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| 2. |
- Gustafsson Brywe, Katarina, 1965, et al.
(author)
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Growth hormone-releasing peptide hexarelin reduces neonatal brain injury and alters Akt/glycogen synthase kinase-3beta phosphorylation
- 2005
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 146:11, s. 4665-72
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Journal article (peer-reviewed)abstract
- Hexarelin (HEX) is a peptide GH secretagogue with a potent ability to stimulate GH secretion and recently reported cardioprotective actions. However, its effects in the brain are largely unknown, and the aim of the present study was to examine the potential protective effect of HEX on the central nervous system after injury, as well as on caspase-3, Akt, and extracellular signal-regulated protein kinase (ERK) signaling cascades in a rat model of neonatal hypoxia-ischemia. Hypoxic-ischemic insult was induced by unilateral carotid ligation and hypoxic exposure (7.7% oxygen), and HEX treatment was administered intracerebroventricularly, directly after the insult. Brain damage was quantified at four coronal levels and by regional neuropathological scoring. Brain damage was reduced by 39% in the treatment group, compared with vehicle group, and injury was significantly reduced in the cerebral cortex, hippocampus, and thalamus but not in the striatum. The cerebroprotective effect was accompanied by a significant reduction of caspase-3 activity and an increased phosphorylation of Akt and glycogen synthase kinase-3beta, whereas ERK was unaffected. In conclusion, we demonstrate for the first time that HEX is neuroprotective in the neonatal setting in vivo and that increased Akt signaling is associated with downstream attenuation of glycogen synthase kinase-3beta activity and caspase-dependent cell death.
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| 3. |
- Gustafsson Brywe, Katarina, 1965, et al.
(author)
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IGF-I neuroprotection in the immature brain after hypoxia-ischemia, involvement of Akt and GSK3beta?
- 2005
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In: Eur J Neurosci. - : Wiley. - 0953-816X. ; 21:6, s. 1489-502
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Journal article (peer-reviewed)abstract
- Insulin-like growth factor I (IGF-I) is a neurotrophic factor that promotes neuronal growth, differentiation and survival. Neuroprotective effects of IGF-I have previously been shown in adult and juvenile rat models of brain injury. We wanted to investigate the neuroprotective effect of IGF-I after hypoxia-ischemia (HI) in 7-day-old neonatal rats and the mechanisms of IGF-I actions in vivo. We also wanted to study effects of HI and/or IGF-I on the serine/threonine kinases Akt and glycogen synthase kinase 3beta (GSK3beta) in the phophatidylinositol-3 kinase (PI3K) pathway. Immediately after HI, phosphorylated Akt (pAkt) and phosphorylated GSK3beta (pGSK3beta) immunoreactivity was lost in the ipsilateral and reduced in the contralateral hemisphere. After 45 min, pAkt levels were restored to control values, whereas pGSK3beta remained low 4 h after HI. Administration of IGF-I (50 microg i.c.v.) after HI resulted in a 40% reduction in brain damage (loss of microtubule-associated protein) compared with vehicle-treated animals. IGF-I treatment without HI was shown to increase pAkt whereas pGSK3beta decreased in the cytosol, but increased in the nuclear fraction. IGF-I treatment after HI increased pAkt in the cytosol and pGSK3beta in both the cytosol and the nuclear fraction in the ipsilateral hemisphere compared with vehicle-treated rats, concomitant with a reduced caspase-3- and caspase-9-like activity. In conclusion, IGF-I induces activation of Akt during recovery after HI which, in combination with inactivation of GSK3beta, may explain the attenuated activation of caspases and reduction of injury in the immature brain.
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| 4. |
- Gustavsson, Malin, 1975, et al.
(author)
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Global gene expression in the developing rat brain after hypoxic preconditioning: involvement of apoptotic mechanisms?
- 2007
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In: Pediatr Res. ; 61:4, s. 444-50
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Journal article (peer-reviewed)abstract
- Exposure to hypoxia before hypoxia-ischemia (HI) confers substantial protection referred to as preconditioning (PC). We hypothesized that PC induces critical changes of genes related to apoptotic cell death to render the brain more resistant. PC hypoxia (8% O2, 36 degrees C, 3 h) was induced in rats on postnatal day (PND) 6, and the rats were killed at 0, 2, 8, and 24 h. Total RNA was extracted from cerebral cortex and analyzed using Affymetrix rat genome 230 2.0 array. PC induced significant changes in 906 genes at 0 h, 927 at 2 h, 389 at 8 h, and 114 at 24 h. Ontology analysis revealed significant alterations in genes involved in cell communication, signal transduction, transcription, phosphorylation, and transport. Genes involved in cell death/apoptosis as well as those related to brain development (cell differentiation, neurogenesis, organogenesis, blood vessel development) were overrepresented. A detailed analysis demonstrated that 77 significantly regulated genes were involved in apoptosis, specifically related to the Bcl-2 family, JNK pathway, trophic factor pathways, inositol triphosphate (PI3) kinase/Akt pathway, extrinsic or intrinsic pathway, or the p53 pathway. The study supports that the epidermal growth factor receptor family, mitogen-activated protein kinase phosphatases, and Bcl-2-related proteins and the PI3 kinase/Akt pathway may have roles in providing resistance in the developing central nervous system (CNS).
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| 5. |
- Gustavsson, Malin, 1975, et al.
(author)
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Hypoxic preconditioning confers long-term reduction of brain injury and improvement of neurological ability in immature rats
- 2005
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In: Pediatr Res. ; 57:2, s. 305-9
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Journal article (peer-reviewed)abstract
- Exposure to preconditioning (PC) hypoxia 24 h before a severe hypoxic-ischemic (HI) insult reduces development of injury in the immature brain. Several protective regimens have proved effective in the short-term but not in the long-term perspective. The aim of the present study, therefore, was to evaluate the PC effect on long-term morphologic and neurologic outcome in the developing brain. Six-day-old rats were subjected to hypoxia (36 degrees C, 8.0% O2; PC/HI group) and sham controls to normoxia (36 degrees C; HI group) for 3 h. Twenty-four hours later, all rats were exposed to cerebral HI produced by unilateral carotid artery occlusion combined with 1 h, 15 min of hypoxia (36 degrees C, 7.7% O2). A cylinder test was used to evaluate forelimb asymmetry to determine sensorimotor function at 4, 6, and 8 wk of age. Spatial/cognitive ability was assessed by Morris water maze trials at 7 wk of recovery. Neuropathologic analysis was performed 8 wk after insult. Brain damage was reduced (p<0.0001) in PC/HI (45.0+/-11.1 mm3) in comparison with HI (159.3+/-12.2 mm3) rats. A bias for using the ipsilateral forelimb in wall movements was observed in the cylinder test in HI compared with PC/HI rats at 4 (p<0.001), 6 (p<0.01), and 8 (p<0.0001) wk of age. Results of the Morris water maze test revealed differences (p<0.0001) in average path length between groups on the third and fourth day of trials. Hypoxic PC before HI reduced brain injury by 72% at 8 wk after the insult and provided long-term improvement of sensorimotor and spatial/cognitive functions.
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| 6. |
- Gustavsson, Malin, 1975, et al.
(author)
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Vascular response to hypoxic preconditioning in the immature brain
- 2007
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In: J Cereb Blood Flow Metab. ; 27:5, s. 928-38
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Journal article (peer-reviewed)abstract
- We hypothesized that hypoxic preconditioning (PC) modifies the microvasculature in the immature brain and thereby affects the cerebral blood flow (CBF) during a subsequent hypoxic-ischemic (HI) insult. On postnatal day 6 rats were exposed to hypoxia (36 degrees C, 8.0% O2) or normoxia for 3 h. Unilateral HI (unilateral carotid ligation and 8% hypoxia) was induced 24 h later. Cortical CBF was measured with the 14C-iodoantipyrine technique (at the end of HI) or with laser Doppler flowmetry (Perimed PF5001) before and during HI. At 0, 2, 8, and 24 h cerebral cortex was sampled and analyzed with gene arrays (Affymetrix 230 2.0). L-nitroarginine or vehicle was administrated before hypoxic PC or 30 mins before HI followed by CBF measurement (laser Doppler) during subsequent HI. Twenty-four hours after PC animals were perfusion-fixed and brains immunolabeled for von Willebrand factor and vascular density was determined by stereological quantification. The decrease in CBF during HI was attenuated significantly in PC versus control animals (P<0.01), as detected by both techniques. Several vascular genes (Angpt2, Adm, Apln, Vegf, Flt1, Kdr, Pdgfra, Agtrap, Adora2a, Ednra, serpine1, caveolin, Id1, Prrx1, Ero1l, Acvrl1, Egfl7, Nudt6, Angptl4, Anxa2, and NOS3) were upregulated and a few (Csrp2, Adora2b) were downregulated after PC. A significant increase in vascular density (P<0.05) was seen after PC. Nitric oxide synthase inhibition did not affect CBF during HI after PC. In conclusion, hypoxic PC upregulates vascular genes, increases vascular density and attenuates the decrease of CBF during a subsequent HI, which could contribute to tolerance.
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| 7. |
- Hagberg Gustavsson, Malin
(author)
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Forskning för djurens skull - katt, hund & häst 2018
- 2019
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Reports (other academic/artistic)abstract
- Rapporten som du nu har i din hand presenterar ett axplock av de resultat som kom ut av Sveriges lantbruksuniversitets (SLU) forskning om katter, hundar och hästar under förra året. Djurhälsa och djurvälfärd är centrala områden vid SLU och här pågår studier av friska och sjuka djur, deras behov och beteenden. SLU är också det enda universitet i Sverige som utbildar veterinärer, djursjukskötare och husdjursagronomer. Att leva nära djur har positiva effekter på människors välbefinnande och livskvalitet. Många människor finner till exempel en meningsfull fritid i hund-, katt- och hästägande. Inte minst hälsoaspekten av att röra på sig tillsammans med sitt djur får stor betydelse i ett samhälle där de negativa konsekvenserna av ett stillasittande liv uppmärksammas allt mer. Samvaron med sport- och sällskapsdjur är dessutom hälsobringande eftersom den bland annat sänker puls och blodtryck. Vi håller djuren för vår egen skull och på våra villkor vilket gör oss ansvariga för deras hälsa och välmående. Forskning om sport- och sällskapsdjur är viktig i en samhällsutveckling för välmående människor och djur. Utvecklingen i samhället visar att vi behöver öka kunskapen om modern, etisk, hållbar djurhållning, inkluderat hur djuren används för arbete, sport och sällskap. Forskning om djurs spontant uppkomna sjukdomar är grunden för utveckling av förebyggande djurhälsoinsatser och behandling av sjuka djur, men ger också ökad kunskap om de sjukdomar som drabbar både människor och djur. Våra forskare arbetar med alla dessa aspekter av djurhälsa och djurvälfärd.
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| 8. |
- Hagberg, Henrik, 1955, et al.
(author)
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PARP-1 gene disruption in mice preferentially protects males from perinatal brain injury
- 2004
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In: J Neurochem. ; 90:5, s. 1068-75
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Journal article (peer-reviewed)abstract
- Poly(ADP-ribose) polymerase-1 is over-activated in the adult brain in response to ischemia and contributes to neuronal death, but its role in perinatal brain injury remains uncertain. To address this issue, 7-day-old wild-type (wt) and PARP-1 gene deficient (parp+/- and parp-/-) Sv129/CD-1 hybrid mice were subjected to unilateral hypoxia-ischemia and histologic damage was assessed 10 days later by two evaluators. Poly(ADP-ribose) polymerase-1 knockout produced moderate but significant (p < 0.05) protection in the total group of animals, but analysis by sex revealed that males were strongly protected (p < 0.05) in contrast to females in which there was no significant effect. Separate experiments demonstrated that PARP-1 was activated over 1-24 h in both females and males after the insult in neonatal wt mice and rats using immnocytochemistry and western blotting for poly(ADP-ribose). Brain levels of NAD+ were also significantly reduced, but the decrease of NAD+ during the early post-hypoxia-ischemia (HI) phase was only seen in males. The results indicate that hypoxia-ischemia activates Poly(ADP-ribose) polymerase-1 in the neonatal brain and that the sex of the animal strongly influences its role in the pathogenesis of brain injury.
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| 10. |
- Hoffmann, Ruben, et al.
(author)
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Economic Perspective on the Value of Cats and Dogs
- 2019
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In: Society and Animals. - : Brill. - 1063-1119 .- 1568-5306. ; 27, s. 595-613
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Journal article (peer-reviewed)abstract
- Although various benefits of cats and dogs have been extensively studied, their fundamental economic value is poorly understood. Economic values are, in contrast to monetary values, determined subjectively and guide individuals in their decisions. This study presents a conceptual economic model of the value of cats and dogs which provides a basis for future research. Benefits of cats and dogs identified in the literature are categorized in relation to the model. The multidimensional value of these nonhuman animals includes different use and non-use values, for caretakers and other humans. Data from an online survey on the salience (importance of attributes in memory) of cats and dogs in Sweden provide support for the proposed model. It is argued that the subjective well-being approach developed in psychology provides a good starting point for estimating many of the economic values of these animals, but that different types of values may require different approaches.
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