Plastic Changes and Disease‐modifying Effects of Scopolamine in the Pilocarpine Model of Epilepsy in Rats

Abstract

Summary: Purpose:We describe the use of a clinically relevant pharmacological intervention that alters the clinical history of status epilepticus (SE)-induced spontaneous recurrent seizures (SRS) in the pilocarpine model and the possible plastic changes underlying such an effect.Methods: Two hours after pilocarpine-induced SE (320-350 mg/kg, i.p.), rats received scopolamine 1-2 mg/kg i.p. or saline, every 6 h for 3 days. After that, osmotic minipumps were implanted for continuous delivery of scopolamine or saline for an additional 14 days. Animals were video-monitored for 12 h/week during the following 3-month period for the occurrence of SRS and, thereafter, were perfused, processed, and coronal brain sections were stained for acetylcholinesterase (AChE) and for the presence of supragranular mossy fibers (Timm).Results: Treatment with scopolamine led to significantly fewer SRS. Staining for AChE in the dentate gyrus was significantly more intense in naïve animals. The scopolamine group had the least intense AChE staining of all groups. However, regression analysis of the AChE staining for this group did not correlate with the presence or absence of SRS, or the latency or frequency of SRS. Supragranular mossy fiber sprouting developed in all animals experiencing pilocarpine-induced SE, irrespective of whether or not they were treated with scopolamine.Conclusions: Pilocarpine-induced SE in the presence of scopolamine might produce animals that, despite mossy fiber sprouting, were not seen to exhibit spontaneous seizures. In addition, our data suggest that the encountered changes in the AChE staining in the dentate gyrus that followed treatment with scopolamine do not help to explain its disease-modifying effects.

Modeling of post-traumatic epilepsy and experimental research aimed at its prevention

“…Research from our group has provided evidence that anticholinergic agents might provide an effective means to modify disease progression in the pilocarpine model of epilepsy ( 89 , 90 ). The administration of scopolamine starting 3 h after the onset of pilocarpine-induced SE was effective in altering epileptogenesis ( 90 ).…”

“…Research from our group has provided evidence that anticholinergic agents might provide an effective means to modify disease progression in the pilocarpine model of epilepsy ( 89 , 90 ). The administration of scopolamine starting 3 h after the onset of pilocarpine-induced SE was effective in altering epileptogenesis ( 90 ). Similarly, in a more extensive study, the administration of biperiden (another cholinergic antagonist) was also shown to be effective in altering disease progression in the same model ( 89 ).…”

Pharmacological Investigations of Selected Multitarget‐Direct Ligands for the Treatment of Alzheimer's Disease

“…Clinically, the hypoactivity of the cholinergic system is one of the important pathological hallmarks observed in AD patients [11] . The cholinergic system is reported to play an important role in cognition and memory formation [12–14] . Further, it has been suggested that the innervations of the cholinergic neurons within hippocampus is responsible for learning and memory [15,16] and the decline in the cholinergic function is associated with cognitive deficit.…”

Melatonin Improves Cognitive Deficits via Restoration of Cholinergic Dysfunction in a Mouse Model of Scopolamine-Induced Amnesia

“…The cholinergic system in the hippocampus plays a crucial role in memory formation and cognition, and a reduction in its function is correlated with AD, resulting in cognitive impairment. − Cholinergic neurons, which use the neurotransmitter acetylcholine (ACh), are within the nucleus basalis and septal diagonal band complex of the basal forebrain, and provide the main source of cholinergic innervation to the hippocampus as well as the cerebral cortex, playing a key role in attention and memory function. , …”