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1

Injections of vehicle, but not cyclosporin A or tacrolimus (FK506), afford neuroprotection following injury in the developing rat brain

100%
Setkowicz Z., Guzik R.
Acta Neurobiologiae Experimentalis
|
2007
|
tom 67
|
nr 4
Susceptibility of the injured rat brain to seizures depends on the developmental stage at which the injury had been inflicted. Our previous study shows that tacrolimus (FK506) and cyclosporin A (CsA) applied following the injury can also decrease or increase the seizure susceptibility in an age-dependent way. To find possible neuronal substrates of the effects, we examined influences of the agents on the injured brain and on its neuronal population. Rat brains were mechanically injured on postnatal days 6 (P6) or 30 (P30). Twenty minutes and 24 hours following the injury, FK506 or CsA were injected in clinically used pharmaceutical formulations (Prograf® or Sandimmun®, respectively). The brains were fixed on postnatal day 60 and processed for histological examinations. To detect if negative effects of the injury could be abolished by the treatments, we examined the brain weight, the size of the injured region, and the nerve cell density, including the density of calretinin- and parvalbumin-immunopositive cells. We have found that long-term effects of treatments with the FK506- and CsA-containing pharmaceutical formulations were never better than those of the vehicle alone (Cremophor and ethanol mixture). Moreover, the treatments could even amplify negative consequences of the injury alone. It could, therefore, be concluded that all the neuroprotective effects observed in the present study resulted exclusively from the influence of the vehicle alone. These effects of the brain injury and of subsequent treatments performed at different developmental stages were considered as possible determinants of further increase or decrease in susceptibility to seizures observed in adulthood.
2
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Rola diety w leczeniu chorób neurodegeneracyjnych

100%
Lipiec O., Setkowicz Z.
Wszechświat
|
2017
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tom 118
|
nr 01-03
3

Changes in reactive behaviours of macrophages and astrocytes show opposite trends in the injured brain of cday-old rat exposed to gamma-irradiation at different stages of prenatal development

81%
Setkowicz Z., Baran A., Janeczko K.
Acta Neurobiologiae Experimentalis
|
1999
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tom 59
|
nr 3
4

Susceptibility to electroshock-induced seizures in rats following neocortical injuries at different developmental stages

81%
Uram L., Gzielo-Jurek K., Setkowicz Z., Janeczko K.
Acta Neurobiologiae Experimentalis
|
2011
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tom 71
|
nr 1
Brains injured at different developmental stages may acquire different susceptibility to epileptiform activities. Epileptogenesis appears to be triggered by age-dependent reactive processes including gliosis and formation of aberrant axonal connections in the tissue surrounding the lesion site. The present study focuses on relations between brain injuries at different developmental stages and subsequent susceptibility to seizures in adulthood. In 6- and 30-day-old Wistar rats (P6s and P30s, respectively), a mechanical injury was performed in the left cerebral hemisphere. From the postnatal day 60, the injured rats and non-injured controls underwent 21 daily electrical stimulations to evoke seizures. Tonic and clonic reactivity to electric stimulation in P6s and P30s showed considerably different profiles contrasting with those previously observed following pilocarpine or kainic acid administration in the same experimental paradigm. In P6s intensity of tonic seizures was significantly higher than that in controls or in P30s while clonic seizured revealed no intergroup difference. The results proved that the observed phenomena depended on the model used for experimental exploration of the problem but their structural determinants remain obscure.
5

LPS injection on the 6th and 30th postnatal days modulates differently seizure-induced microglial transformation in adult rats’ brain cortex. Morphometric analysis

81%
Kosonowska E., Janeczko K., Setkowicz Z.
Acta Neurobiologiae Experimentalis
|
2017
|
tom 77
|
nr Suppl.1
INTRODUCTION: According to previous studies, neuroinflammation may lead to an increase in seizure susceptibility and trigger epileptogenesis. However, emerging experimental evidence indicates that early age inflammation acting as a preconditioning factor may also have protective effects. Microglia are the immune competent cells of the CNS. After inflammation cellsretracttheir branches and transform into macrophages. Parameters of this morphological changes can be used as parameters of tissue reactivity to inflammation and seizures. AIM(S): The aim of this study was to examine the long term effects of systemic inflammation induced at different postnatal developmental stages on the range of morphological changes in microglial cells within brain cortex in response to status epilepticus experimentally evoked in adulthood. METHOD(S): Wistar rats were injected intraperitoneally with LPS on postnatal days 6 (P06) or 30 (P30). Two-month-old animals were injected with pilocarpine to evoke status epilepticus and sacrificed three days later. Brain sections were then processed for Iba-1 immunohistochemistry. A set of photographs were taken from several locations in the brain cortex and the automated Sholl analysis and morphometric measurements were performed. RESULTS: LPS injection alone on P06 and P30 causes significant decrease of critical radius and enclosing radius and significant increase of solidity. After seizures induced in adulthood statistically significant differences in all examined morphological parameters in both LPS-treated groups were observed. The morphology of microglia in rats’ cortex in P06 and P30 group after seizures is significantly closer to morphology of microglial cells in naïve rats. CONCLUSIONS: This imply that microglia in adult rat’s cortex after LPS injection alone in P06 or P30 are more ramified closer to the cell body. Also the longest processes are shorter after LPS injection than in naïve rats. This might result from long-term changes in nervous-tissue reactivity – preconditioning. FINANCIAL SUPPORT: Supported by NCS GRANT: UMO-2012/05/B/NZ4/02406.
6

The brain anatomy imaging after prolonged ketogenic diet feeding in rats

81%
Gzielo K., Kielbinski M., Jasinski K., Setkowicz Z.
Acta Neurobiologiae Experimentalis
|
2017
|
tom 77
|
nr Suppl.1
INTRODUCTION: Ketogenic diet (KD) results in mild to moderate ketosis, which in turn can significantly change the metabolic balance in the brain. The effects of KD are broadly studied in search of potential clinical uses, such as reducing seizure severity in epilepsy, or providing adjunctive therapy for cancer, Alzheimer’s or Parkinson’s disease. The exact mechanism of those putative neuroprotective effects of KD is, however, still poorly understood. AIM(S): Here, we have checked if prolonged ketogenic diet changed beta hydroxy butyrate(BHB) and epididymal fat levels. The crucial thing was to determine how the ketogenic diet affects brain volume and anatomy. METHOD(S): Male Wistar rats were assigned into two experimental groups: one was given KD for 4 months (n=10), the other (n=11) was fed normal laboratory chow (N). After 4 months, rats were sacrificed. Blood samples were collected and BHB levels measured with ELISA. T2-weighed ex vivo images of extracted brains, taken with a 9.4 T magnetic resonance scanner were obtained at the Institute of Nuclear Physics, at XY resolution of 0.025 mm and voxel depth of 0.25 mm. Using a computer-assisted Cavalieri method, the volumes of the entire brain, hippocampus and brainstem structures (midbrain, pons) were estimated. Volumes were compared between groups to show differentially affected regions. Student’s t‑tests was used for statystical analysis. RESULTS: We have observed increased epididymal fat and elevated BHB levels in KD in comparison to the N group (p<0,000001). Additionally we have found a significant reduction in overall pontine volume in the KD group after the 4-month feeding period. CONCLUSIONS: Our results indicate that the prolonged ketogenic feeding was successful in inducing metabolic changes in KD animals. Observed differences in pontine volume in rats fed a ketogenic diet may lead to modification of feeding behavior. These imapairments in food-intake process may be strictly involved with parabrachial structures which are engaged in regulating appetitive behavior. FINANCIAL SUPPORT: Supported by NCS GRANT: UMO-2015/17/B/NZ7/02953.
7

Changes in the distribution of immunoglobulin G cellular uptake in the injured cerebral hemisphere in mice

80%
Janeczko K., Pawlinski R., Setkowicz Z.
Folia Histochemica et Cytobiologica
|
1993
|
tom 31
|
nr 4
8

Interleukin-1 beta affects the macrophage recruitment and proliferation in the injured brain of 6-day-old rat

80%
Pawlinski R., Setkowicz Z., Malodzinska K., Janeczko K.
Acta Neurobiologiae Experimentalis
|
1999
|
tom 59
|
nr 4
9

W zdrowym ciele zdrowy duch

80%
Setkowicz Z.
Wszechświat
|
2008
|
tom 109
|
nr 01-03
29-30
10

Effects of FK506 or cyclosporine A on the developing hippocampal formation

71%
Setkowicz Z., Radomska K., Rogoz K., Uran L., Janeczko K.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 1
Tacrolimus (FK506) and cyclosporin A (CsA) are immunosupressants widely used in transplantology. They can also protect neurons in several models of brain damage. Prolonged administration of the drugs has many negative neurological side-effects. The effects might depend on the developmental stage but appropriate investigations have been particularly rare. The present study focuses on long-term changes evoked by the drugs in the developing hippocampal formation. Six- and 30-day-old rats (P6s and P30s, respectively) were injected with FK506 or CsA in their pharmaceutical formulas containing a mixture of ethyl alcohol and Cremophor as a vehicle. Controls received the vehicle alone. When the rats were 60-day-old, sizes of their hippocampal formation, densities of calretinin-(CR+), parvalbumin-immunopositive (PV+) neurons and S100β protein-positive (S100β+) astrocytes were assessed. In P6s and P30s treated with CsA in its farmaceutical formula, the size of hippocampal formation was reduced. However, injections of the vehicle alone led to similar effects. In P30s, FK506 decreased the density of CR+ neurons but the vehicle had again the same negative effect. The only signifi cant change in relation to vehicle-treated animals was a decrease in density of PV+ neurons in CsA-treated P30s. In P6s, FK506 dissolved in the vehicle increased the density of S100β+ astrocytes only in relation to naive but not vehicle-treated controls. Longterm effects of FK506 or CsA in their pharmaceutical formulas were mostly negative. Interestingly, they could also be obtained by application of the vehicle alone. Therefore, clinical and experimental effects of FK506 or CsA cannot exclusively be attributed to the drugs themselves abut also to the vehicle which appears to be not biologically neutral.
11

Alterations in brain development in rats treated with immunosuppresant drugs Sandimmune and Prograf and their vehicle components

71%
Uram L., Gzielo-Jurek K., Janeczko K., Kielbinski M., Setkowicz Z.
Acta Neurobiologiae Experimentalis
|
2013
|
tom 73
|
nr 1
Cyclosporin A and tacrolimus are powerful immunosuppressants used as post-operation medication after allogenic transplantations. Unfortunately, the drugs Sandimmune (cyclosporin A) and Prograf (tacrolimus) exhibit negative side effects. These side effects may be linked not only to the active ingredients themselves, but also to the vehicle used for their delivery – Cremophor EL and/or ethanol. Sandimmune, Prograf, ethanol, Cremophor EL or Cremophor EL with ethanol (i.e. the complete vehicle) in a saline solution were administered to male Wistar rats either on 6th and 7th or 30th and 31st day postnatally. The functional changes in the nervous system elicited by these substances were assessed by observing the intensity of seizures induced by a single i.p. injection of pilocarpine at 60th postnatal day. Brain anatomy was also analyzed by comparing brain mass, lateral ventricle relative area, thickness of cerebral hemisphere wall, relative size of the hippocampus as well as total density of cresyl violet-stained neurons in the cerebral hemisphere walls between control and experimental animals. Our data point to a significant effect of all tested substances on central nervous system development. The greatest effects on seizure severity and brain structure were associated with the complete vehicle. Such effects (although less sever) were also observed for Cremophor EL and ethanol given separately.
12

Intralesional injection of interferon gamma affects reactive proliferation of astrocytes in the neonatal rat brain. A preliminary study of the age-dependent effect

71%
Pawlinski R., Setkowicz Z., Ziaja M., Soltys Z., Janeczko K.
Folia Histochemica et Cytobiologica
|
1999
|
tom 37
|
nr 4
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