Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of Y-8894 on experimental amnesia in rats induced by transient cerebral ischemia (600 sec) according to the method of Pulsinelli and Brierley were studied using the one trial passive avoidance response and the pole climbing discrete avoidance response. All drugs were administered to the rats immediately after recirculation. The following results were obtained: 1) In the one trial passive avoidance response test, Y-8894 (2.5, 5 and 10 mg/kg, i.p.) improved significantly the decreased latency induced by the ischemia, and it was most effective at 5 mg/kg. Calcium-hopantenate (100, 250 and 500 mg/kg, i.p.) and dihydroergotoxine (5 and 10 mg/kg, i.p.) tended to increase the latency. On the other hand, physostigmine (0.025, 0.05 and 0.1 mg/kg, i.p.), a cholinesterase inhibitor, increased the latency significantly, and it was most effective at 0.05 mg/kg. 2) The pole climbing discrete avoidance response was significantly decreased by the ischemia compared with the sham operated group, and Y-8894 (5 mg/kg, i.p.) tended to improve this decreased avoidance response. 3) Y-8894 (5 mg/kg, i.p.) facilitated recovery from the changes in glycolytic metabolism, and inhibited the accumulation of choline due to the dysfunction of the neuronal membranes induced by the ischemia. These results show that Y-8894 has beneficial effects on experimental amnesia induced by transient cerebral ischemia.
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PMID:[Pharmacological studies on Y-8894. (VII). Effects on transient cerebral ischemia-induced amnesia in rats]. 344 14

The effects of pre-treatment with ENA-713, an acetylcholinesterase (AChE) inhibitor, on changes in pre- and postsynaptic cholinergic indices in gerbil brain following transient ischemia were studied at 4 and 14 days after recirculation. In the ischemic group, hippocampal acetylcholine (ACh) level was significantly reduced (to 23% of sham-operated controls) at 4 days post-ischemia, but this reduction was completely prevented by ENA-713 treatment. Choline acetyltransferase (ChAT) and cholinesterase (ChE) activities were not significantly changed at 4 and 14 days post-ischemia. Although the maximum number (Bmax) of muscarinic ACh receptor (mACh-R) binding in the hippocampus was decreased (to 44%) without any change in affinity at 14 days post-ischemia, this decrease was also inhibited by ENA-713 treatment. In addition, histological experiment indicated that ENA-713 inhibited ischemia-induced pyramidal cell loss in the hippocampal CA1 regions. Thus, these findings suggest that ENA-713 has protective, neurotrophic and therapeutic effects on cerebrovascular type dementia due to cerebral ischemia.
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PMID:Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia. 818 20

Using a three-panel runway task, the effects of NIK-247 on impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia were investigated in rats; these effects were compared with those of the well-known cholinesterase inhibitors, tetrahydroaminoacridine (THA) and physostigmine. Intraperitoneal injection of scopolamine (0.56 mg/kg) significantly increased the number of errors (pushes made on the two incorrect panels of the three-panel gates located at four choice points). NIK-247 (3.2-18 mg/kg PO), THA (1-10 mg/kg PO), and physostigmine (0.1 and 0.32 mg/kg IP) dose-dependently reduced the increase in errors induced by scopolamine. NIK-247 (32 mg/kg) was also effective in reducing the increase in errors produced by lesions of the dorsal hippocampus. A 5-min period of cerebral ischemia markedly increased the number of errors. NIK-247 (3.2 and 10 mg/kg), given immediately after blood flow recirculation and again 20 min before the runway test carried out 24 h after ischemia, significantly reduced the increase in errors expected to occur after ischemia. Tetrahydroaminoacridine (3.2 mg/kg) and physostigmine (0.1 mg/kg) similarly reversed the increased errors in ischemic rats. These results suggest that NIK-247 alleviates the impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia, possibly through activation of the central cholinergic system.
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PMID:Ameliorative effects of the centrally active cholinesterase inhibitor, NIK-247, on impairment of working memory in rats. 843 69

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

Treatments for the symptomatic relief of Alzheimer's disease are available but despite advances in our ability to treat persons with various forms of dementia, more effective treatments are needed. The cholinesterase inhibitors donepezil, rivastigmine, and galantamine have demonstrated efficacy in improving cognition and global status and to a lesser extent, behavioral abnormalities relative to placebo in patients with mild-to-moderate Alzheimer's disease. Rivastigmine has been shown to benefit patients with dementia with Lewy Bodies and with dementia associated with Parkinson's disease. Donepezil and galantamine have also been shown to be mildly effective in dementia due to cerebral ischemia. Memantine has a distinct mechanism of action and is effective in moderate-to-severe AD. The benefits from these drugs, however, are limited and their long-term effectiveness has not been well-demonstrated. Their clinical utility is controversial. Many novel approaches that promise to provide more effective treatments are currently being pursued.
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PMID:Current and emerging pharmacological treatment options for dementia. 1672 Sep 56

The biochemical changes such as the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were investigated in rats with global cerebral ischemia and in vascular dementia (VaD) subjects in this study. The AChE activity showed a significant decrease in plasma and a significant increase in the hippocampus but not in the cerebral cortices in the post-ischemic rats as compared to the controls. The learning abilities and spatial memory were impaired in the post-ischemic rats as compared to controls. Furthermore, the AChE activity in plasma was significantly reduced in VaD subjects as compared to normal control subjects. The BuChE activity did not show any change in both post-ischemic rats and VaD patients. Interestingly, the decreased AChE activity in plasma from the post-ischemic rats and the VaD subjects showed a significant correlation with the declined learning and memory ability, and the Mini-Mental State Examination score, respectively. These data suggest that the AChE activity is involved in the cognitive recovery after ischemia, and the plasma level of AChE might be a reliable supplementary peripheral biomarker to evaluate the cognitive recovery degree of VaD patients.
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PMID:Correlations between cholinesterase activity and cognitive scores in post-ischemic rats and patients with vascular dementia. 2209 Jan 60

Decreased cerebral blood flow causes cognitive impairments and neuronal injury in vascular dementia. In the present study, we reported that donepezil, a cholinesterase inhibitor, improved transient global cerebral ischemia-induced spatial memory impairment in gerbils. Treatment with 5mg/kg of donepezil for 21 consecutive days following a 10-min period of ischemia significantly inhibited delayed neuronal death in the hippocampal CA1 region. In Morris water maze test, memory impairment was significantly improved by donepezil treatment. Western blot analysis showed that donepezil treatment prevented reductions in p-CaMKII and p-CREB protein levels in the hippocampus. These results suggest that donepezil attenuates the memory deficit induced by transient global cerebral ischemia and this neuroprotection may be associated with the phosphorylation of CaMKII and CERB in the hippocampus.
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PMID:Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils. 2224 Jan 4

Bis(7)-tacrine (B7T), a novel dimeric acetyl cholinesterase (AChE) inhibitor, has multiple neuroprotective activities against neuronal damage. However, its therapeutic effects in chronic cerebral ischemia remain unknown. In the present study, adult male Sprague-Dawley rats were subjected with permanent ligation of the bilateral common carotid arteries to investigate the roles of B7T on cognitive function, neuronal apoptosis and neurogenesis in the hippocampus. Results from spatial navigation test showed that chronic cerebral ischemia impaired spatial learning, B7T treatment shorten escape latency of ischemia rats as compared with saline-treated rats. Probe trial test indicated that spatial memory deficit of chronic cerebral ischemic animals was reversed by B7T treatment. Immunohistochemical results showed that B7T reduced neuronal apoptosis in the hippocampal CA1 region as compared with ischemia rats, and B7T treatment increased neurogenesis in the hippocampus. These findings suggest that B7T may exert its neuroprotective effects by inhibiting apoptosis and promoting neurogenesis in 2VO rats.
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PMID:Effect of bis(7)-tacrine on cognition in rats with chronic cerebral ischemia. 2233 Jul 49