Environmental influences on locomotor recovery following cortical lesions in rats.

Six groups of 8 Charles River male rats with sham or sensorimotor cortex lesions were or were not exposed to an enriched environment that allowed social interaction and a variety of movement experiences for 2 hrs/day for 30 days during the immediate pre- and/or postoperative period. Ss were trained preoperatively to locomote across a narrow elevated runway. Testing on the locomotor task began 31 days after surgery and continued until preoperative performance levels were achieved. Preoperative enrichment had the most potent influence on initial deficit and recovery of locomotion. Ss that were enriched preoperatively failed to demonstrate any deficit postoperatively, and the topology of their hindlimb movement appeared to be normal. In preoperatively impoverished Ss, postoperative enrichment reduced the degree of initial deficit and speeded recovery of locomotion. However, preoperatively impoverished Ss demonstrated an aberrant topology of hindlimb movement even after they were behaviorally recovered. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic administration of ORG 2766 for 6 months produces a subtle impairment in strategic learning by rats

Dysfunctions in serotonergic pathways may underlie several psychiatric disorders. The reuptake of serotonin (5-HT) from synaptic terminals is mediated by a specific transporter (5-HTT). Genetic variation in the gene coding for the 5-HTT protein might be involved in the predisposition to psychiatric disorders. A systematic screening of the whole coding sequence of the 5-HTT gene in mood disorder (MD) and obsessive-compulsive disorder (OCD) patients, as well as in healthy controls, using PCR and denaturing gradient gel electrophoresis (DGGE) revealed the presence of two mutations. The first was in intron 4, and the second was a C-->A transversion leading to an amino-acid exchange (Leu-->Met) in position 255 of the deduced protein sequence. No further occurrence of this substitution was found in an extended sample of patients and controls. Therefore, structural modifications of the 5-HTT gene do not seem to play either a major or minor role in the genetic predisposition to MD or OCD.     

Reinnervation of dentate gyrus by homologous afferents following entorhinal cortical lesions in adult rats

Granule cells of the rat dentate gyrus which are denervated by unilateral destruction of the entorhinal cortex are reinnervated in part by proliferation of surviving pathways from the contralateral entorhinal cortex. The cells of origin of these lesion-induced projections were identified by retrograde labeling with horseradish peroxidase and were the same cell type which normally project to the ipsilateral dentate gyrus     

Sex-related differences in cortical function after medial frontal lesions in rats.

The effects of sex on the performance of 4 spatial mazes (Morris water task, landmark task, radial arm maze, and egocentric radial arm maze) were studied in male and female rats given medial frontal lesions. Operated rats from both sexes were impaired at all of the tasks, but the frontal males were much less impaired than frontal females on the Morris task and the radial arm maze, both of which require animals to use multiple visual-spatial cues for their successful solution. Males also performed better on the egocentric maze. In contrast, frontal females performed better than frontal males at the landmark task, which is best solved by using a single spatial cue. The only sex difference in unoperated rats was a small advantage for females on the egocentric task. The sex differences may reflect an underlying difference in cortical organization or a differential response to cortical lesion in males and females. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal factors influence recovery of function after embryonic brain tissue transplants in adult rats with frontal cortex lesions.

Adult rats with lesions of the medial frontal cortex received implants of frontal cortex taken from embryos on the 19th day of gestation and placed directly into the zone of injury at 7, 14, 30, or 60 days after initial surgery. Another group was given bilateral frontal lesions, followed 20 days later by a second small lesion to enhance the release of putative neurotrophic factors. They then received transplants 7 days after this second operation. All rats began postoperative training on a spatial alternation learning task within 4 days after the implants of fetal tissue. The brain-damaged rats with transplants at 7 or 14 days after surgery significantly improved postoperative acquisition of spatial alternation. Transplants made 30 or 60 days postoperatively had no effect; these groups were as impaired as those with lesions alone. The animals given a second, "priming" lesion after a 20-day delay, followed by implants of fetal brain tissue, performed as poorly as the group with frontal cortex lesions alone. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral effects of GM1 ganglioside treatment and intrahippocampal septal grafts in rats with fimbria-fornix lesions

The monosialoganglioside GM1 is a compound with neurotrophic properties found to foster functional recovery in various paradigms of brain damage. The present experiment examined whether systemic treatment with GM1 may facilitate behavioral recovery in rats with fimbria-fornix lesions and intrahippocampal grafts rich in cholinergic neurons. Among 68 Long-Evans female rats, 46 sustained a bilateral electrolytic lesion of the fimbria and the dorsal fornix and 22 were sham-operated. Fourteen days later, half the lesioned rats were subjected to intrahippocampal grafts of a fetal septal cell suspension. Starting a few hours after lesion surgery and over a 2-month period, half the rats of each surgical treatment group received a daily injection of GM1 (30 mg/kg i.p.), the other half being injected with saline as a control. All rats were subsequently tested for locomotor activity and radial maze learning. The lesions induced locomotor hyperactivity and impaired learning performances in both an uninterrupted and an interrupted radial maze testing procedure. In all rats with surviving grafts, the grafts had provided the hippocampus with a new and dense organotypic acetylcholinesterase-positive innervation pattern which did not differ between saline- and GM1-treated subjects. The scores/performances of the rats that had received only the grafts or only the GM1 treatment did not differ significantly from those of their respective lesion-only counterparts. However, in the radial-arm maze task, the grafted rats given GM1 showed improved learning performances as compared with their saline-treated counterparts: they used more efficient visit patterns under the uninterrupted testing conditions and made fewer errors under the interrupted ones. The results suggest that GM1 treatment or intrahippocampal grafts used separately do not attenuate the lesion-induced behavioral deficits measured in this experiment. However, when GM1 treatment and grafts are used conjointly, both may interact in a manner allowing part of these deficits to be attenuated.     

Depth perception after infant and adult visual neocortical lesions in light- and dark-reared rats

In 2 experiments the behavior of light- and dark-reared infant- and adult-operated striate rats were compared at 20-160 days of age on a visual cliff apparatus in which the depth of the deep side could be varied. Differential depth thresholds revealed that depth discriminative ability did not develop normally following removal of the striate cortex in infancy. Further, infant-operates who were reared in darkness following their operations performed less well than their light-reared, infant-operated counterparts. The infant-operated animals, regardless of their postoperative rearing condition, performed significantly better than did adult-operated animals after comparable post-operative recovery periods and testing. The results are discussed in terms of further specification of the role played by age of operation and by the interaction between visual experience and age of operation.     

Circadian rhythms and partial recovery of regulatory drinking in rats after lateral hypothalamic lesions.

Eight sighted male albino rats that had recovered spontaneous ingestive behavior after lesions of the lateral hypothalamus were challenged with acute injections of hypertonic NaCl administered at different times during the day-night cycle. Nine intact controls were also studied. Following these injections, drinking was observed only during the nighttime. After morning injections Ss frequently waited until nightfall before drinking, whereas Ss injected at night showed much shorter delays in the behavioral response; a similar nocturnal predominance of drinking was seen after food deprivation and in the ad-lib situation. Studies in 6 blind lesioned Ss suggest that these effects were due to an endogenous circadian rhythm. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Possible anatomical basis of recovery of function after neonatal frontal lesions in rats.

Rats given medial frontal lesions on Postnatal Day 1 or Day 10 were trained on the Morris water task on Days 19–21 or Days 56–58. The operated groups were equally impaired at the water task on Days 19–21, but the Day 10 rats had recovered by 56 days. Dendritic arborization and spine density were analyzed in parietal layer II–III pyramidal cells. At Day 60, but not at Day 22, the Day 10 animals had more dendritic spines per unit dendritic length than did the controls or Day 1 rats. Thus, there was functional recovery rather than sparing after frontal lesions at 10 days, and the recovery was correlated with an increase in dendritic spines. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Retrograde degeneration of thalamic neurons in the mediodorsal nucleus after neonatal and adult aspiration lesions of the medial prefrontal cortex in the rat. Implications for mechanisms of functional recovery

The behavioural consequences of neonatal lesions of the frontal cortex are limited as compared with similar lesions performed in adulthood. The present study has investigated, using unbiased quantitative methods with randomized systematic sampling, the total neuronal cell numbers in the mediodorsal nucleus of the thalamus after aspiration lesions of the medial prefrontal cortex performed in neonatal and in adult rats. It was found that the reduction in total cell numbers after neonatal prefrontal cortex lesions was similar to that found after adult cortex lesions. In neonatally lesioned animals the neuronal cell density was significantly increased by 13%, whereas in adult lesioned animals it was unchanged. On the other hand, the volume of the mediodorsal nucleus was reduced by 27% in neonatally, and 20% in adult lesioned animals. Total neuronal cell number of the mediodorsal nucleus was significantly decreased in neonatally as well as in adult lesioned rats, by 14% and 21%, respectively. These findings are discussed in the light of the previously proposed role of the thalamus as a neural substrate of functional sparing after neonatal cortical lesions.     

Differential effects of prefrontal lesions and combined prefrontal and limbic lesions on subsequent learning performance in the cat.

15 cats were given lesions in either the prefrontal cortex alone (n?=?7) or in the prefrontal cortex, anterior thalamus, mamillary bodies, and subiculum (n?=?8) before being tested in the acquisition of visual-reversal, delayed-alternation, and 2-way active-avoidance tasks. Lesioned Ss were compared to 6 unoperated and 4 sham-operated controls. As an extension of E. Irle and H. J. Markowitsch's (see record 1984-19842-001) study, in which triple limbic lesions failed to impair learning behavior of cats, the present study examined the effects of a lesion in the 4th brain structure (in addition to the original triple lesions). Results indicate that, compared with controls, Ss with prefrontal lesions were impaired in the acquisition of the avoidance task. In contrast, Ss with combined lesions were unimpaired in the acquisition of the visual-reversal task, facilitated in the acquisition of the avoidance task, but impaired in the acquisition of the delayed-alternation task. The superior performance Ss with combined lesions is interpreted as due to a lesion-induced functional shift acting on intact brain structures which, prior to massive limbic lesions, remained inhibited. (56 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Upregulation of GABAA-receptor alpha1- and alpha2-subunit mRNAs following ischemic cortical lesions in rats

Focal cortical lesions are associated with a functional downregulation of the GABAergic system in perilesional tissue lasting (at least) several weeks. The molecular mechanisms underlying this phenomenon are still poorly understood. Here we used RT-PCR to investigate whether mRNA-levels of two alpha-subunits of the GABAA-receptor (alpha1- and alpha2-subunits) change following ischemic cortical lesioning. The results show that 7 days after lesion induction mRNA-levels for both the alpha1- and alpha2-subunits are increased threefold in perilesional tissue ipsilateral, but not contralateral to the lesion. Taken together with the results of a previous immunohistochemical study in which a moderate decrease of the alpha1-subunit-protein and no change for the alpha2-subunit [T. Neumann-Haefelin, J.F. Staiger, C. Redecker, K. Zilles, J.M. Fritschy, H. Mohler, O.W. Witte, Immunohistochemical evidence for dysregulation of the GABAergic system ipsilateral to photochemically induced cortical infarcts in rats. Neuroscience (Oxford) 87 (4) (1998) 871-879] was observed, this is interpreted as a partial block of translation in the perilesional tissue surrounding cortical ischemic lesions.     

Double dissociation of spatial impairments and perseveration following selective prefrontal lesions in rats.

Reports results of 2 experiments with 27 male Wistar and 27 male hooded Long-Evans rats. Lesions to the medial frontal cortex produced severe deficits on spatial reversal learning and on delayed response, while lesions of the orbital frontal cortex produced perseverative response tendencies on a differential reinforcement of low rates 20-sec schedule and on barpressing extinction. Results are strikingly similar to those resulting from dorsolateral frontal and orbital frontal lesions, respectively, in rhesus monkeys. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Deficits and recovery of first- and second-order motion perception in patients with unilateral cortical lesions

Unilateral lesions in the posterior parietal cortex can degrade motion perception in the contralesional visual hemifield. Our aim was to investigate whether deficits caused by cortical lesions may be different for first- and second-order motion perception, and to study the time scale of any potential recovery. In nine patients with circumscribed lesions mainly in the parietal and fronto-parietal cortex, thresholds for direction discrimination were measured for stimuli presented peripherally in their ipsi- and contralesional hemifield. Subjects had to identify the direction of a vertically moving object embedded in a background of dynamic random dot noise. The object consisted of various proportions of signal and noise dots. Signal dots were either (a) coherently moving in the same direction as the object (first-order), (b) stationary (second-order: drift-balanced), or (c) coherently moving in the opposite direction (second-order: theta). Noise dots were flickering. Two patients showed significant threshold elevations for all three types of motion stimuli presented in their contralesional hemifield, while thresholds for ipsilesional targets were unaffected. Neither showed any selective deficit of first- versus second-order motion perception, but second-order motion was more impaired. Their lesions probably included the motion area V5-MT, which was spared in the other seven patients. One of the patients, who was retested several times during a 27-month postlesional period, showed complete recovery for first- and second-order motion direction discrimination, as well as for the detection of speed differences.     

Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice

We evaluated ethanol- and HCl-induced mucosal damages in developing rats. The degree of damage induced by ethanol and HCl was greatest in 1-week-old rats and decreased significantly with age until 4 weeks; thereafter it increased again. To evaluate the effect of weaning on the maturational changes in mucosal defense, we compared ethanol-induced mucosal damage among three groups of newborn rats: (1) receiving milk only; (2) receiving only rat chow from 14 days of age, and (3) having free access to milk and chow. There were no significant differences at 18 and 21 days of age. The mucus thickness increased with age until 8 weeks and was not affected by weaning. In conclusion, developmental changes occur in gastric mucosal protection in rats. Weaning does not have a significant effect on these changes.     

Effect of ganglioside (GM1) on memory in senescent rats

We investigated the effects of aerosolized prostacyclin (PGI2) administration on hemodynamics and pulmonary gas exchange in 8 patients with severe respiratory failure and acute pulmonary hypertension. Nebulization of epoprostenol (5 ng/kg body weight for 15 min) decreased mean pulmonary blood pressure from 41.2 +/- 6.7 mm Hg (mean +/- SD, before administration) to 36.1 +/- 6 mm Hg < or = 15 min (p < 0.05). The effect was reversed 10 min after discontinuation of PGI2 (40.9 +/- 6.3 mm Hg). Pulmonary vascular resistance index (339 +/- 138 dynes.s.cm-5.m2, before administration) was significantly (p < 0.05) reduced < or = 15 min (260 +/- 89 dynes.s.cm-5.m2) and increased again after discontinuation of PGI2 (341 +/- 142 dynes.s.cm-5.m2). The ratio of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) increased from 119 +/- 34 mm Hg (before administration) to 163 +/- 76 mm Hg (15 min after initiation of administration p < 0.05) and was reduced after PGI2 discontinuation (116 +/- 35 mm Hg). Heart rate, mean blood pressure, central venous pressure, and pulmonary arterial wedge pressure remained unchanged, whereas cardiac index was slightly reduced. We assume that PGI2 aerosolization is a beneficial technique, applied with a ventilator nebulization system. The beneficial effect might be caused by selective pulmonary vasodilatation in well-ventilated areas of the lung.     

Visual experience, unilateral cortical lesions, and lateralization of function in rats.

Measured the effects of early visual experience and later unilateral neocortical lesions on the behavior of 30 male hooded Long-Evans rats in an open-field, 17-arm spatial maze and on a visual field or perimetry test. 30 Ss were formed into 6 groups—3 light-reared (LR) and 3 dark-reared (DR)—of 5 Ss each in order to receive right-, left-hemisphere, or sham neocortical lesions. The comparison of behavior observed in the open field revealed that LR Ss with right-hemispheric lesions were more active and reared more than any of the other Ss. On the radial-maze task, in which 8 of 17 arms were baited, all Ss with lesions performed less effectively than did sham-operated Ss. The effect of the lesions was significantly greater for LR than for DR Ss. Perimetry testing revealed that, although the lesioned Ss did react to stimuli throughout their visual field, some contralateral neglect was evident in both LR and DR Ss; the lesions had a greater impact on orientation behavior of LR Ss, however. No evidence emerged of any functional asymmetry following the unilateral cortical lesions. Findings are discussed in terms of V. H. Denenberg's (1981) hypothesis about cerebral and functional asymmetry in the rat. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of prefrontal cortex ablation in neonatal, juvenile, and young adult rats.

Long-Evans hooded rats sustaining lesions in the medial (MF) or the orbital (OF) prefrontal cortex at various ages (10, 25, 40, or 60 days postnatally) were tested as adults on a series of behavioral tasks that are known to be sensitive to such lesions in adults. On spatial alternation learning, both the 40- and 60-day MF Ss were seriously impaired, whereas neither the 10- nor the 25-day MF Ss differed from controls. On a hoarding task, 25- and 60-day MF Ss hoarded less food than either controls or 10-day MF Ss. Lesions of OF cortex in males at 40 or 60 days significantly increased running-wheel activity; OF lesions in both sexes at 25 days of age or later decreased the rate of continuous reinforcement reacquisition relative to controls, whereas 10-day OF Ss did not differ from controls on either task. Thus, Ss with lesions of either frontal area at 10 days of age showed complete behavioral sparing on all measures. The effects of lesions at later ages varied with the behavioral task employed and with lesion locus. Although the 10-day Ss received a somewhat longer postoperative recovery interval than most of the later operates, these results cannot be explained on the basis of recovery time alone. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Working memory, response selection, and effortful processing in rats with medial prefrontal lesions.

Examined the effects of lesions of the prelimbic area of the prefrontal cortex on acquisition and retention of nonmatching (NMTS) and matching-to-sample (MTS) tasks. 64 male rats participated. Both tasks involved a reference and a working memory component, but only working memory was impaired by the lesions. A comparison of the 2 tasks revealed quantitatively similar deficits in postoperatively trained rats. In preoperatively trained rats, however, the deficits were more important in the MTS task than in the NMTS task. In addition, an effect of interference between successive trials was observed in the NMTS task but not in the MTS task. Perseverative tendencies were observed in the MTS task only. Results suggest that prefrontal lesions induce working memory deficits as a result of poor temporal encoding and increased susceptibility to interference, and impair effortful processing, such as that engaged in response selection mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relatively brief environmental enrichment aids recovery of learning capacity and alters brain measures after postweaning brain lesions in rats.

Two experiments showed that enriched postlesion experience aided in overcoming effects of simultaneous bilateral cerebral lesions made at 30 days of age in 64 male inbred Fischer rats (Exp I) and 60 male Berkeley S-sub-1 rats (Exp II). The lesions were directed to the occipital cortex, but in most cases there was also some impairment of the hippocampus. For 60 days after operations, half of the Ss lived in small individual cages and half lived in groups in large enriched-environment cages. They were then pretrained and tested on the standard 12 Hebb-Williams problems. Daily injections of methamphetamine (vs saline) during the period of differential experience in Exp I had no effect on the behavioral scores. Exp II included groups that received only 2 hrs/day of enriched experience, and they benefited as much as groups that remained in the enriched environment 24 hrs/day. Results demonstrate significant beneficial effects of environment when bilateral lesions were made at a later age and when the periods of enriched experience were shorter than have previously been tested. Two additional experiments with 112 Berkeley S-sub-1 rats revealed significant effects of both lesions and environment on weight and RNA/DNA of brain regions. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)