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| 2. |
- Jakobsson, Johan, et al.
(författare)
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Evidence for disease-regulated transgene expression in the brain with use of lentiviral vectors.
- 2006
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 1097-4547 .- 0360-4012. ; 84:1, s. 58-67
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Tidskriftsartikel (refereegranskat)abstract
- In this study we have developed and validated a novel approach of transgene regulation in the brain. By using lentiviral vectors that incorporate promoters of genes that are up-regulated during different pathological states, we were able to regulate transgene expression in accordance with the disease process. When using a glial fibrillary acidic protein promoter, efficient disease regulation in glial cells was achieved after an excitotoxic lesion or a 6-hydroxydopamine (6-OHDA) lesion. Transgene expression was physiologically regulated and displayed a dose-dependent increase depending on the severity of lesion. Efficient regulation was also achieved in neurons when using a preproenkephlin promoter in 6-OHDA-lesioned rats, allowing combined regulation and targeting. This disease-regulated approach allows control of transgene expression in the brain without the use of inducer molecules and without overexpression of transactivator proteins
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| 3. |
- Kawa, Lizan, et al.
(författare)
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Expression of galanin and its receptors are perturbed in a rodent model of mild, blast-induced traumatic brain injury
- 2016
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Ingår i: Experimental Neurology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0014-4886 .- 1090-2430. ; 279, s. 159-167
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Tidskriftsartikel (refereegranskat)abstract
- The symptomatology, mood and cognitive disturbances seen in post-traumatic stress disorder (PTSD) and mild blast-induced traumatic brain injury (mbTBI) overlap considerably. However the pathological mechanisms underlying the two conditions are currently unknown. The neuropeptide galanin has been suggested to play a role in the development of stress and mood disorders. Here we applied bio- and histochemical methods with the aim to elucidate the nature of any changes in the expression of galanin and its receptors in a rodent model of mbTBI. In situ hybridization and quantitative polymerase chain reaction studies revealed significant, injury induced changes, in some cases lasting at least for one week, in the mRNA levels of galanin and/or its three receptors, galanin receptor 1-3 (GalR1-3). Such changes were seen in several forebrain regions, and the locus coeruleus. In the ventral periaqueductal gray GalR1 mRNA levels were increased, while GalR2 were decreased. Analysis of galanin peptide levels using radioimmunoassay demonstrated an increase in several brain regions including the locus coeruleus, dorsal hippocampal formation and amygdala. These findings suggest a role for the galanin system in the endogenous response to mbTBI, and that pharmacological studies of the effects of activation or inhibition of different galanin receptors in combination with functional assays of behavioral recovery may reveal promising targets for new therapeutic strategies in mbTBI. (C) 2016 Elsevier Inc. All rights reserved.
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| 4. |
- Rostami, Elham, 1979-, et al.
(författare)
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A Model for Mild Traumatic Brain Injury that Induces Limited Transient Memory Impairment and Increased Levels of Axon Related Serum Biomarkers
- 2012
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 3, s. 115-
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Tidskriftsartikel (refereegranskat)abstract
- Mild traumatic brain injury (mTBI) is one of the most common neuronal insults and can lead to long-term disabilities. mTBI occurs when the head is exposed to a rapid acceleration-deceleration movement triggering axonal injuries. Our limited understanding of the underlying pathological changes makes it difficult to predict the outcome of mTBI. In this study we used a scalable rat model for rotational acceleration TBI, previously characterized for the threshold of axonal pathology. We have analyzed whether a TBI just above the defined threshold would induce any detectable behavioral changes and/or changes in serum biomarkers. The effect of injury on sensory motor functions, memory and anxiety were assessed by beam walking, radial arms maze and elevated plus maze at 3–7 days following TBI. The only behavioral deficits found were transient impairments in working and reference memory. Blood serum was analyzed at 1, 3, and 14 days after injury for changes in selected protein biomarkers. Serum levels of neurofilament heavy chain and Tau, as well as S100B and myelin basic protein showed significant increases in the injured animals at all time points. No signs of macroscopic injuries such as intracerebral hematomas or contusions were found. Amyloid precursor protein immunostaining indicated axonal injuries at all time points analyzed. In summary, this model mimics some of the key symptoms of mTBI, such as transient memory impairment, which is paralleled by an increase in serum biomarkers. Our findings suggest that serum biomarkers may be used to detect mTBI. The model provides a suitable foundation for further investigation of the underlying pathology of mTBI.
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| 5. |
- Rostami, Elham, 1979-, et al.
(författare)
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Alteration in BDNF and its Receptors, Full-length and Truncated TrkB and p75NTR Following Penetration Traumatic Brain Injury
- 2014
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 13:1542, s. 195-205
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Tidskriftsartikel (refereegranskat)abstract
- The evidence that BDNF is involved in neuroprotection, neuronal repair and recovery after traumatic brain injury (TBI) is substantial. We have previously shown that the polymorphism of the human BDNF gene predicts cognitive recovery and outcome following penetrating TBI. The distribution of expression of BDNF and its receptors after penetrating TBI has not been investigated. In this study we examined the expression of these genes in a rat model of penetrating TBI. The injury is produced by a controlled penetration of a 2mm thick needle-shaped object, which is accelerated with a pellet from an air gun. We used in situ hybridization and investigated the mRNA expression of BDNF and its receptors: the full-length and the truncated TrkB and p75(NTR), from 1 day to 8 weeks following penetrating TBI. In addition, the protein level of BDNF in frontal cortex and hippocampus was measured by reverse phase protein microarray (RPPM). The mRNA expression of BDNF and its receptors decreased in the hippocampus in the border zone ipsilateral to the injury while there was an increase in mRNA expression at the contralateral side. The increase in BDNF mRNA expression in the hippocampus was sustained for 2 weeks following injury, with the highest expression noted in the CA3 cell layer. Furthermore, the protein analysis by RPPM showed increased levels of BDNF in the frontal cortex and the hippocampus up to 2 weeks after TBI. At 8 weeks following injury there was an intense labeling of the truncated TrkB receptor and the p75(NTR) in the area surrounding the cavity. Our study is the first report on the expression of BDNF and its receptors following penetrating TBI and suggests that their expression is altered long after the acute phase of injury. Further studies are needed to investigate if the late expressions of these receptors are beneficial or deleterious. In either case it indicates the possibility to influence the recovery after brain injury during the chronic phase and the development of treatments that may improve the outcome of TBI patients.
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| 6. |
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| 7. |
- Rostami, Elham, 1979-, et al.
(författare)
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Time-Dependent Changes in Serum Level of Protein Biomarkers after Focal Traumatic Brain Injury
- 2015
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Ingår i: International Journal of Neurorehabilitation. - : OMICS Publishing Group. - 2376-0281. ; 2:3, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Serum biomarkers could indicate the pathological changes during the secondary injury process after traumatic brain injury (TBI). Furthermore, they could reflect specific pathological processes following different types of TBI. Here we analyzed time-dependent changes of select protein biomarkers in serum samples collected from a rodent model of penetrating type of injury (pen-TBI). The model is a controlled penetration of a 2 mm thick needle-shaped object, which is accelerated into the brain tissue with a bullet from an air gun. The results obtained in the current study were compared to previously reported results of levels of serum biomarker following a rotational acceleration injury that mimics mild TBI. A total of 24 animals were used, grouped in normal controls, sham-operated and injured animals. The rats were sacrificed at day 1, day 3 and day 14 post-injury and serum samples were analyzed for Tau, neurofilament heavy chain (NF-H), myelin basic protein (MBP), N-cadherin and S100B. We found that all markers but MBP showing a bi-phasic response to injury. Their serum levels significantly increased at day 1, dropped at 3 and increased again at day 14 post-injury. This was in contrast to rotational TBI model where the peak of biomarkers was found at day 3. Our study suggests that pen-TBI results in both acute axonal and neuronal damages as well as delayed changes likely part of the ongoing secondary injury process. These findings illustrate the dynamics of the injury process in pen-TBI and underline the importance of monitoring changes in serum biomarker levels for more accurate assessment of injury severity and outcome. In addition, comparison to rotational TBI model revealed distinctive temporal pattern of serum biomarker expression dependent on the type of injury.
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