Marylou M. Glasier

Gender-specific impairment on Morris water maze task after entorhinal cortex lesion.

After unilateral entorhinal cortex lesion, deficits on a working spatial memory Morris water maze task were examined in male and female rats to determine if gender differences exist in response to hippocampal deafferentation. Brain-damaged males showed a persistent water maze deficit that persisted throughout the 10 days of testing. Brain-damaged females did not. The performance of the injured females was only slightly impaired relative to sham males and females, and was significantly better than males with EC damage. This lack of a water maze deficit in lesion females is hypothesized to be due either to gender differences in sprouting responses or to a more flexible use of multiple cues by females relative to males.

Intraseptal injections of 192 IgG saporin produce deficits for strategy selection in spatial-memory tasks

The involvement of the cholinergic septohippocampal system in strategies used to reach a spatial goal was examined by functionally inactivating this system with infusions of 192 IgG saporin, a potent cholinergic immunotoxin. Rats were initially trained on a win-shift radial arm maze (RAM) task and then given injections of either 192 IgG saporin (LES) or saline vehicle (CON) into the medial septum and vertical limb of the diagonal band. Rats were then retested postoperatively on the RAM to assess whether allocentric spatial strategies used to solve the task were impaired. The results indicated that injections of 192 IgG saporin into the septum of rats produced deficits in allocentric strategies used to locate the spatial goal when retested. In addition, place and response learning was also examined in a modified version of the Morris water maze task. In this task, rats with cholinergic lesions were mildly impaired in their ability to learn a place response. In order to clarify further whether rats may have been relying on allocentric or egocentric learning strategies to locate the platform, a probe trial was given on the final test day in which the visible platform was moved to a new location. Control rats swam either to the new platform location or the old platform location indicating the use of both an allocentric and egocentric response. However, rats with the cholinergic septal lesions swam to the new platform location indicating an egocentric response. Taken together, these results suggest that selective cholinergic lesions of the septum produce deficits in spatial strategies used to locate a spatial goal.

Effects of unilateral entorhinal cortex lesion and ganglioside GM1 treatment on performance in a novel water maze task.

Transient deficits have been reported after unilateral entorhinal cortex (EC) lesion. To determine whether there is a more persistent deficit, adult male Sprague-Dawley rats with electrolytic or sham lesions of the left entorhinal cortex were examined on acquisition of a modified working memory task in the Morris water maze. This delayed matching-to-sample task, with a 1-h intertrial interval, reveals a significant deficit in total distance to platform in both presentation (Trial 1) and matching (Trial 2) in the rats with entorhinal lesions. We have also found that this test can be used to assess significant deficits in perseveration (repeated nonproductive movement) in rats with entorhinal lesions. The deficits can be seen up to 16 days postinjury. Administration of ganglioside GM1 resulted in a moderate improvement in performance in both water maze measures analyzed. All groups (sham operated, lesion with saline treatment, and lesion with ganglioside GM1 treatment) were given three other tests, which were used to evaluate possible contributing factors to deficient water maze performance. A one-trial test for exploration of novel objects revealed no significant, simple working memory deficit in any group. Plus maze testing, to assess possible differences in levels of anxiety or increased activity as a component of water maze performance, also revealed no differences in the three groups. All groups were also similar in motor activity, shown by monitoring of activity levels. The worsened water maze performance observed in rats with EC lesion may be related to deficits in working memory ability within the framework of acquisition of a more complex spatial learning task.

A single intraseptal injection of nerve growth factor facilitates radial maze performance following damage to the medial septum in rats

Rats were trained on a radial maze and then given electrolytic lesions of the MS followed by a single intraseptal injection of 5 micrograms of NGF. Three days later they were re-tested on the maze. They were also post-operatively tested for hyperemotionality. MS lesions severely impaired performance on the radial maze and produced increased emotionality. MS lesions also produced a general decrease in hippocampal high affinity choline transport and acetylcholinesterase staining, which was not affected by NGF administration. NGF treatment ameliorated the behavioral deficit in the radial maze but had no effect on the hyperemotionality. In order to determine whether the NGF was working to restore previously learned spatial abilities, the type of learning strategy used by the animals was also assessed. NGF treatment did not restore previously learned spatial strategies but facilitated recovery of alternative learning strategies. The reduction in cognitive deficit was also paralleled by reduced ventricular enlargement in the NGF treated rats. The present results suggest that a single injection of NGF can produce a long-lasting improvement on a cognitive task and reduce some of the injury-induced, secondary reactive changes that occur following electrolytic MS lesions.

Some practical and theoretical issues concerning fetal brain tissue grafts as therapy for brain dysfunctions

Grafts of embryonic neural tissue into the brains of adult patients are currently being used to treat Parkinsons disease and are under serious consideration as therapy for a variety of other degenerative and traumatic disorders. This target article evaluates the use of transplants to promote recovery from brain injury and highlights the kinds of questions and problems that must be addressed before this form of therapy is routinely applied. It has been argued that neural transplantation can promote functional recovery through the replacement of damaged nerve cells, the reestablishment of specific nerve pathwayslost as a result ofinjury, the release of specific neurotransmitters, or the production of factors that promote neuronal growth. The latter two mechanisms, which need not rely on anatomical connections to the host brain, are open to examination for nonsurgical, less intrusive therapeutic use. Certain subjective judgments used to select patients who will receive grafts and in assessment of the outcome of graft therapy make it difficult to evaluate the procedure. In addition, little long-term assessment of transplant efficacy and effect has been done in nonhuman primates. Carefully controlled human studies, with multiple testing paradigms, are also needed to establish the efficacy of transplant therapy.

An Overview of Developments in Research on Recovery from Brain Injury

Although there have recently been many other conferences on the subject, it was in 1981 that Professors van Hof and Mohn, under the auspices of the European Brain and Behaviour Society, organized the first major European workshop devoted exclusively to “Functional Recovery from Brain Damage.” That landmark meeting, held at the Erasmus University in Rotterdam, was the first major international conference bringing together investigators from many different countries who were interested in a careful and thorough analysis of brain damage and the processes mediating behavioral recovery.

GM1 Produces Attenuation of Short-Term Memory Deficits in Hebb–Williams Maze Performance after Unilateral Entorhinal Cortex Lesions

The Hebb-Williams maze was used to examine spatial abilities of adult male Sprague-Dawley rats with unilateral electrolytic entorhinal cortex lesions. The injured rats were treated for 14 days with either saline or ganglioside GM1. Testing was begun 7 weeks following injury, and involved 12 maze problems with independent configurations, with immediate starting replacement used for the six trials per problem. Compared to sham-operated counterparts, the rats with lesion plus saline treatment were impaired in total number of errors, initial entry errors, and repeat errors over 12 consecutive problems. GM1-treated rats showed improved performance, making significantly fewer total and repeat errors, indicating that this substance may be potentially useful as therapy after entorhinal cortex injury.

Effects of unilateral entorhinal cortex lesion on retention of water maze performance

In a previous study, adult male Sprague-Dawley rats with unilateral, electrolytic entorhinal cortex lesions showed significant deficits in acquisition of a water maze task that measured working memory. The 10 days of testing used two trials per day with an intertrial interval of 1 h, and the rats with entorhinal damage were impaired in total distance to the platform in both trials. In the present retention study, rats who learned the same task prior to injury and were then retested for 5 days after lesion showed only a first day deficit in total distance to platform in the second trial. Analysis of swim patterns indicated that rats with unilateral entorhinal lesions used an altered strategy in retention testing to find the platform in the second trial of each day and incorporated the use of headings appropriate for Trial 1 only. This altered or compensatory strategy was not the optimum choice for problem solution. Although the rats then were able to switch headings and find the platform without significant impairment in total distance to platform on days 2-5 of testing, the use of an initial incorrect strategy indicated subtle residual deficits in cue integration and use of working memory.

Pharmacological treatments for brain-injury repair: Progress and prognosis

Abstract It has been only within the last 10 years that research on treatment for central nervous system (CNS) recovery after injury has become more focused on the complexities involved in promoting recovery from brain injury when the CNS is viewed as an integrated and dynamic system. There have been major advances in research in recovery over the last decade, including new information on the mechanics and genetics of metabolism and chemical activity, including the definition of excitotoxic effects and the discovery that the brain secretes complex proteins, peptides, and hormones that are capable of directly stimulating the repair of damaged neurons or blocking some of the degenerative processes caused by the injury cascade. Many of these agents, plus other non-toxic, naturally occurring substances, are being tested as treatment for brain injury. Further work is needed to determine appropriate combinations of treatments and optimum times of administration with respect to the time course of the CNS disorde...

Effects of a single intraseptal injection of NGF on spatial learning in the water maze

Male Sprague-Dawley rats given electrolytic lesions of the septum followed by a single intraseptal injection of 5 microg of NGF were trained on a water maze task that assessed their ability to learn the location of a visible platform and the location of platform when it was submerged. Rats with damage to the septum acquired the visible platform version of the task but were significantly impaired in locating the submerged platform. Administration of NGF, however, produced an intermediate ameliorative effect on the measure of latency to find the hidden platform during these trials. In order to determine the relative strength of the place and cue responses learned during the visible and hidden platform training trials, a probe trial was given on the final test day in which the visible platform was moved to a new location. Control rats swam either to the new platform location or the old platform location indicating the use of both a place and cue response. However, both rats with septal damage alone and rats with septal lesions treated with NGF swam directly to the new platform location indicating the relative strength of the cue response. These results support previous findings indicating that a single injection of NGF can produce improvements on a cognitive task, but it may not be doing so by restoring lost spatial functions following septohippocampal damage.