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)

Glutamate, aspartate, GABA, glycine and taurine levels have been measured in rat thalamus and in cerebral cortex at different time intervals (3rd, 7th, 15th, 30th day) after cerebellectomy. A decrease in glutamate, aspartate and GABA was detected at the 7th day after cerebellectomy in the thalamus and at the 15th day in the cerebral cortex; at the 30th day after cerebellectomy the levels of these amino acids in the thalamus and in the cerebral cortex were observed to have recovered to control values. No statistically significant difference in glycine and taurine levels in the thalamus and in the cerebral cortex after cerebellectomy could be seen. These results show that the functional recovery process after cerebellar injury is associated with a complex modification of amino acid levels in thalamus and in cerebral cortex.
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PMID:Neurotransmitter amino acid levels in rat thalamus and cerebral cortex after cerebellectomy. 168 98

Certain instances of neuronal degeneration secondary to brain damage might be functionally beneficial, and steps taken to protect against such degeneration may adversely affect behavioural outcome. After unilateral damage to the intrinsic neurons of the striatum, which includes GABAergic striatonigral projections, delayed trans-synaptic degeneration occurs in the ipsilateral substantia nigra pars reticulata (SNr). This degeneration was prevented by a 2-week regimen of muscimol delivered intraventricularly via osmotic minipumps. Muscimol is a direct-acting GABA agonist that presumably substituted for the absent GABA at the interface between the degenerating striatonigral GABAergic terminals and the GABAergic receptors located on SNr neurons. Sensorimotor asymmetry tests sensitive to unilateral striatal damage were carried out for 4 weeks to determine the functional consequences of the sparing of SNr neurons. Recovery of function was not improved. Instead, tactile extinction and hemiplegia were exaggerated in the contralateral forelimb. Other impairments were unaffected by the muscimol. The experiment was repeated using diazepam, rather than muscimol, to address the possibility that the disruptive effects of muscimol might reflect a more general disruptive influence on recovery processes. Diazepam, which has been shown in our lab to disrupt recovery of function after cortical lesions and to potentiate lesion-associated atrophy in remote subcortical structures, is an indirect-acting GABAergic agonist that requires GABA for its mechanism of action. Because GABAergic terminals at the SNr were destroyed, diazepam (as expected) failed to prevent SNr degeneration. Although diazepam presumably enhanced GABAergic synaptic activity in other brain regions, diazepam had no significant effect on postoperative behavioural function. Apparently, in the first experiment, the prevention of SNr degeneration per se was instrumental in the detrimental effects of muscimol. The rescued SNr neurons may have contributed to dysfunction because they lacked inhibitory GABAergic control. Transsynaptic degeneration secondary to brain damage was discussed as it might relate to release phenomena and their treatment by surgery or transmitter blocking agents in the clinical literature.
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PMID:Rescuing neurons from trans-synaptic degeneration after brain damage: helpful, harmful, or neutral in recovery of function? 216 18

A variety of putative neurotransmitters has been described in the red nucleus (RN). Measurement of neurotransmitter biochemical markers and study of their specific localizations using morphological techniques in lesion and deafferentation of the RN indicate the participation of glutamate (Glu) in corticorubral transmission and the presence of GABA in RN intrinsic neurones. The cerebellorubral projection may contain at least two populations of fibres, the one using acetylcholine and the other Glu as neurotransmitter. The presence of a serotoninergic input was also demonstrated. Selective deafferentations of the RN, particularly from its cerebellar input, result in biochemical and immunohistochemical responses indicative of increased corticorubral glutamatergic and local GABAergic transmission. These adaptive changes of neuronal transmission as well as the previously described sprouting of corticorubral nerve terminals may contribute to functional recovery after cerebellectomy in adult animals.
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PMID:Putative neurotransmitters in the red nucleus and their involvement in postlesion adaptive mechanisms. 289 48

We investigated the participation of catecholaminergic mechanisms in the functional recovery from motor cortex lesions in young (9 months) and aged (26 months) rats. The animals were studied during the recovery period from an hemiplegic syndrome secondary to small motor cortex lesions potentiated by the localized, chronic (7 days) infusion of GABA into the lesion site. Acute administration of haloperidol (0.1 mg/kg IP) to these recovered animals induced a re-emergence of the contralateral motor syndrome in both groups. In the young group, the haloperidol-induced hemiplegia lasted one day whereas in the aged animals the deficit was significantly prolonged lasting three days. Apomorphine administration (0.5 mg/kg IP) prior to or immediately after haloperidol injection failed to prevent or reverse the reappearance of the motor deficit. Adult animals recovered from motor cortex aspirations performed 7 to 12 months prior were refractory to haloperidol effects. Amphetamine administration to young rats treated chronically with saline or GABA infusion into the somatomotor region also failed to alter the clinical evolution of the motor deficit. The evidence suggests that dopaminergic mechanisms are involved in the functional recovery from brain lesions and that these mechanisms are most susceptible to neuroleptic blockade during the early post-lesional period. The deleterious effects of dopaminergic blockade are heightened in aged populations. The use of dopaminergic antagonists in brain-lesioned subjects, and particularly in geriatric populations, is considered potentially harmful, particularly in the early stages of the recovery process.
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PMID:Recovery from GABA-mediated hemiplegia in young and aged rats: effects of catecholaminergic manipulations. 368 25

We grafted fetal striatal cells in ischemic rat models, and investigated graft survival/growth, GABA release, GABAA receptor reorganization and functional recovery. One hour intraluminal occlusion of the middle cerebral artery (MCA) induced ischemic infarct in the lateral part of the striatum and adjacent cortex. In ischemic rats, the acquisition of Morris' water-maze learning was significantly slower than that of control rats. In these animals GABA level in the globus pallidus, detected by microdialysis, was about the half of that of controls. However, after the grafts of fetal striatal cells in the striatopallidum, the acquisition was improved, thus no difference was observed in the time course of learning curves in control and grafted animals. GABA level recovered to almost normal level by the graft. It further increased by the treatment of a GABA uptake blocker (nipecotic acids) in the perfusion. In the grafts, GABAA receptor organization detected by autoradiography using [3H] labeled SR95531 was restored for more than 1 year after the graft. Data suggest that fetal striatal cell grafts in infarct striatum may partially reconstruct striatopallidal GABA projection and reorganize GABAA receptor. This might be a basis of improvement of function.
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PMID:Striatal grafts in infarct striatopallidum increase GABA release, reorganize GABAA receptor and improve water-maze learning in the rat. 818 93

It has been proposed that functions associated with the prefrontal cortex could change as a consequence of aging. Previous experiments in young rats have demonstrated that anatomical lesions or chronic GABA infusions into this area produce deficits in spatial delayed alternation tasks. The present study examines the effect of chronic (7 days) GABA or saline infusion into the prefrontal cortex on the performance of delayed alternation task in old rats (24 months). The results suggested that aged rats needed more sessions to acquire the delayed alternation task. GABA infusions into the prefrontal cortex produced deficits in spatial alternation tasks similar to those previously observed in young rats. Performance rapidly recovered after the infusion period. Histological analysis showed similar lesion size in both groups. The results suggest that aged prefrontal cortex and/or related areas participating in the acquisition of the delayed alternation task are more sensitive to aging processes. Furthermore, the prefrontal cortex is important for the retention of a previously learned spatial delayed alternation task. The structures involved in functional recovery from these deficits appear to be fully functional in aged rats.
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PMID:Chronic infusions of GABA into the medial prefrontal cortex induce spatial alternation deficits in aged rats. 829 48

The use of glutamate antagonists and GABA agonists may protect neurons from the effects of transient ischemia. Felbamate is a new antiepileptic drug with glutamate antagonist and GABA agonist properties. We tested the efficacy of felbamate in a gerbil model of transient forebrain ischemia. Damage assessment was done with silver staining at 7 and 28 days after 5 min of bilateral carotid occlusion. Cerebral cortex, hippocampus (CA1 and CA4), thalamus and striatum were evaluated on a 4-point scoring system. The animals sacrificed at 28 days were also tested in a water-maze task to assess recovery of function. The initial dose of felbamate (300 mg/kg) was given 30 min before the ischemic insult in one set of animals and 30 min after the insult in another set of animals. There were 8 animals tested per group (total: 48 animals). There was significant neuronal protection with the use of felbamate, both before and after ischemia in all regions of the brain. Protection was seen in animals sacrificed at 7 and 28 days. Protection was moderate when felbamate was used before ischemia. It was highly significant when felbamate was given 30 min after the insult. Behavioral studies however did not show any difference in the felbamate treated animals versus the saline treated controls. The structural protection with felbamate was very significant when used in the post-ischemic period. This window for protection merits further evaluation in relation to the clinical setting of stroke.
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PMID:Neuroprotection with felbamate: a 7- and 28-day study in transient forebrain ischemia in gerbils. 884 83

Among the pathological processes initiated by traumatic brain injury are excessive neuroexcitation and target cell deafferentation. The current study examines the contribution of these injury components, separately as well as their combined effect, on postinjury alterations in the capacity for long-term potentiation and the immunolocalization of N-methyl-D-aspartate receptors and GABA. Adult rats underwent central fluid percussion traumatic brain injury, electrolytic bilateral entorhinal cortex lesions, or a combined injury of both procedures separated by 24 h. At two or 15 days postinjury, the capacity for long-term potentiation of the Schaffer collateral-commissural input to CA1 was measured in acute electrophysiological recordings. Entorhinal cortical lesions resulted in time-dependent increases in the effectiveness of tetanic stimulation to elevate population postsynaptic potentials and population spike amplitudes. These lesions also resulted in a marked intensification in the density of N-methyl-D-aspartate receptors in the CA1 stratum lacunosum-moleculare. All injury conditions that included fluid percussion as a component (alone or in combined injuries) produced a persistent impairment in long-term potentiation of the evoked population postsynaptic potentials. Thus, in combined injuries, the presence of concussion-induced neuroexcitation attenuated deafferentation-induced response increases. Both N-methyl-D-aspartate receptor and GABA immunobinding following combined injuries were also reduced relative to those observed following entorhinal lesions alone. The present results suggest that a process of receptor plasticity, possibly involving reactive synaptogenesis, may contribute to postdeafferentation enhancements of long-term potentiation, and that a traumatic brain insult will attenuate these enhancements. This interaction of different injury components suggests that recovery of function following brain injury may be enhanced by pharmacological reduction of neuroexcitation during postinjury intervals of reactive receptor plasticity.
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PMID:The effect of combined fluid percussion and entorhinal cortical lesions on long-term potentiation. 947 2

Intrastriatal transplantation of fetal ventral mesencephalon (VM) is currently explored as a potential clinical therapy in Parkinson's disease (PD). Although providing substantial benefit for the patient, behavioral recovery so far obtained with intrastriatal VM grafts is not complete. Using the 6-hydroxydopamine lesion model of PD, we show here that near-complete restoration of the striatal dopamine (DA) innervation can be achieved by multiple intrastriatal microtransplants of fetal DA cells; nevertheless, complete recovery in complex sensorimotor behaviors was not obtained in these animals. In line with the current model of basal ganglia function, this suggests that the lesion-induced overactivity of the basal ganglia output structures, i.e., the substantia nigra (SN) and the entopeduncular nucleus, may not be completely reversed by intrastriatal VM grafts. In the present study, we have transplanted fetal VM tissue or fetal striatal tissue, as a source of DA and GABA neurons, respectively, into the SN of DA-depleted rats. Intranigral VM grafts induced behavioral recovery in some sensorimotor behaviors (forelimb akinesia and balance tests), but the effect did not exceed the recovery observed after intrastriatal VM grafts. Intranigral grafts of striatal tissue induced a pattern of functional recovery which was distinctly different from that observed after intranigral VM grafts, and recovery in coordinated forelimb use in the paw-reaching test was even more pronounced than after intrastriatal transplantation of VM cells. Combined transplantation of DA neurons into the striatum and GABA-rich striatal neurons into the SN induced additive effects of behavioral recovery observed in the forelimb akinesia test. We propose that intranigral striatal transplants, by a GABA-mediated inhibitory action, can reduce the overactivity of the host SN projection neurons and can induce significant recovery in complex motor behavior in the rat PD model and that such grafts may be used to increase the overall functional efficacy of intrastriatal VM grafts.
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PMID:Intranigral transplants of GABA-rich striatal tissue induce behavioral recovery in the rat Parkinson model and promote the effects obtained by intrastriatal dopaminergic transplants. 1007 93

The mechanisms of recovery of manual dexterity after unilateral lesion of the sensorimotor cortex in adult primates remain a matter of debate. It has been proposed that the cortical zone adjacent to the lesion may take over part of the function of the damaged cortex. To investigate further this possibility, two adult (4-5 years old) macaque monkeys were trained to perform a natural precision-grip task to assess hand dexterity. Intracortical microstimulations (ICMS) were used to map the hand area in M1 on both hemispheres. Ibotenic acid was then injected intracortically to damage the representation in M1 of the preferred hand. Subsequent histological analysis indicated that the hand representation in M1 was indeed lesioned, but, due to a spread of ibotenic acid, the lesion encroached a significant extent of the hand representation in the primary somatosensory cortex. A few minutes after infusion of ibotenic acid, there was a complete loss of dexterity of the preferred hand, which lasted for 1-2 months. Later, a progressive functional recovery of the affected hand took place over a 3- to 4-month period, reaching a stable level corresponding to 30% of the pre-lesion behavioral score. ICMS remapping, conducted nine months after the lesion, revealed that stimulation of the intact or lesioned M1 did not induce any visible movement of the recovered hand. The M1 hand representation on the intact hemisphere was similar to that observed before the lesion. Transient inactivation of the M1 hand/arm areas or of the dorsal and ventral premotor cortical areas (PM) on both hemispheres was undertaken by using microinjections of the GABA-agonist muscimol. Inactivations of M1 had no effect. Inhibition of PM in the damaged hemisphere suppressed the recovered manual dexterity of the affected hand. These results suggest that PM plays a significant role in the incomplete functional recovery of hand dexterity following unilateral damage of the sensorimotor cortex in adult monkeys.
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PMID:Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys. 1047 53


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