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1

Matrix metalloproteinases after cerebral photothrombotic stroke in rat

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Aleksy M., Rogozinska K., Skangiel-Kramska J.
Acta Neurobiologiae Experimentalis
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2006
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tom 66
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nr 4
2

Nuclear localization of matrix metalloproteinases in neurons after stroke in the rat cortex

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Aleksy M., Rogozinska K., Skangiel-Kramska J.
Acta Neurobiologiae Experimentalis
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2007
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tom 67
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nr 3
3

Delayed activation of metalloproteinase 9 after photothrombotic stroke in aged mice

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Aleksy M., Kossut M., Skangiel-Kramska J.
Acta Neurobiologiae Experimentalis
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2009
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tom 69
|
nr 1
Age-related brain injuries, including ischemia, can lead to neurological disabilities, functional decline of the brain and poor recovery. Metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) belonging to a large family of zinc-dependent proteinases, play an important role in development and neuronal plasticity, cell migration, angiogenesis and wound healing. After stroke, activation of MMPs is strongly up-regulated. The aim of this study was to compare the time course of activation of MMP- 9 and MMP-2 in the cerebral cortex of young (3ñ4 months old) and aged (12ñ13 months old) mice following focal photothrombotic stroke. To reveal metalloproteinases MMP-9 and MMP-2 activity in situ zymography and SDS-PAGE zymography were used. In young mice, pronounced induction of MMP-9 activity was found one day after stroke and remained at high level 7 and 14 days after infarct. In aged mice, however, MMP-9 activity could be seen not earlier than 14 days post-stroke. Photothrombotic stroke did not affect MMP-2 activity, which remained at stable, constitutive level during whole examined post stroke time period. In both young and aged mice, MMP-2 activity could be detected in sham operated animals, while constitutive MMP-9 activity was not observed. We speculate that the delayed activation of MMP-9 in aged mice may be one of the reasons of lesser ability to recover by old patients. Supported by Polish-German grant nr P-N/026/2006
4

How photothrombotic stroke affects extracellular matrix?

100%
Nowicka D., Karetko M., Aleksy M., Skangiel-Kramska J.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 3
Perineuronal net (PN), a lattice-like structure surrounding certain neurons, represents a special form of extracellular matrix of the brain. The role of this structure remains elusive. It has been suggested to regulate neuronal plasticity, accumulate trophic molecules and protect neurons from damaging factors. Here we studied whether PN-enwrapped neurons are protected against ischemic injury. To this aim we performed cortical photothrombotic stroke in rats and investigated PNs and their co-localization with Fluoro Jade C (FJ), a marker of rapid cell death. We found that in the ischemic core 4 h after the stroke still PNs were observable, none of them around FJ-positive neurons. No PNs were detected after 24 h. In the peri-infarct area, a huge loss of PNs was observed 24 h after stroke, followed by a partial restoration 30 days post-infarct. Similar effect was found in remote cortical areas, except that in this case the restoration was almost complete already 7 days after stroke. No FJ staining was observed outside ischemic core. These results suggest that in areas that are not directly damaged, ischemic insult disrupts PNs but the neurons survive this disruption. Supported by MNiSW Grant N3030300832/0474.
5

Activity of metalloproteinases in the brain of young and old mice after focal phototrombotic stroke

100%
Aleksy M., Skangiel-Kramska J., Kossut M.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 3
Aging is a major risk factor for ischemia. Old experimental animals demonstrate bigger infarct progression and more extensive neuronal degeneration after stroke compared to young animals. Activation and expression of metalloproteinases (MMPs), MMP- 2 and MMP-9 particularly, is strongly up-regulated after stroke and it was proved to have a detrimental role. The present study was designed to compare MMPs activity in old and young brains after ischemia. Cortical photothrombotic stroke was induced in young (3–4 months) and aged (12–13 months) C57/BL mice. MMPs activity on the infarcted area and surrounding tissue was examined at 1, 7 and 14 days after stroke. Although in situ zymography revealed that the time-course of gelatinolytic activity and the pattern of distribution of digested products were similar in both groups, old mice exhibited stronger fl uorescein signals of MMPs activity in the ischemic and peri-infarct areas, as compared to young animals. Analysis of brain homogenates by SDS-Page zymography showed the upregulation of MMP-9 activity after stroke in old brains, while in young brains activity of this metalloproteinase was detected at low level. MMP-2 activity remained at stable and comparable level in both groups at all investigated time-points. These results suggest that old brains exhibit stronger proteolytic reaction after stroke, which may contribute to a more severe course of the disease. Supported by Polish-German Grant P-N/026/2006 and Statutory Funds.
6

Influance of age upon photothrombotic stroke in mice

100%
Liguz-Lecznar M., Aleksy M., Skangiel-Kramska J., Kossut M.
Acta Neurobiologiae Experimentalis
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2009
|
tom 69
|
nr 3
Stroke is one of the leading causes of death and disability in humans. Animal models of stroke simulate the human pathology and can help to develop the effective therapies. One of such models is the photothrombosis model in which cerebral ischemia is induced photochemically by injecting the photosensitive dye. The advantages of this model are the small infarct size, minimal surgical manipulation of the animal. Despite the strong connection of stroke with aging process, the majority of experimental studies are conducted in young or adult animals. Here we have used young (3 months old) and aged (12 months old) mice to produce the small (about 2 mm in diameter) infarct neighboring the primary somatosensory barrel cortex area and including the whole depth of cortex. After 7-day reconvalescence we have analyzed the presence and size of the evoked infarct. In both groups stroke has evoked similar changes in cortex cytoarchitecture, however we found that aging has decreased the method effectiveness of about 25%. Moreover, comparing to young animals, in old mice size and extent of infarct evoked with the same parameters and conditions were much less unrepeatable. It can be associated with changes of the nervous system physiology with age that concern the blood fl ow, diameter of blood vessels, metabolism and physiology of neurons and glial cells. Alternatively, older mice may have adapted functionally to age-dependent damage. Supported by the Scientifi c Network: Biovision SNB-504-8.
7

Spatiotemporal dynamics of astroglial and microglial responses after photothrombotic stroke in the rat brain

88%
Nowicka D., Rogozinska K., Aleksy M., Witte O. W., Skangiel-Kramska J.
Acta Neurobiologiae Experimentalis
|
2008
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tom 68
|
nr 2
The effects of photothrombotic stroke in primary somatosensory cortex on astroglial and microglial activation in various regions of lesioned brain were examined at different time points, using immunohistochemistry and lectin binding. The increase in GFAP expression was observed exclusively in the ipsilateral hemisphere, both in the perilesional area and cortical regions distant from the infarct. This remote increase was detectable up to sixty days after the infarct. Transient GFAP elevation was also found in the hippocampus one day after photothrombosis, whereas it was more prolonged in amygdala, as demonstrated at four days after lesion. In contrast to a widespread astrocytic activation, the microglial response was shortlasting and local, confined to lesion and perilesional area. Widespread and prolonged activation of astrocytes after stroke may provide factors promoting slowly developing recovery processes in the whole brain, while microglial response seems to be involved in local repair and removal of cellular debris.
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