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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute neurological injury from hypoxia-ischemia, hypoglycemia, and trauma is thought to be predominantly mediated by activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in the brain and the subsequent influx of calcium ions through receptor-operated channels. Several chronic degenerative diseases, such as Huntington's disease and the amyotrophic lateral sclerosis-Parkinsonism-dementia complex found on Guam, may share a similar pathogenesis due to a glutamate-like toxin. This laboratory recently reported that exposure to a reducing agent, such as dithiothreitol (DTT), selectively increases ionic current flow through NMDA-activated channels in several types of central neurons; conversely, oxidizing agents reverse this effect. To investigate the novel influence of redox modulation on NMDA neurotoxicity, in the present in vitro study we monitored survival of an identified central neuron, the retinal ganglion cell, approximately 24 h after a brief exposure to DTT. To determine the degree of killing specifically related to activation of the NMDA receptor, 2-amino-5-phosphonovalerate (APV, a selective NMDA antagonist) was added to sibling cultures. APV-preventable, glutamate-induced death was increased 70 +/- 9% with DTT treatment. This effect was totally blocked by the concomitant addition of an oxidizing agent, 5,5-dithiobis-2-nitrobenzoic acid (DTNB). These findings suggest that the enhanced killing following chemical reduction with DTT is mediated at the NMDA receptor site, and that the redox state of the NMDA receptor is crucial for the survival of neurons facing glutamate-related injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Redox modulation of NMDA receptor-mediated toxicity in mammalian central neurons. 197 Jan 45

A 73-year-old man was admitted complaining of violent involuntary movement in the left upper and lower extremities. He had a ten-year history of hypertension and had had a left thalamic hemorrhage 6 years before admission. On neurological examination Horner's sign in the right eye, typical hemiballism in the left extremities and right hemiparesis, which was caused by the previous left thalamic hemorrhage, were observed. CT scan and MRI revealed recent hemorrhage in the right subthalamic nucleus. Haloperidol, tiapride and diazepam were administered to ameliorate the ballism, but they had to be reduced in amount because of the development of parkinsonism. Two months after onset, when there was still moderate ballism, he suffocated due to a swallowing disturbance. After two hours' coma, consciousness returned gradually. Twenty-four hours after suffocation, the neurological examination revealed normal consciousness and no deterioration in other neurological symptoms, but the ballism had almost disappeared without medication. No change was detected in MRI findings and the blood flows in the basal ganglia before and after suffocation. It is interesting that transient hypoxia due to suffocation reduced hemiballism in this patient without neuroradiological findings of ischemia in the basal ganglia. The mechanisms of reduction of hemiballism after transient hypoxia were discussed.
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PMID:[Improvement in hemiballism after transient hypoxia in a case of subthalamic hemorrhage]. 225 25

Ischemic neuronal damage has been believed to make rapid progress in the course of a few days even in delayed selective neuronal death, to say nothing of acute brain necrosis. In the present study, however, we demonstrate for the first time a new type of ischemia-induced neuronal damage which progresses in the course of several weeks or a few months and we tentatively call this process "slowly progressive neuronal damage". We have focused on the chronological changes of neuronal damage in the dorsolateral striatum and neocortex following various durations of transient middle cerebral artery occlusion, which does not cause cerebral infarction and is clinically designated "transient ischemic attack". In the rats subjected to 15 min middle cerebral artery occlusion, the neocortex and lateral striatum were rarely damaged, whereas the small to medium-sized neurons only in the narrow area restricted to the dorsal striatum showed slowly progressive neuronal damage. Prolongation of ischemic duration to 30 min accelerated the evolution of neuronal damage in the dorsolateral striatum and also extended the distribution of neuronal damage to the neocortex, especially to layer III and more superficial layers. Further prolongation of ischemic duration to 45 min resulted in more rapid progress of selective neuronal death in those areas described above, whereas no animal escaped 60 min ischemia, without acute total tissue necrosis in the middle cerebral artery territory. Ischemia-induced slowly progressive neuronal damage may be implicated in the pathogenesis of such slowly progressive neurologic deterioration as dementia or Parkinsonism in patients with cerebral arteriosclerosis.
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PMID:Ischemia-induced slowly progressive neuronal damage in the rat brain. 225 91

Up to now the existence of "vascular parkinsonism" has been doubtful because conclusive clinicopathologic studies are lacking. The objective of the present magnetic resonance spectroscopy (MRS) study is to detect metabolic signs as a reflect of ischemic lesions which could be responsible for the clinical features of vascular parkinsonism. Proton MRS of the brain was performed in 12 patients suspected of vascular parkinsonism on clinical grounds and ischemic score, and in a control group of 15 patients with idiopathic Parkinson's disease. The MR spectra were measured in the striatum and deep white matter. MRS did not demonstrate metabolic evidence for the existence of ischemia (elevated lactate) or cell loss (decreased N-acetyl-aspartate levels) in patients suspected of vascular parkinsonism. Several explanations for our findings are discussed.
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PMID:Proton magnetic resonance spectroscopy in suspected vascular ischemic parkinsonism. 789 59

Increasing evidence supports the hypothesis that escalating levels of excitatory amino acids (EAAs) are responsible for neuronal cell death in a variety of acute neurological conditions including hypoxia/ischemia, trauma, seizures, and hypoglycemia. EAAs may also contribute to several chronic neurodegenerative diseases including Huntington's disease, parkinsonism, and acquired immunodeficiency syndrome dementia. A predominant form of neurotoxicity appears to be mediated by excessive activation of the N-methyl-D-aspartate subtype of glutamate receptor. This laboratory recently reported that memantine, an antiparkinsonian drug, is a potent N-methyl-D-aspartate antagonist capable of preventing the death of central neurons both in vitro and in vivo when given coincident to an EAA insult. In the present study, we found that 12 microM memantine prevented the death of neonatal rat retinal ganglion cells in primary culture when administered up to 4 hours after the initiation of N-methyl-D-aspartate receptor-mediated neurotoxicity.
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PMID:Delayed administration of memantine prevents N-methyl-D-aspartate receptor-mediated neurotoxicity. 809 95

Behavioral and histological studies were performed on a reversible ischemia model in rats. At 60 days after unilateral transient middle cerebral artery occlusion for 30 min, the operated rats exhibited the ipsiversive rotational behavior elicited by systemic administration of dopamine receptor agonist apomorphine in a dose-dependent manner. Histologically, the ipsilateral striatum of the rats showed a subdivisional ischemic injury, while the nigral dopaminergic neurons appeared intact. The striatal lesions having a cell type-specific injury were located in the dorsolateral portion of the rostral striatum and in the lateral portion of the caudal part of the nucleus. Thus, the transient cerebral ischemia could successfully produce selective damage of a striatal subdivision, which causes an abnormality in motor controls in response to dopamine receptor stimulation. The present data may provide a part of functional and anatomical basis for understanding the movement disorders associated with basal ganglia dysfunction (e.g., parkinsonism), which may occur in patients with cerebrovascular disorders.
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PMID:Subdivisional ischemic injury of the unilateral striatum causes apomorphine-induced rotational behavior in rats. 817 72

We studied 53 patients (64% females) with static brain lesions who developed progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor, eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in 12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each. Among the 30 patients with initial insult occurring at age 2 years or younger (Infant group), distribution of dystonia at follow-up was focal in three (10%), segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%). The mean latency between the original injury and onset of movement disorder was 25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an insult occurring between ages 6 and 17 (Childhood group), the distribution of dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%); the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in the Adult group (injury at age 25 or older), 11 developed dystonia, two developed parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The distribution of dystonia in the 11 patients at follow-up was segmental in three (27%) and unilateral in eight (73%). The mean latency of movement disorder onset in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in the Childhood or Adult groups became left-hand dominant; by comparison, nine of the 30 individuals in the Infant group became left-handed. In conclusion, brain injury at a young age is associated with a longer latency to onset of subsequent movement disorder, a greater tendency to development of generalized dystonia, and a greater probability of altered handedness. These tendencies may result from differences in age-related neuroplasticity.
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PMID:Delayed-onset progressive movement disorders after static brain lesions. 890 76

Embryonic nigral grafts can survive, reinnervate the striatum and reverse functional deficits in both experimental and clinical Parkinsonism. A major drawback is that only around 10% of the implanted dopaminergic neurons survive. The underlying mechanisms leading to this 90% cell death are not fully understood, but oxidative stress and a substantial loss of neurotrophic support are likely to be involved. Hypoxia and mechanical trauma, which are unavoidable during tissue preparation, may be a trigger for cell death. Recent studies have provided evidence that the type of cell death occurring is, to a large extent, apoptotic. Flunarizine is an antagonist of L-, T- and N-type calcium channels, which permits calcium entry into cells via a voltage-dependent mechanism. Flunarizine has been shown to protect neurons against death induced by serum deprivation, nerve growth factor deprivation, oxidative stress, axotomy and ischemia. This study was designed to investigate whether flunarizine can protect grafted embryonic dopaminergic neurons from death when implanted in a rat model of Parkinson's disease. Addition of 1 microM flunarizine inhibited cell death in a suspension of cells derived from the rat's ventral mesencephalon and when such a treated suspension was injected into the neostriatum there was a 2.6-fold greater number of surviving dopaminergic neurons, a doubling of the graft volume and a doubling of the volume of the host neostriatum innervated by dopaminergic fibers from the graft, compared with suspensions not exposed to flunarizine. Furthermore, rats injected with cells that had been exposed to flunarizine displayed a greater recovery of function in the amphetamine-induced rotation test.
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PMID:Flunarizine improves the survival of grafted dopaminergic neurons. 1061 92

Nitric oxide (NO), an intercellular messenger and a normal metabolic product, takes an active part in the regulation of physiologically significant functions of the cardiovascular, immune, and nervous systems. At the same time when produced in excess amounts, NO as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions (parkinsonism, Alzheimer's disease, Huntington's chorea). Numerous experimental data show the ambiguous effects of NO on the development of cerebral infarct. NO as an active vasodilatory and antithrombogenic agent may reduce cerebral damage in early ischemia. There is evidence for the involvement of NO in the body's adaptation to oxygen starvation and ischemic tolerance formation. In the postischemic period, NO is a major factor of neuronal necrosis and apoptosis. The currently established ideas on the processes of cerebral NO production and on the pathogenetic mechanisms of this agent's cytotoxicity open up new vistas for selective blockers of various NO synthesis enzymes (neuronal, endothelial, glial cellular, and macrophagal and neutrophilic NO synthases) used in the treatment of acute vascular abnormalities of the central nervous system.
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PMID:[The role of nitric oxide and other free radicals in ischemic brain pathology]. 1083 6

A case of parkinsonian syndrome caused by normal pressure hydrocephalus (NPH) accompanied by cauda equina neurinoma is reported. A 69-year-old woman presented with typical symptoms of parkinsonism, including akinesia, resting and postual tremor, and cog-wheel rigidity. CT scan of the brain revealed dilatation of ventricles, but she did not present dementia and urinary incontinence that are common symptoms in NPH. Her cerebrospinal fluid (CSF) pressure was normal, and her protein level was high at 2,970 mg/dl. An electroencephalogram (EEG) showed diffuse slow waves. An IMP-SPECT images of the brain showed diffuse reduction of radioisotope uptake. Levodopa was not effective in treating her parkinsonism. Removal of the tumor caused dramatic improvement in her parkinsonism. Her CSF protein level was normalized and EEG and SPECT images were improved after the operation. However, ventricular size on brain CT showed no change. It was considered that the causal mechanism of NPH was due to high protein levels in the CSF. The parkinsonism in this case was caused by dysfunction of the circuits linking the cortex, basal ganglia, and thalamus associated with metabolic disorder due to periventricular ischemia. Typical parkinsonism caused by NPH associated with spinal cord tumor has not been reported. When we examine a patient with parkinsonian syndrome caused by NPH, we should check the CSF protein level. And if that level is high, the possibility of spinal cord tumor should be considered.
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PMID:[A case of parkinsonian syndrome caused by normal pressure hydrocephalus accompanied by the cauda equina neurinoma]. 1242 62


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