Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In view of numerous studies demonstrating that intracerebral implants of fetal neural tissue can promote functional recovery and structural repair in the damaged brain, the present study examined the potential use of neocortical transplantation in newborn rats that sustained hypoxic-ischemic brain injury. Ischemic insult was induced in Long-Evans, black-hooded 1-week-old rats by unilateral common carotid artery occlusion followed by 2.5 h of hypoxia in 8% O2. One week later, animals received neocortical block transplants. At 2-6 weeks posttransplantation, animals were sacrificed and their brains examined histologically. Transplants survived in over 80% of the animals and the presence of acetylcholinesterase-positive fibers crossing the host-transplant interface provided evidence of transplant integration with the host brain. However, morphometric measurements revealed that the transplants were unable to reduce the hypoxia-ischemia-induced degeneration in the host hippocampus, caudate-putamen, or thalamus. Nonetheless the demonstrated survival of grafts in the neonatal hypoxia-ischemia model suggests a potential therapeutic effect.
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PMID:Use of fetal cortical grafts in hypoxic-ischemic brain injury in neonatal rats. 856 4

Enhancing the availability of endogenous acetylcholine by inhibition of cholinesterase with physostigmine, eptastigmine or soman at sub-toxic doses increases cerebral blood flow (CBF) and the response of this variable to changes in PaCO2. These effects are not correlated with metabolic activation, suggesting that the function of the cholinergic vasodilation is not merely to supply metabolic substrates. Since choline (Ch) can exchange between blood and the brain extracellular milieu the stage is set for possible feedback interactions between ACh synthesis and CBF. A negative feedback of CBF on ACh synthesis under conditions of a negative arteriovenous (A-V) difference for Ch across cerebral capillaries may contribute to stabilize GBF in ischemia. Eptastigmine and physostigmine significantly improve perfusion in experimental models of focal cerebral ischemia and traumatic brain injury respectively. During the short periods of time in which the A-V difference for Ch across the brain is positive, a positive feedback between cerebral free Ch and CBF may enhance the ability of the brain to recover Ch from the circulation for synthesis of membrane phospholipids. A loss of cholinergic cerebrovascular control may thus impair the survival of all cells within the CNS and contribute to the pathophysiology of dementia. Perhaps the view that the loss of cholinergic cells is the end point of Alzheimer's dementia could be modified to state that a cholinergic deficit may be the starting point of a decline in cerebral phospholipid turnover and cell membrane renewal that could lead to a generalized deterioration of cerebral function.
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PMID:Cholinergic control of cerebral blood flow in stroke, trauma and aging. 863 31

The ability of central cholinesterase inhibition to improve cerebral blood flow in the ischemic brain was tested in Sprague-Dawley rats with tandem occlusion of left middle cerebral and common carotid arteries. Cerebral blood flow was measured with lodo- 14C-antipyrine autoradiography in 170 regions of cerebral cortex. The regional distribution of blood flow was characterized in normal animals by cerebral blood flow maxima in the temporal regions. After 2 h ischemia, minimum cerebral blood flow values were found in the lateral frontal and parietal areas on the left hemisphere, and a new maximum was found in the right hemisphere in an area approximately symmetrical to the ischemic focus. Heptyl-physostigmine (eptastigmine), a carbamate cholinesterase inhibitor with prolonged time of action improved cerebral blood flow in most regions, with the exception of the ischemic core. The drug also enhanced the ischemia-induced rostral shift of cerebral blood flow maxima in the right hemisphere. The effects of eptastigmine were more marked 24 h after ischemia. Discriminant analysis showed that data from only 22 regions was sufficient to achieve 100% accuracy in classifying all cases into the various experimental conditions. The redistribution of cerebral blood flow to the sensorimotor area of the right hemisphere of animals with cerebral ischemia, a phenomenon possibly related to recovery of function, was also enhanced by eptastigmine.
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PMID:Cholinesterase inhibition improves blood flow in the ischemic cerebral cortex. 897 35

The present study was undertaken to elucidate the pathological changes in learning and memory functions and in the metabolism of cortical cholinergic neurons following microsphere embolism in the rat. Microspheres (48 microm) were injected into the right internal carotid artery of rats. Learning and memory functions were measured 7 or more days after the embolism by active and passive avoidance, and water maze tasks. In the biochemical study, cortical acetylcholine and choline contents, and choline acetyltransferase activity were measured. Cortical acetylcholinesterase-containing fibers were quantitatively estimated in the embolized rat. The active and passive avoidance, and water maze tasks were impaired in the microsphere-embolized rat. In the histochemical study, the density of cortical acetylcholinesterase-containing fibers of the ipsilateral hemisphere of the microsphere-embolized rat was decreased, but cell density was unchanged. Furthermore, microsphere embolism decreased the cortical acetylcholine concentration and choline acetyltransferase activity and increased the choline concentration. The results suggest that microsphere embolism causes severe damage to cortical cholinergic neurons, which may be, at least in part, related to the impairment of learning and memory functions in the sustained brain ischemia.
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PMID:Failure in learning task and loss of cortical cholingergic fibers in microsphere-embolized rats. 916 17

Focal ischemic brain damage and diffuse brain swelling occur in severe cases of traumatic head injury. Ischemia decreases brain acetylcholine (ACh) levels and head trauma upregulates acetylcholinesterase (AChE) in experimental animal models. The present study determined whether a brain-selective AChE inhibitor, ENA713, given once, up to 2 h after closed head injury (CHI) could reduce the vasogenic edema and accelerate recovery from neurological deficits induced by the injury in rats. ENA713 1-5 mg/kg produced a dose-related inhibition of AChE ranging from 40-85% in the cortex and hippocampus. Doses of 1, 2 and 5 mg/kg, significantly reduced the motor and neurological deficits and speeded recovery, as indicated by measurements made 7 and 14 days after injury. The two larger doses were still effective when injected 1 or 2 h after CHI. The acceleration by ENA713 of recovery of motor function was independent of its reduction in body temperature and was prevented by the simultaneous injection of mecamylamine (2.5 mg/kg), but not by scopolamine (0.2 or 1 mg/kg). Edema in the contused hemisphere (24 h after injury) and disruption of the blood brain barrier (4 h after injury) were significantly reduced (about 50%) by doses of 2 and 5 mg/kg, but not by 1 mg/kg. The data support the hypothesis that ENA713 exerts a neuroprotective effect in brain injury by preventing the decrease in cholinergic activity in cerebral vessels and in neurones.
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PMID:Cerebro-protective effects of ENA713, a novel acetylcholinesterase inhibitor, in closed head injury in the rat. 951 37

The septo-hippocampal pathway contains a major gamma-aminobutyric acid (GABA) projection to dendritic fields within the hippocampus. To determine the importance of the septo-hippocampal pathway in ischemia-induced accumulation of GABA and subsequent cell death in area CA1 of hippocampus, septo-hippocampal deafferentation of adult gerbils was performed. Electrolytic lesions were produced in the medial or medial plus lateral septal regions in gerbils 7 days prior to being subjected to 5 min forebrain ischemia. The extent of deafferentation of the dorsal hippocampus was determined histochemically by acetylcholinesterase staining. Both the medial and medial plus lateral septal lesions produced nearly complete loss of acetylcholinesterase staining in the dorsal hippocampus indicating relatively complete deafferentation. During and following ischemia, in vivo microdialysis was used to measure extracellular GABA accumulation, which reached concentrations up to 1060 +/- 143% of basal. Septo-hippocampal deafferentation in both groups of lesioned animals failed to prevent the accumulation of GABA (and glutamate) induced by ischemia, indicating that ischemia-induced GABA accumulation in area CA1 arises principally from intrinsic GABAergic interneurons. Ischemic animals with medial septal lesions did not demonstrate neuroprotection or increased damage in the stratum pyramidale 7 days after reperfusion. Since the septo-hippocampal pathway provides the source of GABAergic disinhibition within the hippocampus, neither disinhibition nor the septo-hippocampal input appear to play an important role in the development of ischemia-induced neuronal death in the hippocampus.
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PMID:Ischemic injury and extracellular amino acid accumulation in hippocampal area CA1 are not dependent upon an intact septo-hippocampal pathway. 951 50

The neurotoxicity of epsilon-toxin, one of the major lethal toxins produced by Clostridium perfringens type B, was studied by histological examination of the rat brain. When the toxin was injected intravenously at a lethal dose (100 ng/kg), neuronal damage was observed in many areas of the brain. Injection of the toxin at a sublethal dose (50 ng/kg) caused neuronal damage predominantly in the hippocampus: pyramidal cells in the hippocampus showed marked shrinkage and karyopyknosis, or so-called dark cells. The dark cells lost the immunoreactivity to microtubule-associated protein-2, a postsynaptic somal and dendric marker, while acetylcholinesterase-positive fibers were not affected. Timm's zinc staining revealed that zinc ions were depleted in the mossy layers of the CA3 subfield containing glutamate as a synaptic transmitter. The cerebral blood flow in the hippocampus was not altered significantly before or after administration of the toxin, as measured by laser-Doppler flowmetry, excluding the possibility that the observed histological change was due to a secondary effect of ischemia in the hippocampus. Prior injection of either a glutamate release inhibitor or a glutamate receptor antagonist protected the hippocampus from the neuronal damage caused by epsilon-toxin. These results suggest that epsilon-toxin acts on the glutamatergic system and evokes excessive release of glutamate, leading to neuronal damage.
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PMID:Neurotoxicity of Clostridium perfringens epsilon-toxin for the rat hippocampus via the glutamatergic system. 959 8

Various animal models, involving different brain insults, lead to memory deficits, which can be measured using behavioral tests. In numerous studies, using five different experimental models in rats, we have found that cognitive dysfunction is invariably accompanied by hippocampal CA1 and CA3 pyramidal cells degeneration. However, of these two, the most affected area changes from one model to the other. The present manuscript describes and compares the morphological alterations within the hippocampus in the following experimental models: normal aging, hypoxia, prolonged corticosterone administration, brain ischemia and cholinesterase (ChE) inhibition. In all the above, many hippocampal neurons were severely damaged, however, CA3 pyramidal cells were mostly affected in normal aging and following hypobaric hypoxia, whereas CA1 cells were especially affected following corticosterone administration, global ischemia and ChE inhibition. Several mechanisms, which might be involved in the diverse courses of the lesions are being considered: cerebral oxygen and glucose, glutamate neurotoxicity and calcium involvement. It is anticipated that elucidation of the specific role of CA1 and CA3 hippocampal sub-fields in the various experimental models might help in understanding processes such as age-related neuronal degeneration and assist in their prevention.
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PMID:Sub-regional hippocampal vulnerability in various animal models leading to cognitive dysfunction. 986 31

This study shows the effect of transient global cerebral ischemia (ISC) on hippocampal acetylcholinesterase (AChE) activity. Naive adult Wistar rats received either a brief (2 min) or a long (10 min) ischemic episode by the four-vessel occlusion method. Pre-conditioned rats received double ischemia: a 10 min episode inflicted 24 h after a 2 min event, a condition known to confer cytoprotection to CA1 pyramidal cells of hippocampus. 2 min of ischemia caused an increase in acetylcholinesterase activity both immediately and 30 min after the episode, however enzyme activity was significantly decreased after 24 h of reperfusion. 10 min of ischemia caused an increase in activity both 60 min and 24 h after ischemia. Conversely, pre-conditioned rats displayed lower activity both immediately and 60 min after ischemia. Our results suggest that: a) neuronal death, that follows 10 min of ischemia, is associated to a late increase in acetylcholinesterase activity; b) pre-conditioning is related to diminished acetylcholinesterase activity. This is in agreement with previous evidence that acetylcholinesterase inhibition and maintenance of acetylcholine levels are beneficial for cell surviving after cerebral ischemia.
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PMID:Pre-conditioning to global cerebral ischemia changes hippocampal acetylcholinesterase in the rat. 1020 84

The effect of transient cerebral ischemia on acetylcholinesterase (AChE) synthesis was studied in rats by a modified pharmacohistochemical method. The procedure involved in vivo irreversible inhibition of AChE by administration of the inhibitor diisopropyl fluorophosphate (DFP; 1.2 mg/kg b.w., i.m.) 1 h before 30 min forebrain ischemia (the four-vessel occlusion model). At the onset of ischemia, 70-75% of AChE was inhibited in the brain. Recirculation was followed by histochemical and biochemical investigations of newly synthesized AChE in the striatum, septum, cortex and hippocampus. Control sham-operated animals were treated with the same dose of DFP. For correlation, rats not treated with DFP were subjected to the same ischemic procedures and investigated simultaneously. In these rats, significant decrease in AChE activity was found in the striatum, septum and hippocampus during 24 h recirculation. In DFP treated rats, ischemia markedly depressed resynthesis of AChE; after 4 h recirculation, AChE activity was decreased by 45-60% in all investigated areas in comparison with controls and the AChE histochemistry showed only slightly stained neurons in the striatum and septum. Twenty-four hours after ischemia, these neurons were densely stained and the increase in AChE activity indicated a partial recovery of the enzyme synthesis. These results suggest that the depression of AChE synthesis after forebrain ischemia is probably transient, not accompanied by cholinergic neuron degeneration.
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PMID:Depression of acetylcholinesterase synthesis following transient cerebral ischemia in rat: pharmacohistochemical and biochemical investigation. 1037 21


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