Estradiol inhibits astrocytic GFAP expression in an animal model of neuroinflammation.

There are many animal models for studying different aspects of neurodegeneration. Lipopolysaccharide (LPS) injected in rats intracerebroventricularly induces neuroinflammation quite similar to the inflammatory component of chronic neurodegenerative conditions such as Alzheimer's disease. We used this model to examine the effect of estradiol on neuroinflammation. LPS or pyrogen-free saline were injected intracerebroventricularly (i.c.v.) into the lateral ventricle of male Wistar rats and estradiol was administered (200 micrograms/kg s.c.) 48 h before or 24 h after LPS injection. LPS-induced body weight loss was partially postponed by the treatment, especially in the rats pretreated with estradiol. When analyzing GFAP glial cell morphology in the CA3c area of the hippocampus and corpus callosum, as well as the number of astroglial cells in CA3c and CA1, GFAP expression was found to be reduced. This was true especially in the animals pretreated with estradiol and to a much lesser extent in the posttreated ones. The data support the possible existence of a neuroimmunomodulatory effect of estradiol administration in neurodegenerative conditions, which influences the inflammatory component.

A post-ischaemic single administration of galanthamine, a cholinesterase inhibitor, improves learning ability in rats.

Transient forebrain ischaemia is widely observed in clinical practice. We have examined the effect of a single administration of the cholinesterase inhibitor galanthamine (2mg kg(-1) i.p.) 25 min after reperfusion in male Sprague-Dawley rats (180 +/- 20 g) after a 20-min common carotid artery occlusion. Twenty-four-hours post-ischaemia there was no difference in motor co-ordination or muscle tonus of the rats treated with or without galanthamine as assessed by the rota-rod test. Learning ability was examined using the shuttle-box test, evaluating the latency time and the number of errors for six days in succession. The performance of the ischaemic saline-injected rats was significantly impaired on days 4, 5, 6 (latency time) compared with the non-ischaemic rats and with the ischaemic animals administered galanthamine (P < 0.05). Similar results were obtained when counting the number of errors (failure to cross the cage during conditioned or unconditioned stimulus). The monitoring of body temperature during the first 12-h post-ischaemia did not show any significant difference between the groups. The data showed a beneficial effect of galanthamine on the recovery of learning ability when administered once only post-ischaemia. This suggests a direct effect on the early pathologic mechanisms of CNS damage. Cholinesterase inhibitors may prove useful in the early clinical treatment of ischaemic conditions.

Effect of the acetylcholinesterase inhibitor galanthamine on learning and memory in prolonged alcohol intake rat model of acetylcholine deficit.

Different cholinomimetics are used in conditions of CNS acetylcholine (ACh) deficit. In this study, we examined the effect of the acetylcholinesterase inhibitor galanthamine in a prolonged alcohol intake model of ACh deficit in male Wistar rats. After 16 weeks of alcohol intake and a 2-week pause, rats administered galanthamine (2.5 mg/kg/day i.p.) showed an improved speed of learning and short-term memory in the shuttle box test as compared to the saline-injected alcoholic group (p < 0.05). Four weeks later, significant improvement in the passive avoidance memory of alcoholic galanthamine-treated rats was noted in the eight-arm radial maze (14 day test duration) as compared to the saline-injected alcoholic group (p < 0.05). During the first week in the shuttle box test, the nonalcoholic galanthamine-treated animals exhibited significantly impaired performance as compared to the untreated nonalcoholic control, while four weeks later, in the eight-arm radial maze, both groups did not differ. Our results show that galanthamine improves the speed of learning, short-term memory and spatial orientation of rats in conditions of prolonged alcohol intake.

Effects of dexamethasone in rat neonatal model of axotomy-induced motoneuronal cell death.

In this study the effect of dexamethasone on the motoneuronal cell death and the nuclear and somatic morphology changes occurring after peripheral nerve transection in the neonatal rats has been determined. The study was performed on 3 day old Wistar rats. Animals were divided into 3 groups--control, axotomised, and axotomised and dexamethasone-treated. The nerve transection was performed bilaterally. A dose of 0.5 mg/kg/24h dexamethasone, administered i.p., was used. On day 7 after the operation the animals were sacrificed and the motoneurons in segments L4 and L5 in the spinal cord were counted and their morphology was analysed. 25. 88% cell loss was found in the axotomised group (p<0.001 vs. control) versus 43.33% cell loss in the dexamethasone-treated and axotomised animals (p<0.01 vs. control). Dexamethasone significantly decreased the number of the surviving motoneurons (p<0.05 vs. axotomised). The axotomised group showed enlargement of the somatic area and the maximal and minimal diameters of the cell while the dexamethasone-treated and axotomised group showed soma shrinkage and decrease in the minimal cell diameter. Our results propose a possible hazard towards the application of dexamethasone in the treatment of new-borns with concomitant nerve injuries.