lithium-chloride and Brain-Edema

In the present study we analyzed aquaporin-4 (AQP4) immunoreactivity in the piriform cortex (PC) and the hippocampus of pilocarpine-induced rat epilepsy model to elucidate the roles of AQP4 in brain edema following status epilepticus (SE). In non-SE-induced animals, AQP4 immunoreactivity was diffusely detected in the PC and the hippocampus. AQP4 immunoreactivity was mainly observed in the endfeet of astrocytes. Following SE the AQP4-deleted area was clearly detected in the PC, not in the hippocampus. Decreases in dystrophin and α-syntrophin immunoreactivities were followed by reduction in AQP4 immunoreactivity. These alterations were accompanied by the development of vasogenic edema and the astroglial loss in the PC. In addition, acetazolamide (an AQP4 inhibitor) treatment exacerbated vasogenic edema and astroglial loss both in the PC and in the hippocampus. These findings suggest that SE may induce impairments of astroglial AQP4 functions via disruption of the dystrophin/α-syntrophin complex that worsen vasogenic edema. Subsequently, vasogenic edema results in extensive astroglial loss that may aggravate vasogenic edema.

Topics: Animals; Aquaporin 4; Astrocytes; Brain Edema; Calcium-Binding Proteins; Cell Count; Cerebral Cortex; Disease Models, Animal; Dystrophin; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hippocampus; Lithium Chloride; Male; Membrane Proteins; Muscle Proteins; Pilocarpine; Rats; Rats, Sprague-Dawley; Status Epilepticus

Male Sprague-Dawley rats received LiCl (5 mEq/kg; sc) or saline 24 h prior to injection of cholinomimetics. Physostigmine (PHY, 0.54-0.80 mg/kg), diisopropylfluorophosphate (DFP, 1.3-2.5 mg/kg), pilocarpine (PIL, 23-30 mg/kg), or saline was injected subcutaneously at time 0. Rats were observed for seizure activity for 2 h, survivors were killed 24 h later and edema was measured in samples from parietal and piriform cortices, dorsal thalmus, and hippocampus. None of the rats pretreated with saline had seizures when given doses of cholinomimetics alone. However, rats pretreated with LiCl had the following incidence of seizures: PHY 68%, DFP 71% and PIL 100%. Rats given cholinomimetic agents alone did not have brain edema. In contrast, all LiCl-pretreated rats that seized had pronounced brain edema which was greatest in the piriform cortex. Thus, these studies demonstrate that LiCl pretreatment potentiates cholinomimetic-induced seizures. Further, cholinomimetic-induced seizures produce brain changes resulting in edema.

Topics: Animals; Brain; Brain Edema; Chlorides; Isoflurophate; Lithium; Lithium Chloride; Male; Organ Specificity; Physostigmine; Pilocarpine; Rats; Rats, Inbred Strains; Reference Values; Seizures