Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined changes in the tyrosine hydroxylase (TH)-immunoreactive fibers following 5 min of cerebral ischemia in gerbils using an immunohistochemical method 1, 3 and 30 days after ischemia. Almost all CA-1 pyramidal neurons were lost 3 days after ischemia, whereas noradrenergic fibers were maintained 30 days after ischemia. The present study demonstrated that TH-immunoreactive fibers and cells were resistant to transient ischemia, and that there was no sprouting or hyperactivity in noradrenergic systems after ischemia.
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PMID:Resistance of hippocampal CA-1 noradrenergic fibers to five minutes of transient cerebral ischemia in the gerbil. 136 Oct 91

To evaluate the development of striatal ischemic cell damage in relation to alterations in dopamine (DA) transmission, one year old male Wistar rats underwent a 15 min incomplete cerebral ischemia (ICI) induced by occlusion of the common carotid arteries and by hypovolemic hypotension. The animals were divided into the following experimental groups: sham operated rats, rats with ICI without reperfusion, and rats with ICI followed by 60 min, 24 h, 72 h and 144 h of recirculation. The ischemia induced striatal lesions were investigated in serial coronal brain sections, stained with cresylviolet or immunostained for dopamine and cAMP regulated phosphoprotein (DARPP-32), for tyrosine hydroxylase (TH) and for glial fibrillary acidic protein (GFAP) immunoreactivities (IR). Measurements of striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels were made on analogous experimental groups using HPLC methods. Signs of degeneration in small to medium sized neurons were already seen after 60 min of postischemic reperfusion together with slight decreases of DARPP-32 IR and increases of GFAP IR. The damage continued to increase up to 144 h, and after 24 h of recirculation there were clearly defined areas of reduced DARPP-32 IR, overlapping with increased TH IR and increased GFAP IR. The levels of DA, DOPAC and HVA increased sharply after 60 min (151%, 462% and 201%, respectively) remained high after 24 h and normalized after 72 h of recirculation. The DA metabolism was high after 60 min and had already normalized after 24 h of recirculation. The increased DA metabolism in striatal nerve terminals in response to ischemic injury may reflect an early degenerative change in the DA terminals. The long-lasting increase in TH IR may to some extent represent an adaptive change in response to the disappearance of DA receptor-containing nerve cells. Based on the present findings it is possible that an increased D1 transmission in neostriatum immediately following the ischemic injury may contribute to striatal nerve cell degeneration in which an enhancement of NMDA receptor transduction may be implicated.
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PMID:Changes in striatal dopamine neurohistochemistry and biochemistry after incomplete transient cerebral ischemia in the rat. 166 38

The mechanisms underlying the response of the brain to ischemia are not fully understood. Biochemical and morphological changes following neocortical infarction can be investigated in rats using a model of focal cerebral ischemia induced by unilateral occlusion of the middle cerebral artery (MCA). Evaluation of ischemic damage often employs conventional histologic stains. Immunocytochemistry can be used as a valuable tool in this model to define changes in specific proteins of interest. In this study, an antiserum raised against insulin-like growth factor II (IGF-II) receptor was used to evaluate changes of IGF-II receptor immunoreactivity in the cerebral cortex of rats 4 and 7 days following permanent MCA occlusion. IGF-II receptor immunoreactivity was found to be associated with neocortical pyramidal neurons within the core of the ischemic infarct itself. The staining intensity was markedly elevated above that observed in nonischemic neurons. Immunopositive neurons exhibited a punctate staining pattern. These neurons appeared to correspond to argentophilic neurons, as defined by modified Bielschowsky silver staining. Evaluation of other neuronal markers revealed the absence of immunoreactivity for neuron-specific enolase and for tyrosine hydroxylase within the ischemic area. These observations show an increase in a specific growth factor receptor within neurons in the ischemic core of a focal infarct several days following permanent focal infarction, a time when neurons are presumed to be dead. The significance and the potential role of IGF-II receptor in lesion-induced plasticity are discussed.
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PMID:Increase in insulin-like growth factor II receptor within ischemic neurons following focal cerebral infarction. 759 34

Time-dependent changes in the tissue concentration of tyrosine hydroxylase (TH), adrenaline (A), noradrenaline (NA), and neuropeptide Y (NPY) in the early stages of cerebral ischemia were studied immunohistochemically in the amygdaloid complex of rats subjected to 1 h cerebral ischemia. Immunoreactivity to TH on the lesioned side reached a nadir at 12 h after cerebral ischemia, then gradually increased over 24 h to normal reactivity, but TH immunoreactivity between the ischemic side and the contralateral side was no different for up to 12 h after ischemia. The blood concentrations of NA and A were elevated to about twice the control concentration 12 h after ischemia, then gradually decreased back to normal. NPY immunoreactivity of both sides did not change for up to 6 h after ischemia, but NPY immunoreactivity on the lesioned side decreased over 12 h and maintained a plateau. These findings suggest that responses to cerebral ischemia between catecholamines and peptides are varied.
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PMID:Time-dependent changes of vasoactive substances in rat cerebral ischemia. 792 96

We assessed the chronological change of the expression of synaptophysin, an integral glycoprotein on the presynaptic vesicles, after a transient cerebral ischemic insult in the rat. The ischemic lesion was consistently localized in the dorsolateral part of the striatum, which was clearly visualized by a depletion of calcineurin immunostaining or increases of immunoreactivities for glial fibrillary acidic protein and tyrosine hydroxylase. Immunoreactivity for synaptophysin was transiently increased in the ischemic lesions from 3 to 7 days after cerebral ischemia. Thereafter, synaptophysin immunostaining in the damaged areas gradually decreased and finally almost disappeared one month after surgery. Because synaptophysin is located in the presynaptic vesicle, and thought to be involved in presynaptic functions such as vesicle-membrane fusion and release of neurotransmitters, present findings suggest that loss of the postsynaptic site after ischemic insult induces a transient increase of the presynaptic functions, followed by a decrease of functional presynaptic activity or trans-synaptic retrograde degeneration of axon terminals.
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PMID:Changes of immunoreactivity for synaptophysin ('protein p38') following a transient cerebral ischemia in the rat striatum. 810 40

We have developed a stroke model involving middle cerebral artery occlusion in the rat which elicits changes in cardiac and autonomic variables that are similar to those observed clinically. It is likely that these neurogenic autonomic responses are mediated by changes in neurotransmitter systems subsequent to the stroke. This possibility was investigated by examining changes in immunohistochemical staining for tyrosine hydroxylase, neuropeptide Y, leu-enkephalin, neurotoxins and dynorphin following middle cerebral artery occlusion in the rat. Computerized image analysis was used to provide semi-quantitative measurements of the changes. The ischemic region was centered primarily in the insular cortex. The results indicate that there are significant increases in immunostaining for tyrosine hydroxylase and neuropeptide Y in the insular cortex within the peri-infarct region. Neuropeptide Y staining was also significantly increased in the basolateral nucleus of the amygdala, ipsilateral to the middle cerebral artery occlusion, which did not appear to be included in the infarct. Leu-enkephalin, neurotensin and dynorphin staining was significantly elevated in the central nucleus of the amygdala ipsilateral to the occlusion of the middle cerebral artery. These neurochemical changes are discussed as possible mechanisms mediating the cardiac and autonomic consequences of stroke or as part of a process to provide neuro-protection following focal cerebral ischemia.
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PMID:Neurochemical changes following occlusion of the middle cerebral artery in rats. 854 80

Dopaminergic neurons of the substantia nigra pars compacta were examined in the rat brain following striatal infarction subsequent to transient focal cerebral ischemia. Rats had the middle cerebral artery occluded for 2 h or were sham-operated, and tyrosine hydroxylase immunoreactivity was evaluated by Western blot and immunohistochemistry at different times ranging from 1 to 60 days after ischemia. The number of tyrosine hydroxylase-immunoreactive cells in the substantia nigra pars compacta was counted under the light microscope and compared to that in the contralateral side and controls. No changes of tyrosine hydroxylase immunoreactivity were detected in the ipsilateral versus the contralateral substantia nigra of sham-operated rats or 1 day after ischemia. However, a statistically significant reduction of tyrosine hydroxylase-immunoreactive cells became apparent in the ipsilateral compared with the contralateral substantia nigra at 7 and 14 days after ischemia. This reduction showed a clear recovery at 30 days after ischemia, and no signs of difference between the ipsilateral and the contralateral side were apparent by 60 days. Therefore, the reduction of tyrosine hydroxylase immunoreactivity in the ipsilateral substantia nigra was only transiently seen from 1 to 2 weeks following ischemia. The observed loss of tyrosine hydroxylase was not accompanied by signs of cell death or gliosis in the ipsilateral pars compacta. The present results show a transitory reduction of tyrosine hydroxylase immunoreactivity in the ipsilateral substantia nigra pars compacta after focal ischemia and suggest that striatal infarction causes a transient deficit of dopaminergic function.
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PMID:Striatal infarction in the rat causes a transient reduction of tyrosine hydroxylase immunoreactivity in the ipsilateral substantia nigra. 944 Jan 26

The role of c-Fos in neurodegeneration or neuroprotection after cerebral ischemia is controversial. To investigate whether early c-Fos induction after ischemia is associated with neuroprotection, rats were subjected to 10 minutes of transient forebrain ischemia and c-Fos expression was examined. Resistant dentate granule cells and neurons in CA2-4 displayed more robust immunoreactivity than vulnerable neurons in the CA1 region of hippocampus during early hours of reperfusion. By 6 hours after reperfusion, c-Fos immunoreactivity was greatly diminished in all areas of the hippocampus. Administration of N-acetyl-O-methyldopamine (NAMDA), a compound previously shown to protect CA1 neurons against ischemia, increased c-Fos immunoreactivity in the CA1 vulnerable region at 6 hours after ischemia and protected SK-N-BE(2)C neurons from oxygen glucose deprivation. Further in vitro study showed that NAMDA potentiated phorbol-12 myristate-13 acetate (PMA)-induced c-Fos expression, AP1 binding activity, and late gene expression determined by chloramphenicol acetyltransferase (CAT) activity from AP1 containing tyrosine hydroxylase promoter-CAT fusion gene in SK-N-BE(2)C neurons. In vivo and in vitro results showed that a neuroprotectant, NAMDA, in concert with another stimulus (for example, ischemia or PMA) up-regulates c-Fos expression and suggested that the early rise of NAMDA-induced c-Fos expression in vulnerable CA1 neurons may account for neuroprotection by means of up-regulating late gene expression for survival.
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PMID:Early c-Fos induction after cerebral ischemia: a possible neuroprotective role. 1133 65

Cytidine-5'-diphosphocholine (citicoline or CDP-choline), an intermediate in the biosynthesis of phosphatidylcholine (PtdCho), has shown beneficial effects in a number of CNS injury models and pathological conditions of the brain. Citicoline improved the outcome in several phase-III clinical trials of stroke, but provided inconclusive results in recent clinical trials. The therapeutic action of citicoline is thought to be caused by stimulation of PtdCho synthesis in the injured brain, although the experimental evidence for this is limited. This review attempts to shed some light on the properties of citicoline that are responsible for its effectiveness. Our studies in transient cerebral ischemia suggest that citicoline might enhance reconstruction (synthesis) of PtdCho and sphingomyelin, but could act by inhibiting the destructive processes (activation of phospholipases). Citicoline neuroprotection may include: (i) preserving cardiolipin (an exclusive inner mitochondrial membrane component) and sphingomyelin; (ii) preserving the arachidonic acid content of PtdCho and phosphatidylethanolamine; (iii) partially restoring PtdCho levels; (iv) stimulating glutathione synthesis and glutathione reductase activity; (v) attenuating lipid peroxidation; and (vi) restoring Na(+)/K(+)-ATPase activity. These observed effects of citicoline could be explained by the attenuation of phospholipase A(2) activation. Based on these findings, a singular unifying mechanism has been hypothesized. Citicoline also provides choline for synthesis of neurotransmitter acetylcholine, stimulation of tyrosine hydroxylase activity and dopamine release.
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PMID:Citicoline: neuroprotective mechanisms in cerebral ischemia. 1179 39

Due to the development of molecular biology techniques, several types of neurotransmitter or neurotrophic factor secreting cell line can be established. These cell lines were grafted into the brain of animal models of Parkinson's disease and cerebral ischemia after encapsulating into the hollow fiber consisted of semipermeable membrane. Immunological reaction and tumor formation were prevented and functional effects were observed histologically, chemically and behaviorally. Current issues regarding encapsulated cell grafting are: delivery of neurotransmitter and neurotrophic factor simultaneously from one capsule, usage of human-derived cell lines and control of secretion from outside. There are two possible approaches regarding the usage of patient's own neural stem cells for regenerative therapy. Neural stem cells are collected from the subventricular zone of the lateral ventricle and these cells are differentiated into dopaminergic neurons using tyrosine hydroxylase induction cocktail (TH cocktail). Then, these neurons are grafted into the striatum of the patient. Another method is to inject TH cocktail into the patient's striatum in order to induce differentiation of dopaminergic neurons from the neural stem cells in vivo.
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PMID:[Intracerebral grafting of cell line or patient-derived neural stem cells for the treatment of neurological disorders]. 1278 89


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