Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of neurological disorders are associated with the loss of specific populations of neurons. Alzheimer's, Parkinson's, and Huntington's diseases present unique constellations of behavioral and neurological abnormalities which result from the degeneration of neurons in specific regions of the brain. Approaches to the treatment of these neurodegenerative disorders have met with either limited or no success. New treatment strategies based upon a better understanding of the inherent mechanisms of neuroplasticity might provide more rational approaches to prevent, limit, or treat these and other neurodegenerative disorders. The development and standardization of appropriate animal models of neurodegenerative disorders will be essential to realize this possibility. Using the cholinergic neurotoxin AF64A we have developed a rodent model of cholinergic hypofunction that exhibits behavioral, anatomical, and neurochemical deficits very analogous to those observed in Alzheimer's disease. Furthermore, we have found that administration of neurotrophic factors, such as ganglioside AGF2, and the transplantation of fetal cholinergic neurons into the hippocampus can attenuate both the behavioral and neurobiological alterations induced by AF64A. These efforts should lead to the development of innovative clinical strategies and they should also help to elucidate the neurobiology of brain injury and recovery of function.
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PMID:Neuroplasticity, the aging brain, and Alzheimer's disease. 150 10

Unilateral lesions of rat entorhinal cortex produce a transitory performance deficit on spatial learning tasks, such as reinforced alternation in a T-maze. Tetrahydroaminoacridine (THA), a cholinesterase inhibitor, was administered to determine its effects on behavioral recovery using a reinforced alternation task in a T-maze. Rate of recovery after unilateral entorhinal lesion was not affected by a low dose of THA (0.05 mg/kg), while a higher dose (5.0 mg/kg) impaired recovery. Behavioral recovery was subsequently evaluated in the same rats following lesions to the contralateral entorhinal cortex. Serial bilateral lesions of the entorhinal cortex are known to produce a prolonged performance deficit on the alternation task. The 0.05 mg/kg THA group exhibited an intermediate rate of recovery, between the undamaged control group and bilateral lesion-saline injected groups. The group receiving 5.0 mg/kg of THA after bilateral lesion did not differ from the bilateral lesion-saline group. The failure of THA to significantly improve functional recovery in rats with lesions of the entorhinal cortex indicates that the compound may have limited applicability in treating human neurodegenerative disorders such as Alzheimer's disease.
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PMID:Effects of tetrahydroaminoacridine (THA) on functional recovery after sequential lesion of the entorhinal cortex. 174 69

The different expressions of mental decline in elderly people, from simple senile benign forgetfulness to SDAT, can be evaluated by psychometric and neurophysiological tests. In the present study, the effects of oxiracetam, piracetam and placebo were compared in a group of elderly subjects. The results of the trial, structured as single blind, clearly showed that nootropics positively effect both clinical and neurophysiological performances and that oxiracetam produces a more pronounced effect when compared to piracetam. In fact, oxiracetam was found more effective in improving psychometric scales such as GDS (clinical performances) as well as the amplitude and the latency of the P300 (neurophysiological performances), which reflect a functional recovery of the cerebral pathways related to attention and memory.
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PMID:A clinical and neurophysiological trial on nootropic drugs in patients with mental decline. 186 25

A computer-assisted morphometric study has been carried out on ethanol phosphotungstic acid (E-PTA) stained synaptic junctions in the human dentate gyrus supragranular layer from adult, old and Alzheimer's disease (AD)-affected patients. The number of synapses per unit volume of tissue (Nv = numerical density), the average area of the single junction (S) and the total area of the synaptic contact zones in a unit volume of tissue (Sv = surface density) were the 3 parameters taken into account. The synapse to neurone ratio was also calculated for each patient. During physiological aging, Nv and Sv significantly decreased and S increased, respectively. In the AD hippocampi, Nv and Sv underwent a further decrease which was in the range of more than 40% with reference to the adult values. S was the same as the old control group. In comparison with the adult values, the number of synapse/neurone decreased by 15.6 and 48% in old and AD patients, respectively. Nv, S and Sv, while reporting on discrete ultrastructural features of the synaptic junctional zones, are closely related to each other and, taken together per group of patients, may represent a reliable index of the morphological adaptive changes taking place at the synapses. Thus, the significant increase of S both in old and AD hippocampi may be regarded as a CNS plastic response to aging and disease, although the marked decrease of Nv and Sv supports that in AD synaptic ultrastructural alterations proceed beyond a critical threshold for functional recovery.
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PMID:Morphological adaptive response of the synaptic junctional zones in the human dentate gyrus during aging and Alzheimer's disease. 237 7

The present paper outlines the reasons for the current interest in work on septo-hippocampal grafts. It examines the role of cholinergic dysfunction in the memory deficits associated with Alzheimer's disease, the effects of hippocampal lesions on memory in infra-human animals, and the anatomy of the hippocampus. Methodological aspects of neural grafting are then examined, including the source, nature and site of the graft. A review of the tasks employed to determine functional recovery following septo-hippocampal grafts suggests that although recovery is evident its nature is unclear. An experiment is described which suggests that grafts from embryonic septum bring about recovery of working memory in rats. Different bases of the recovery of function are discussed, including the role of the graft in eliciting release of trophic factors from the host brain; the possibility that the graft acts by providing a pool of neurotransmitter; and finally that the graft may replace the damaged circuitry of the host. Some problems of the grafting procedure are outlined. It is concluded that grafting may provide a viable treatment technique in the absence of other forms of treatment for Alzheimer's disease.
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PMID:Restoration of memory following septo-hippocampal grafts: a possible treatment for Alzheimer's disease. 267 93

Significant progress has been made over the past decade in utilizing the techniques of neural transplantation to promote regeneration and recovery of function in the mammalian brain. The present paper reviews recent advances in our understanding of the properties and mechanisms of action of neural transplants and discusses how these advances might be applied to designing therapeutic approaches for treating Alzheimer's disease.
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PMID:Neural transplantation: potential therapy for Alzheimer's disease. 331

Rats were trained for several months to perform a radial arm maze task and then given either sham or ibotenic acid lesions of the nucleus basalis magnocellularis (NBM), the primary cholinergic projection to the neocortex. The lesion produced a profound and apparently selective disturbance in memory for recent events. Further testing revealed that although the memory deficit persisted for several weeks, a gradual but complete recovery eventually occurred. Moreover, when these functionally recovered rats were later tested on a passive avoidance task that is normally sensitive to lesions of the NBM, no deficit was found. Thus, the post-lesion recovery of function generalized to a different memory test, upon which no post-lesion practice had been given. Post-mortem determinations revealed that the lesions caused marked neurodegeneration of the NBM, and decreases in both cortical choline acetyltransferase activity and high affinity choline uptake, but had no effect on density of muscarinic receptors. No evidence of neuronal recovery or neurochemical compensatory changes in the cholinergic system was found in the cortical projection areas, lesion site, or in parallel cholinergic systems terminating in the hippocampus or olfactory bulb. These results support the idea that the cortically-projecting cholinergic cells of the NBM normally play an important role in mediating recent memory. However, they also demonstrate that any simple relationship between the function of this brain region and the mediation of recent memory is unlikely. Finally, the results of this study direct attention toward issues related to the mechanisms involved with the recovery of function, and the extent to which degeneration of this brain area may contribute directly to the severe disturbance of cognitive function associated with certain neurodegenerative diseases (e.g., Alzheimer's, Pick's and Parkinson's disease).
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PMID:Selective memory loss following nucleus basalis lesions: long term behavioral recovery despite persistent cholinergic deficiencies. 404 Oct 42

Anatomical and behavioral characterizations of neural transplants, whether within (allograft) or across (xenograft) species, have provided evidence that the transplant survives, integrates with the host tissue, and may lead to functional recovery. Several animal models of neurodegenerative disorders demonstrate the feasibility of using neural transplantation as an alternative treatment for these human diseases. While more elaborate basic animal studies are needed, clinical trials have begun. Neural transplantation is currently used as an experimental treatment for Parkinson's disease and several investigators have suggested using the same treatment procedure for other neurodegenerative disorders, such as Huntington's and Alzheimer's disease.
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PMID:Recent advances in neural transplantation. Relevance to neurodegenerative disorders. 779 75

Apolipoprotein E (APOE, gene; ApoE, protein) is the major genetic susceptibility locus for the common forms of Alzheimer's disease (AD). There are three common polymorphisms in the population: epsilon 2, epsilon 3, and epsilon 4. The inheritance of each dose of epsilon 4 increases the risk and lowers the age of onset distribution for AD; epsilon 2 lowers the risk and increases the age of onset distribution. APOE-epsilon 4 has a high positive predictive value for AD, and is clinically useful as an adjunct in the early diagnosis of cognitively impaired patients. The APOE alleles have also been associated with risk of AD with head injury, intraneuronal localization of ApoE in animal stroke models, recovery of function after intracerebral hemorrhage, and recovery of psychological parameters after general cardiac anesthesia. A multifunctional role of ApoE in the brain implicates isoform-specific differences in interactions with several brain proteins including A beta, tau, and MAP-2. Intraneuronal ApoE is increased temporally and in relevant neurons in AD as a function of APOE genotype. Decreased glucose metabolism can be demonstrated by PET imaging in subjects two decades before the median age of onset as a function of APOE genotype. ApoE isoforms may also have different effects as antioxidants. The risk of stroke and vascular dementia has not been confirmed in neuropathological series to be related to specific APOE genotypes.
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PMID:ApoE, Alzheimer's disease, and recovery from brain stress. 932 91

The aim of Programme 38 of the Swiss National Research Foundation is to enhance collaboration between basic science and clinical application, as related to diseases of the nervous system, over a 5-year period. The 15 ongoing projects are described. They are mainly concerned with mechanisms of pathogenesis and recovery of function, and ways of modifying them therapeutically after traumatic lesions or various diseases of the nervous system such as stroke, Parkinson's disease, Alzheimer's dementia, depression, meningitis, HMSN etc.
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PMID:[National Research Program NFP 38: "Diseases of the nervous system"]. 964 54


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