Endogenously released DOPA is a causal factor for glutamate release and resultant delayed neuronal cell death by transient ischemia in rat striata

Camporesi

European Journal of Applied Physiology

et al. 2002

The usefulness of the administration of hyperbaric oxygen (HBO) in the treatment of acute focal cerebral ischemia remains debatable. A significant association exists between focal cerebral injury and an excessive release of extracellular dopamine (DA). In vivo microdialysis was used in the present study to examine the effect of HBO on DA release in the striatum during ischemia and reperfusion in rats. The histological changes occurring were also evaluated. Focal cerebral ischemia was induced by occlusion of the middle cerebral artery (MCA) using a surgically placed intraluminal filament. Control rats (n=8) were subjected to 1 h of ischemia, whilst the study rats (n=8) were in addition treated with HBO (2.8 atmospheres of absolute pressure 100% O(2)) during ischemia. Both groups were returned to breathing room air at normal pressure during reperfusion. Microdialysis samples were continuously collected at 15 min intervals at 2 microl.min(-1). The [mean (SE)] increase in release of striatal DA attained significance after 30 min of occlusion of MCA [170 (24)%], and continued to increase [268 (26)% at 45 min] reaching a peak level at 60 min [672 (59)%] before returning to the baseline level during the late reperfusion phase. There was no significant change in the level of DA in HBO treated rats during the period of ischemia. A significant reduction in edema and neuronal shrinkage were observed by histological examination in HBO treated rats when compared to the control rats. The results showed that HBO, when administered during ischemia, offered significant neuroprotection in our experimental model of transient focal cerebral ischemia in the rat. The mechanism seems to imply, at least in part, a reduced level of DA.

Section: Discussionsupporting

confidence: 89%

Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal dopamine release in a rat model of transient middle cerebral artery occlusion

Camporesi

European Journal of Applied Physiology

et al. 2002

“…It is well known, in fact, that a massive release of dopamine occurs during ischemic events in the striatum and that endogenous dopamine amplifies the neuronal damage caused by excitotoxicity and energy deprivation. [13][14][15][16] Endogenous dopamine, however, can facilitate both acute necrotic and delayed apoptotic neuronal death by additional mechanisms, such as the control of intracellular calcium levels and the production of free radicals. 43,44 The ischemia-induced abnormal release of endogenous dopamine in vulnerable brain areas, such as striatum, cerebral cortex, and hippocampus, may represent the critical factor that transforms a transient ischemic attack into an ischemic episode causing irreversible consequences for brain tissue and synaptic circuits.…”

Section: Saulle Et Al Dopamine and Postischemic Ltp 2981mentioning

confidence: 99%

“…10 -12 Ischemia also causes a large increase in dopamine levels in the striatum, 13 and considerable evidence supports the idea that monoamines or their metabolic by-products may become neurotoxic during metabolic impairment, either directly or from interplay with the glutamatergic system. 14,15 In an in vitro model of striatal ischemia, for example, reduction of dopamine release has been found to be associated with a better histological outcome, 13 and unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra has been reported to reduce the volume of striatal necrosis induced by middle cerebral artery occlusion. 16 Thus, the dopaminergic nigrostriatal pathway could be highly involved in the vulnerability of the striatum to ischemia, and glutamate-dopamine interactions may play a key role in striatal ischemic insult.…”

mentioning

confidence: 99%

Endogenous Dopamine Amplifies Ischemic Long-Term Potentiation via D1 Receptors

Saulle

Centonze

Martín

et al. 2002

Stroke

Background and Purpose-Several observations indicate that, during energy deprivation, endogenous dopamine may become neurotoxic. Accordingly, the nucleus striatum is a preferential site of silent infarcts in humans, and experimental ischemia caused by homolateral carotid occlusion selectively damages this dopamine-enriched brain area. In an attempt to clarify how dopamine takes part in ischemia-induced neuronal damage, we performed in vitro electrophysiological recordings from neurons of the nucleus striatum. Methods-Intracellular recordings with sharp microelectrodes were performed from corticostriatal slices. Slices were obtained from both rats and wild-type and dopamine D1 receptor-lacking mice. In some experiments, the striatum was unilaterally denervated by injecting the dopamine-specific neurotoxin 6-hydroxydopamine in the homolateral substantia nigra. Dopamine agonists and antagonists, as well as drugs targeting the intracellular cascade coupled to dopamine receptor stimulation, were applied at known concentrations. Results-Manipulation of the dopamine system failed to affect the membrane depolarization of striatal neurons exposed to combined oxygen and glucose deprivation of short duration, but it reduced the amplitude of postischemic long-term potentiation (LTP) expressed at corticostriatal synapses. In particular, pharmacological blockade or genetic inactivation of D1/cAMP/protein kinase A pathway prevented the long-term increase of the excitatory postsynaptic potential (EPSP) amplitude caused by a transient ischemic episode, while it failed to prevent the increase of the EPSP half-decay coupled to ischemic LTP. Conclusions-The present data suggest that endogenous dopamine, via D1 receptors, selectively facilitates the expression of ischemic LTP on the AMPA-mediated component of the EPSPs, while it does not alter the expression of this form of synaptic plasticity on the N-methyl-D-aspartate-mediated component of corticostriatal synaptic potentials. Understanding the cellular and molecular mechanisms of ischemia-triggered excitotoxicity offers hope for the development of specific treatments able to interfere with this pathological process.

“…For example, substantial increases in dopamine levels in this brain region were reported following 10 minutes of arterial occlusion, which then returned to baseline levels after 60 minutes (40). However, other studies have reported that dopamine protects neurons against glutamate-induced excitotoxicity (37) and that dopamine levels are reduced following ischemia (38)(39)(40). In addition, it has been shown that some experimental conditions can lead to increased TH levels in the striatum (21), suggesting the existence of tissue-specific modulation.…”

Section: Discussionmentioning

confidence: 97%

“…Existing data point to increased levels of dopamine during ischemia (34,35), particularly in the neostriatum (18,(36)(37)(38)(39). For example, substantial increases in dopamine levels in this brain region were reported following 10 minutes of arterial occlusion, which then returned to baseline levels after 60 minutes (40). However, other studies have reported that dopamine protects neurons against glutamate-induced excitotoxicity (37) and that dopamine levels are reduced following ischemia (38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

La atorvastatina protege las neuronas GABAérgicas y dopaminérgicas del sistema nigroestriatal en un modelo experimental de isquemia cerebral focal transitoria en ratas

et al. 2014

Author contributions:Angélica María Sabogal: conducted the experiments, collected and discussed results, and prepared the manuscript. César Augusto Arango: consulted on cerebral ischemia procedures and nigrostriatal physiology; discussed results and reviewed the manuscript. Gloria Patricia Cardona: managed and supervised experiments; reviewed scientific merit; performed input protein analysis; reviewed, revised and approved the manuscript; submitted the manuscript. Ángel Enrique Céspedes: approved the project; managed and supervised the study; analyzed and interpreted the results, discussions and conclusions; reviewed and approved the manuscript. Introduction: Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown. Objective: To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery. Materials and methods: Twenty-eight male eight-week-old Wistar rats were used in this study. Both sham and ischemic rats were treated with atorvastatin (10 mg/kg) or carboxymethylcellulose (placebo) by gavage at 6, 24, 48 and 72 hours post-reperfusion. We analyzed the immunoreactivity of glutamic acid decarboxylase and tyrosine hydroxylase in the globus pallidus, caudate putamen and substantia nigra. Results: We observed neurological damage and cell loss in the caudate putamen following ischemia. We also found an increase in tyrosine hydroxylase immunoreactivity in the medial globus pallidus and substantia nigra reticulata, as well as a decrease in glutamic acid decarboxylase immunoreactivity in the lateral globus pallidus in ischemic animals treated with a placebo. However, atorvastatin treatment was able to reverse these effects, significantly decreasing tyrosine hydroxylase levels in the medial globus pallidus and substantia nigra reticulata and significantly increasing glutamic acid decarboxylase levels in the lateral globus pallidus. Conclusion: Our data suggest that post-ischemia treatment with atorvastatin can have neuroprotective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders. Atorvastatin protectsKey words: GABAergic neurons, dopaminergic neurons, brain ischemia; models, animal; rats. doi: http://dx.doi.org/10.7705/biomedica.v34i2.1851La atorvastatina protege las neuronas gabérgicas y dopaminérgicas del sistema nigroestriatal en un modelo experimental de isquemia cerebral focal transitoria en ratas Introducción. La isquemia cerebral es la tercera causa de muerte y la primera de discapacidad permanente en el mundo. La atorvastatina es un fárm...