Long-Term Cognitive Deficits After Subarachnoid Hemorrhage in Rats.

BACKGROUND: Cognitive dysfunction can be a long-term complication following subarachnoid hemorrhage (SAH). Preclinical models have been variously characterized to emulate this disorder. This study was designed to directly compare long-term cognitive deficits in the context of similar levels of insult severity in the cisterna magna double-blood (DB) injection versus prechiasmatic blood (PB) injection SAH models. METHODS: Pilot work identified blood injectate volumes necessary to provide similar mortality rates (20-25 %). Rats were then randomly assigned to DB or PB insults. Saline injection and naïve rats were used as controls. Functional and cognitive outcome was assessed over 35 days. RESULTS: DB and PB caused similar transient rotarod deficits. PB rats exhibited decreased anxiety behavior on the elevated plus maze, while anxiety was increased in DB. DB and PB caused differential deficits in the novel object recognition and novel object location tasks. Morris water maze performance was similarly altered in both models (decreased escape latency and increased swimming speed). SAH caused histologic damage in the medial prefrontal cortex, perirhinal cortex, and hippocampal CA1, although severity of injury in the respective regions differed between DB and PB. CONCLUSION: Both SAH models caused long-term cognitive deficits in the context of similar insult severity. Cognitive deficits differed between the two models, as did distribution of histologic injury. Each model offers unique properties and both models may be useful for study of SAH-induced cognitive deficits.

Preclinical animal anxiety research - flaws and prejudices.

The current tests of anxiety in mice and rats used in preclinical research include the elevated plus-maze (EPM) or zero-maze (EZM), the light/dark box (LDB), and the open-field (OF). They are currently very popular, and despite their poor achievements, they continue to exert considerable constraints on the development of novel approaches. Hence, a novel anxiety test needs to be compared with these traditional tests, and assessed against various factors that were identified as a source of their inconsistent and contradictory results. These constraints are very costly, and they are in most cases useless as they originate from flawed methodologies. In the present report, we argue that the EPM or EZM, LDB, and OF do not provide unequivocal measures of anxiety; that there is no evidence of motivation conflict involved in these tests. They can be considered at best, tests of natural preference for unlit and/or enclosed spaces. We also argued that pharmacological validation of a behavioral test is an inappropriate approach; it stems from the confusion of animal models of human behavior with animal models of pathophysiology. A behavioral test is developed to detect not to produce symptoms, and a drug is used to validate an identified physiological target. In order to overcome the major methodological flaws in animal anxiety studies, we proposed an open space anxiety test, a 3D maze, which is described here with highlights of its various advantages over to the traditional tests.

Effects of exposure to extremely low-frequency magnetic field of 2 G intensity on memory and corticosterone level in rats.

In the present study, we examined the effects of chronic exposure (1 and 2 weeks) to an extremely low-frequency magnetic field (ELFMF) of 2 G intensity on memory in rats using an object recognition task. Comparable groups of rats were exposed for 1, 2 or 4 weeks to ELFMF and the following day blood samples were collected from each rat for the measurement of corticosterone level. Our results demonstrate that exposure to ELFMF induces a significant increase in the level of corticosterone in blood plasma and is associated with impairment in discrimination between familiar and novel objects.

Open space anxiety test in rodents: the elevated platform with steep slopes.

This report describes a behavioral test protocol for assessing anxiety in mice and rats in single or multiple sessions. The test is based on exposure of animals to an open-space elevated platform with suspended steep slopes attached on two opposite sides. In this test, all animals cross frequently onto and spend more time in the areas adjacent to slopes than in the areas adjacent to a void space. Balb/c mice (albinos) were shown consistently to be more anxious than CD-1 mice (albinos), c57/Bl6J and c57/Bl6N (pigmented) mice; they do not cross onto the slopes. When Balb/c mice are treated with amphetamine or diazepam, the number of crossings on the platform is significantly increased but only diazepam-treated mice do cross onto the slopes. In the presence of a protected space on the platform, the behavior of c57/Bl6J compares to that of Balb/c mice; they stop crossings onto the slopes and demonstrate avoidance response. Unlike the current existing tests, the present open-space anxiety test demonstrates reliable and consistent results with strong construct and discriminant validity. It provides unequivocal measures of fear-induced anxiety, which are not confounded with measures of fear-induced escape/avoidance responses, hyperactivity or impulsive responses.