embolization in rats

“…The solution was warmed to 37 • C just before reaching the tip of the cannula, thus ensuring delivery into the carotid artery. In many experiments, dextran is used as vehicle of choice (Miyake et al, 1993;Takagi et al, 1997). However, dextran injections in rats are a model for inflammation and shock (Gulati et al, 1983;Kogure et al, 1986) and we therefore think that direct injection into the cerebral arteries should be avoided.…”

Persistent Effects of Delayed Treatment with Nefiracetam on the Water Maze Task in Rats with Sustained Cerebral Ischemia

“…Thus, this model is considered to mimic focal ischemia-induced human stroke (Lyden et al, 1992) or multi-infarct dementia (Naritomi, 1991). Such irreversible ischemic damage may lead to learning and memory dysfunction (Takagi et al, 1997;Nagakura et al, 2002a) and to impairment of the AC/cAMP/PKA system (Nagakura et al, 2002b), resulting in a significant impairment of the signal transduction connecting to the nuclear cAMP response element-binding protein (CREB) in the ME animal (Nagakura et al, 2002b).…”