Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, several systems of neuropeptides have been demonstrated to have anticonvulsant action in some forms of epilepsy to some extent. However, considerably less knowledge has been taken to their involvement in convulsive disorders either with regard to the development, expression or control of seizures. In this study, therefore, we examined the influence of amygdaloid kindling, an experimental model of temporal lobe epilepsy, on thyrotropin-releasing hormone (TRH), somatostatin (SS), cholecystokinin (CCK) and substance P (SP) content in the amygdala/piriform cortex and hippocampus. Male Sprague-Dawley rats were implanted bipolar electrodes into the left amygdala under pentobarbital anesthesia. Daily kindling stimulation was made to the left amygdala with 1 sec, 60 Hz, 400 microA, until 5 consecutive fully kindled generalized convulsive seizures were elicited. Subsequently, amygdaloid kindled rats were decapitated 30 min, 24 hrs, 48 hrs, 7 days and 21 days after the last amygdaloid stimulation, and the amygdala/piriform cortex and hippocampus were dissected. Control animals only received chronic electrodes, but no stimulation was delivered. The immunoreactivity of TRH, SS, CCK and SP was examined by methods of specific radioimmunoassay. The TRH content in these two brain regions significantly increased 24 hrs after the last kindled convulsion. This increase became maximal 48 hrs after the last convulsion: about 3-fold and 4-fold of the control in the amygdala/piriform cortex and hippocampus, respectively. Such increases in the TRH content tended to persist for 7 days, but returned to the control level 21 days after the last convulsion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Effect of amygdaloid kindling on thyrotropin-releasing hormone, somatostatin, cholecystokinin and substance P contents of the amygdala/piriform cortex and hippocampus of rats]. 246 12

It has been hypothesized on the basis of animal models of epilepsy that abnormal neural activity in epilepsy may be related to reorganized neural circuits that facilitate epileptogenesis. Little evidence of this was available for human epilepsy. This paper provides the first evidence of such reorganization of a hippocampal seizure focus in human temporal lobe epilepsy (TLE). This reorganization involves the selective loss of somatostatin and neuropeptide Y immunoreactive interneurons, and axonal sprouting of other neuropeptide Y neurons and dynorphin-A immunoreactive granule cells. This set of changes is not exactly like those that are reported in animal models.
 ...
PMID:Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy. 256 20

The effect of carbamazepine treatment on CSF-somatostatin-like immunoreactivity (SLI) in patients suffering from temporal lobe epilepsy was investigated. A baseline lumbar puncture was performed on 12 patients and 10 normal volunteers. A second tap was repeated only in patients when they were on peak of carbamazepine concentration for 10 days. Levels of CSF-SLI were measured by RIA. No significant differences were found in CSF-SLI basal concentrations between epileptics and controls, whereas a significant decrease (p less than .0002 Duncan's multiple range test) of CSF peptide levels occurred in 9 of 12 patients under medication. Although the neural mechanism through which carbamazepine lowers CSF-SLI is still unknown, the results of the present study suggest that the reported effect might be part of the apparatus by which carbamazepine exerts its anticonvulsant action.
 ...
PMID:Carbamazepine lowering effect on CSF somatostatin-like immunoreactivity in temporal lobe epileptics. 287 37

The occurrence of seizure activity in human temporal lobe epilepsy or status epilepticus is often associated with a characteristic pattern of cell loss in the hippocampus. An experimental model that replicates this pattern of damage in normal animals by electrical stimulation of the afferent pathway to the hippocampus was developed to study changes in structure and function that occur as a result of repetitive seizures. Hippocampal granule cell seizure activity caused a persistent loss of recurrent inhibition and irreversibly damaged adjacent interneurons. Immunocytochemical staining revealed unexpectedly that gamma-aminobutyric acid (GABA)-containing neurons, thought to mediate inhibition in this region and predicted to be damaged by seizures, had survived. In contrast, there was a nearly complete loss of adjacent somatostatin-containing interneurons and mossy cells that may normally activate inhibitory neurons. These results suggest that the seizure-induced loss of a basket cell-activating system, rather than a loss of inhibitory basket cells themselves, may cause disinhibition and thereby play a role in the pathophysiology and pathology of the epileptic state.
 ...
PMID:Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. 287 52

The El (epileptic) mouse is a model of hereditary sensory precipitated temporal lobe epilepsy. We compared vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI), somatostatin-like immunoreactivity (SS-LI), and gamma-aminobutyric acid-like immunoreactivity (GABA-LI) in the mid-hippocampal region of El and C57BL/6 mice. Specific interneuron populations with VIP-LI and GABA-LI were elevated in the El mice, whereas SS-LI populations were unchanged. These neurochemical alterations may be contributing to the epileptic predisposition of El mice.
 ...
PMID:VIP-, SS-, and GABA-like immunoreactivity in the mid-hippocampal region of El (epileptic) and C57BL/6 mice. 321 26

This study determined differences of fascia dentata (FD) peptide and inhibitory neuroanatomy between patients with epileptogenic hippocampal sclerosis (HS), those with extrahippocampal seizure pathologies, and autopsy comparisons. Surgically treated temporal lobe epilepsy patients were clinically classified into two pathogenic categories: (1) HS with focal mesial temporal neuroimaging and histories of initial precipitating injuries to the brain (n = 18) and (2) non-HS patients with extrahippocampal mass lesions or idiopathic seizures (i.e., without lesions or HS; mass lesion/idiopathic; n = 9). The hippocampal sections were studied for (1) granule cell, hilar, CA4, and CA3 neuron densities; (2) hilar densities and the percentage of neurons immunoreactive (IR) for neuropeptide Y (NPY), somatostatin (SS), and glutamate decarboxylase (GAD); (3) densities of GAD neurons in the lower granule cell and infragranular zone (basket-like cells); (4) the semiquantitative pattern of IR peptides/GAD FD molecular layer axon sprouting; (5) IR gray values (GV) of the FD molecular layers; and (6) the thickness of the supragranular molecular layer. Results showed the following. (1) Compared to autopsies, both HS and mass lesion/idiopathic patients showed less granule cell and CA3 neuron densities, but there were no statistical differences between the latter two pathogenic categories. (2) By contrast, compared to autopsies and mass lesion/idiopathic cases, HS patients showed less hilar and CA4 neuron densities, and there were no differences between autopsies and mass lesion/idiopathic. (3) Compared to autopsies, the NPY and SS hilar neuron densities in HS patients, but not mass lesion/idiopathic cases, were less. (4) Compared to autopsies, the hilar GAD neuron densities for HS and mass lesion/idiopathic patients were not less. (5) In HS patients the averaged percentages of hilar SS neurons were less than autopsies, and no other differences of IR hilar percentages were found. (6) The densities of GAD basket-like neurons and the thickness of the supragranular molecular layer were not different between any combination of pathogenic categories and autopsies. (7) By semiquantitative visual assessments, peptides/GAD axon sprouting into the FD was greater in HS compared to mass lesion/idiopathic or autopsies. (8) Compared to mass lesion/idiopathic cases, in HS NPY outer molecular layer GVs were lower, SS GVs were not different, and GAD inner molecular layer GVs were higher. (9) Analyses comparing the two pathogenic categories and neuron densities with peptides/GAD axon sprouting found six comparisons that correlated sprouting with hilar and CA4 neuron losses, and four comparisons showing greater sprouting in HS compared to mass lesion/idiopathic.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata. 775 60

Loss of hippocampal interneurons has been reported in patients with severe temporal lobe epilepsy and in animals treated with kainate. We investigated the relationship between KA induced epileptiform discharge and loss of interneurons in hippocampal slice cultures. Application of KA (1 microM) produced reversible epileptiform discharge without neurotoxicity. KA (5 microM), in contrast, produced irreversible epileptiform discharge and neurotoxicity, suggesting that the irreversible epileptiform discharge was required for the neuronal loss. Loss of CA3 pyramidal cells and parvalbumin-like immunoreactive (PV-I) interneurons preceded loss of somatostatin-like immunoreactive (SS-I) interneurons suggesting a different time course of KA neurotoxicity in these subpopulations of interneurons.
 ...
PMID:Hyperexcitability and cell loss in kainate-treated hippocampal slice cultures. 790 92

Intracerebral or intraperitoneal injections of kainic acid, an agonist at a class of glutamate receptors, have been extensively used to model temporal lobe epilepsy. In the present study we compared the types and distributions of selectively vulnerable neurons in the ipsi- and contralateral hippocampi following unilateral kainate injections into the CA3 subfield in order to examine whether "proximal" or "distant" neuronal damage resembled the pathology, and possibly also the mechanism, of human temporal lobe epilepsy. The degeneration of principal cells in the different hippocampal subfields was visualized by silver impregnation, and the loss of various types of non-principal cells was studied by immunostaining for the calcium binding proteins parvalbumin, calbindin-D28k and calretinin, as well as for somatostatin. In the first series of experiments various concentrations (ranging from 0.1 to 1 mg/ml) and volumes (0.5-2 microliters) of kainate were tested to induce reproducible damage in the contralateral hippocampus. The optimal dose, employed in the subsequent vulnerability studies, was found to be 3 x 0.5-microliter injections (over a period of 10 min) of a concentration of 0.33 mg/ml under ether anaesthesia, which was discontinued immediately after injection. Anaesthesia with equithesin was found to prevent contralateral cell death. Most if not all pyramidal cells in the CA3 region degenerated on the ipsilateral side, whereas the dentate granule cells, and the majority of CA1 pyramidal cells were resistant. A strikingly different pattern was found on the contralateral side, where CA1 pyramidal cells were almost completely lost, but the CA3 region (with the exception of CA3c) and the dentate gyrus remained intact. Three subpopulations of non-principal cells were found to be vulnerable in both hemispheres, the hilar somatostatin cells, spiny calretinin cells and mossy cells, as well as the spiny calretinin cells in stratum lucidum of CA3. The other subpopulations were resistant, except for those within the effective injection site. We propose that the "distant" (contralateral) damage resembles the pattern, and probably also the mechanism, of cell death in human temporal lobe epilepsy, whereas the ipsilateral damage does not.
 ...
PMID:Selective neuronal death in the contralateral hippocampus following unilateral kainate injections into the CA3 subfield. 824 63

Somatostatin-, neuropeptide Y-, neurokinin B- and cholecystokinin-containing neurons were investigated in the rat hippocampus in two chronic models of temporal lobe epilepsy, i.e. 30 days after rapid kindling or electrically induced status epilepticus (post-status epilepticus). After rapid kindling, somatostatin immunoreactivity was strongly increased in interneurons and in the outer and middle molecular layer of the dentate gyrus. In four of six post-status epilepticus rats (status epilepticus I rats), somatostatin immunoreactivity was slightly increased in the dorsal but decreased in the ventral dentate gyrus and molecular layer. Somatostatin immunoreactivity decreased in neurons of the dorsal hilus in the two other post-status epilepticus rats investigated, while a complete loss was found in the respective ventral extension (status epilepticus-II rats). These changes were associated with a different extent of neurodegeneration as assessed by Nissl staining. Similarly, neuropeptide Y immunoreactivity was enhanced in neurons of the hilus and in the middle and outer molecular layer of the dentate gyrus in the dorsal hippocampus of rapidly kindled and status epilepticus-I rats. Neuropeptide Y and neurokinin B immunoreactivity was enhanced in the mossy fibers of all post-status epilepticus rats, but not in the rapidly kindled rats. In status epilepticus-II rats, neuropeptide Y-and neurokinin B-positive fibers were also detected in the infrapyramidal region of the stratum oriens of CA3 and in the inner molecular layer of the dentate gyrus in the dorsal and ventral hippocampus respectively, labeling presumably sprouted mossy fibers. Increased staining of neuropeptide Y and neurokinin B was found in the alveus after rapid kindling. Cholecystokinin immunoreactivity was markedly increased in the cerebral cortex, Ammon's horn and the molecular layer of the dentate gyrus in the ventral hippocampus of rapidly kindled and post-status epilepticus rats. The lasting changes in the immunoreactive pattern of various peptides in the hippocampus may reflect functional modifications in the corresponding peptide-containing neurons. These changes may be involved in chronic epileptogenesis, which evolves in response to limbic seizures.
 ...
PMID:Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy. 859 52

Forty-nine consecutive patients undergoing anteromedial temporal lobe resection for medically intractable temporal lobe seizures, and averaging 2 yr (range 6 mo to 4 yr) postoperative follow-up, were selected for a retrospective study. This study correlated magnetic resonance imaging (MRI) derived hippocampal volumetrics, preoperative demographics, postoperative seizure control, and tissue analysis, including hippocampal CA (cornu ammonis) field neuronal, and glial cell counts, and immunohistochemistry (IHC) evidence for dentate sprouting and reorganization. These measures were compared in hippocampi with or without an adjacent presumptive epileptogenic temporal lobe mass. Mesial temporal sclerosis (MTS) was defined as > 50% neuronal cell loss averaged across all CA fields with NPY (neuropeptide-y) and somatostatin reorganization. These patients may or may not include granule cell sprouting as determined by dynorphin staining. Patients were divided into two groups based on CA field neuronal cell counts, one averaging > 50% cell loss and one averaging < 50% cell loss. For the MTS group (N = 38), 89% had significant volumetric atrophy of the ipsilateral hippocampus, 74% had dentate reorganization, and complete seizure control was seen in 76% of these patients. In one subgroup of the < 50% cell loss group, patients with medial temporal lobe epilepsy caused by a mass in the medial temporal lobe (mass group) (N = 6), 33% demonstrated significant volumetric atrophy of the hippocampus ipsilateral to the mass, 0% had dentate sprouting, and seizures were completely controlled in 67%. For the second subgroup of the < 50% cell loss group, patients without mass lesions (N = 5) who were classified as the paradoxical medial temporal lobe epilepsy group (paradoxical group), 20% had ipsilateral hippocampal atrophy, 0% had dentate reorganization, and complete seizure control was seen in 60% of these patients. In conclusion, for the MTS group, hippocampal atrophy proven by MRI volumetrics was highly predictive of significant neuronal cell loss and an excellent indicator of success. However, in patients who had a foreign mass, hippocampal atrophy was not necessarily indicative of significant neuronal cell loss and MRI volumetrics was not a factor in the determination of a successful outcome. Furthermore, patients without mass lesions who have normal volumetrics but demonstrate hippocampal disease through invasive electrode monitoring, are likely to have paradoxical medial temporal lobe epilepsy, seizures beginning at a later age, and a lower, but not insignificant, success rate than the classical mesial temporal sclerosis group.
 ...
PMID:Hippocampal MRI volumetrics and temporal lobe substrates in medial temporal lobe epilepsy. 875 Mar 18


<< Previous 1 2 3 4 5 6 7 Next >>