Acetylcholinesterase Activity in the Mongolian Gerbil Brain after Acute Poisoning with Aluminum.

The aim of the present study was to evaluate the acetylcholinesterase activity in the brain of adult gerbils (Meriones unguiculatus) treated with aluminum. AlCl3 x 6H2O was given "per os" in the amount of 3.7 g/kg body weight. The animals were killed 24, 48, 72 and 96 hours after the treatment. The activities of acetylholinesterase in the mitochondrial and microsomal fractions of cortex, hippocampus and thalamus as well as plasma levels of aluminum were measured. Acetylcholinesterase activity was significantly reduced in the mitochondrial and microsomal fraction of all investigated structures. Decrease of the enzyme activity was observed in the first 24 hours, and it was most prominent 48 hours after the administration of aluminum in the mitochondrial fractions when the activity of the enzyme was 31%, 29% and 18.9% of the control value, and after 24 hours in the microsomal fractions when the activity of the enzyme was 43%, 48% and 32% of the control value in the cortex, hippocampus and thalamus, respectively. 96 hours after the administration of aluminum the activity of the enzyme was 63%, 57% and 31% of the value in the control group in mitochondrial, and 100%, 80% and 73% of the control value in microsomal fractions in cortex, hippocampus and thalamus. Plasma levels of aluminum were significantly elevated 24 hours after administration of aluminum. After 48 hours the values were doubled in comparison with the control, 72 hours later plasma concentrations of aluminum were decreased, and after 96 hours they reached the value in the control group. We can conclude that a single oral dose (LD50) of aluminum causes the changes in the brain acetylcholinesterase activity. The changes are still present when the aluminum concentration in plasma is normalized.

Liposome-entrapped superoxide dismutase reduces ischemia/reperfusion 'oxidative stress' in gerbil brain.

Bilateral common carotid artery occlusion (15 min.) followed by two hours of recirculation reduced mitochondrial superoxide dismutase (SOD) and glutathione reductase (GR) activities, and increased susceptibility of mitochondrial membranes to in vitro lipid peroxidation in brain regions (i.e., cortex, striatum and hippocampus) of Mongolian gerbil. Intraperitoneal bolus injection (2 mg/kg b.w.) of liposome-entrapped CuZn superoxide dismutase (1-SOD) increased the endogenous SOD activity in normal brain tissue and, when given at the end of ischemia, counteracted both the ischemic reduction of endogenous SOD and the increased peroxidation of mitochondrial membranes. 1-SOD treatment was ineffective in reducing brain swelling, suggesting that superoxide radicals are not a main participant in the process of (post)ischemic brain edema formation.

'Therapeutic window's for multiple drug treatment of experimental cerebral ischemia in gerbils.

The effects of the following drugs: nimodipine (1 mg/kg b.w., i.p.), 2-amino-5-phosphonovaleric acid (4 mg/kg b.w., i.p.) and propentofylline (25 mg/kg b.w., i.p.), administered (alone or in combination) at the end of 15 min bilateral ischemia in gerbils were evaluated on mitochondrial superoxide dismutase (SOD), glutathione reductase (GR), glucose-6 phosphate dehydrogenase (G6PD), monoamine oxidase (MAO) activities, and thiobarbituric acid reactive material (TBARM), and brain water content at 1 hour of reperfusion. The combined treatment virtually abolished early postischemic brain edema (4.1% v.s. 0.6%) and efficiently counteracted ischemia-induced changes [decreased SOD (79% v.s. 98%), GR (52% v.s. 105%) and MAO (25% v.s. 79%), and increased TBARM (198% v.s. 108%)]. The same combination of drugs administered 15 min before ischemia had a similar effect (e.g., reduced brain swelling and lipid peroxidation) as when given at the end of ischemia, whereas a limited or absent impact was seen when the drugs were given 15 min or 1 hour after ischemia, respectively. The data suggest that (post)ischemic brain swelling and mitochondrial dysfunction can be reduced by drugs which synchronously prevent processes induced in the early stages of reperfusion.

Excitatory amino acid receptors, oxido-reductive processes and brain oedema following transient ischaemia in gerbils.

A key mechanism of brain injury after cerebral ischaemia is supposed to be the iron-dependent formation of highly reactive oxygen free radicals initiated by the intracellular accumulation of calcium and promoted by the excess release of glutamate. Oxido-reductive processes (formation of superoxide radicals and lipid peroxidation) are mediated through NMDA-receptors, while non-NMDA receptors, associated with (or being a part of) Na,K-ATPase, are responsible for postischaemic brain swelling. The hypothesis was put forward for consideration that release of glutamate (and other related endogenous excitatory amino acids) due to depolarization in the early minutes of ischaemia and (non)-NMDA antagonists may have roles in the development and prevention of metabolic brain impairment and cytotoxic oedema, respectively, in the ischaemic state.

Monoamines and related enzymes in cerebral cortex and basal ganglia following transient ischemia in gerbils.

The post-ischemic effects on cerebral cortex and basal ganglia monoamine levels and monoamine oxidase (MAO A and B) and catechol-O-methyl transferase (COMT) activities were evaluated in Mongolian gerbils (Meriones unguiculatus) subjected to bilateral common carotid arteries of occlusion for 15 min and reflow for 7 days. Disorders of monoamine metabolism was found in ischemic brain which persisted during the long-term post-ischemia. A rebound increase of norepinephrine and serotonin appeared in early stages (up to 1 h) of post-ischemia both in cerebral cortex and basal ganglia; a rebound increase of dopamine as found only in cerebral cortex. Thereafter, the serotonin level ws enhanced over the control level during the whole post-ischemic period whereas the levels of catecholamines were reduced particularly in basal ganglia. With respect to monoamine content and activities of monoamine degraded enzymes an oscillatory behavior was observed in the post-ischemia. Disorder of the monoamine metabolism found during post-ischemic period possibly contributes to neurological dysfunction after an ischemic insult.