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Ketanserin reduces the postischemic EEG and behavioural changes following Endothelin-1-induced occlusion of the middle cerebral artery in conscious rats

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Moyanova S., Kortenska L., Kirov R., Itzev D., Usunoff K.
Open Medicine
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2008
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vol. 3
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issue 4
406-416
EN
We modeled the common clinical conditions of human stroke in fully conscious rats through an occlusion of the middle cerebral artery (MCAO) by means of unilateral microinjection of Endothelin-1 (ET1) in the vicinity of the artery (EMCAO model). Since the role of serotonin (5-HT) system in the regulation of the cerebral blood flow has been known for long time and no data are available at present for the effects of 5-HT antagonists in focal ischemia models, we further tested whether a blockade of the serotonin-2A (5-HT2A) receptors by ketanserin (20 min post-ET1) would diminish the late EMCAO-induced functional and morphological changes. The long-term neurological (postural reflex) and electroencephalogram (EEG) changes in the somatosensory cortical region (S1FL) were used to assess the effects of ketanserin on the post-ischemic changes. The study was supplemented by a histopathological examination of S1FL area and striatum of both hemispheres. The EMCAO/ ketanserin-treated rats showed much smaller neurological deficits than the EMCAO rats treated with vehicle. This effect was observed on day 3 and lasted until the end of experiments-14 days after EMCAO. The depression of alpha and beta EEG frequencies found after EMCAO was significantly and earlier restored following ketanserin. Notably, there was not augmentation of the pathological slow EEG waves at day 3 post-ET1 in the EMCAO ketanserin-treated rats compared with that observed in the EMCAO vehicle-treated rats. Although there were mild morphological changes in the penumbral S1FL cortical region after EMCAO, ketanserin reduced the histopathological difference between the ipsilateral and contralateral cortical S1FL regions, but did not change the difference between striatum of both sides. Ketanserin reduced the infarct size in ipsilateral hemisphere (mainly cortex). In conclusion, the results showed that treatment with ketanserin at the early stage of stroke may reduce the consequences of ischemia by improvement of functional and morphological recovery at later stages. Ketanserin appears to be a promising candidate for mitigating the consequences of stroke.
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Age-related changes in substance P-immunoreactive nerve structures of the rat recto-anal region

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Lazarov N., Itzev D., Usunoff K., Negrev N., Radomirov R.
Open Medicine
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2010
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vol. 5
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issue 3
358-364
EN
The recto-anal region is innervated by extrinsic and intrinsic nerves and a number of neuropeptides including substance P (SP) have been suggested to participate in the regulation of intestinal movements. We examined the age-related changes in the distribution of SP-immunoreactive nerve structures in the distal part of the rat large intestine. Using immunohistochemistry, the presence of SP was studied in fresh tissues from Wistar rats at different ages taken at three sampling sites, the distal rectum, anal canal and internal anal sphincter. In the 15-day old rats the myenteric plexus of the distal rectum and anal canal was well outlined by numerous SP-immunoreactive varicose nerve fibres encircling immunonegative perikarya. In the circular muscle layer, nerve fibres and small nerve bundles ran parallel to the muscle cells, while in the longitudinal muscle layer, only occasional nerve fibres were seen. At the level of the internal anal sphincter, no myenteric ganglia were present. Here, thin varicose fibers ran parallel to the smooth muscle cells. In the 3-month old rats, a larger number of intensely staining SP-immunoreactive nerve fibres were found and in the circular muscle layer, thicker nerve strands were observed. In the 26-month old rats, the density and staining intensity of SP-immunopositive nerve fibres in the myenteric plexus was lower than in the 3-month-old rats. Similar changes in the SP-immunostained fibres in the internal anal sphincter were observed. Degenerative alterations in SP-containing fibres during aging appear to play a role in ano-rectal motility and sphincter control.
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