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- Risling, M, et al.
(author)
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Differential acute gene expression changes after 5 types of traumatic injury in spinal cord and the brain
- 2010
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In: 40th Neuroscience Conference, November 13-17, 2010, San Diego, USA. ; , s. Program 467.16, Poster AA16-
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Conference paper (other academic/artistic)abstract
- Although a general poor outcome of lesions in mammalian central nervous system there are some interesting regional differences in the response to traumatic injury. There are indications that the inflammatory pattern and the duration of traumatic defects in the Blood Brain Barrier are dissimilar in the brain and the spinal cord. In this study we have examined the acute gene expression response in the adult rat after two types of traumatic brain injury (TBI) and two types of lesions affecting the spinal cord. The TBI models were an exposure to blast overpressure (200 kPa), a sagittal acceleration injury and a cortical penetration injury. The spinal injuries were lumbar ventral root avulsion at the border between the CNS and PNS. Ventral root avulsion is not followed by spontaneous regrowth. The second spinal injury was replantation of avulsed spinal ventral roots, enabling significant and useful regrowth of motor axons. In this study we have analyzed the acute response to these 5 types of injury with gene arrays combined with cluster analysis of gene ontology search terms. 3 adult Sprague-Dawley rats for each of the 5 models were used. 24 h after the injury, the animals were anesthetized and the inferior vena cava was cut open. The hippocampus and the cortex were used for analysis of the 3 TBI models and the ipsilateral ventral quadrat of the affected spinal cord segment was used for the spinal injuries. RNA samples were analysed was then hybridized to Affymetrix Rat Gene ST 1.0 array. The data show significant differences between rats subjected to ventral replantation compared to avulsion only. Whereas, the number of genes related to cell death is similar in the two models after 24 hours, we observed a significantly larger number of genes related to neurite growth and development in the rats treated with ventral root replantation. In addition, an acute inflammatory response was observed after avulsion, while effects on genes related to synaptic transmission were much more pronounced after replantation than after avulsion without replantation. Blast overpressure induced limited shifts in gene expression in the hippocampus. The most interesting findings were a down regulation of genes involved in neurogenesis and synaptic transmission. Acceleration and penetration injuries resulted in changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus and the cortex. We, conclude that cluster analysis of gene ontology search terms analysis may facilitate the comparison of the acute response in different types of injury.
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- Risling, M, et al.
(author)
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Differential gene expression changes for complement C1q and C3 after injuries to dorsal and ventral nerve roots
- 2011
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In: 41st Neuroscience Conference, Washington, DC.
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Conference paper (other academic/artistic)abstract
- C1q is an initiating protein in the classical complement cascade and is a key element in the inflammatory response to injuries in the nervous system. Interestingly, it has been shown to be expressed by immature neurons and is localized to synapses. Mice that are deficient to C1q or the downstream complement factor C3 show severe defects in elimination of synapses during development (Stevens et al., 2007). This can lead to nonappropriate connections, increased excitatory connectivity and epileptiform activity. Recent in vitro studies indicate that C1q can directly promote neuronal survival (Benoit and Tenner, 2011). In this study we have examined expression changes after injuries to dorsal and ventral roots in 18 adult rats using Affymetrix Rat Gene ST 1.0 arrays.The data suggest that the cute response in genes for complement factors C1q and C3 is different after different nerve root lesions. The ventral root replantation and nerve injuries are followed by a regenerative response while dorsal root transection and ventral root avulsion are examples of non-regenerative conditions.
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- Fried, K., et al.
(author)
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Expression of ErbB3, ErbB4, and neuregulin-1 mRNA during tooth development
- 2002
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In: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 224:3, s. 356-360
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Journal article (peer-reviewed)abstract
- The receptor tyrosine kinases ErbB3 and ErbB4, which bind to various variants of neuregulin (NRG), play fundamental roles in neural development and in organs, which form through epithelial-mesenchymal interactions. Here, we demonstrate that NRG-1 and the receptors ErbB3 and ErbB4 are expressed locally during rodent tooth development. However, the mRNA expression patterns of ErbB3 and ErbB4 were distinctly different during odontogenesis. Examinations of teeth in genetically heart-rescued ErbB4-/- mice did not reveal any obvious deviation from the normal phenotype. The results suggest that ErbB3 and ErbB4 may participate in tooth morphogenesis. The specific interactions between NRG isoforms and ErbB receptors during this process remain to be determined.
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- Funakoshi, H, et al.
(author)
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Targeted expression of a multifunctional chimeric neurotrophin in the lesioned sciatic nerve accelerates regeneration of sensory and motor axons
- 1998
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 95:9, s. 5269-5274
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Journal article (peer-reviewed)abstract
- Peripheral nerve injury markedly regulates expression of neurotrophins and their receptors in the lesioned nerve. However, the role of endogenously produced neurotrophins in the process of nerve regeneration is unclear. Expression of a multifunctional neurotrophin, pan-neurotrophin-1 (PNT-1), was targeted to the peripheral nerves of transgenic mice by using a gene promoter that is specifically activated after nerve lesion but that is otherwise silent in all other tissues and during development. PNT-1 is a chimeric neurotrophin that combines the active sites of the neurotrophins nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 and binds and activates all known neurotrophin receptors. In adult transgenic mice, PNT-1 was highly expressed in transected but not in intact sciatic nerve. Morphometric analyses at the electron microscopy level showed increased and accelerated recovery of axon diameter of myelinated fibers in crushed peripheral nerves of transgenic mice compared with wild type. Examination of nerve bundles in target tissues indicated accelerated reinnervation of foot pad dermis and flexor plantaris muscle in transgenic mice. Moreover, transected sensory and motor axons of transgenic mice showed faster and increased return of neurophysiological responses, suggesting an accelerated rate of axonal elongation. Importantly, transgenic mice also showed a markedly ameliorated loss of skeletal muscle weight, indicating functional regeneration of motor axons. Together, these data provide evidence, at both the anatomical and functional levels, that neurotrophins endogenously produced by the lesioned nerve are capable of significantly accelerating the regeneration of both sensory and motor axons after peripheral nerve damage. In addition, our results indicate that exogenous PNT-1 administration may be an effective therapeutic treatment of peripheral nerve injuries.
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- Gunther, M, et al.
(author)
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An Experimental Model for the Study of Underwater Pressure Waves on the Central Nervous System in Rodents: A Feasibility Study
- 2022
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In: Annals of biomedical engineering. - : Springer Science and Business Media LLC. - 1573-9686 .- 0090-6964. ; 50:1, s. 78-85
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Journal article (peer-reviewed)abstract
- Underwater blast differs from blast in air. The increased density and viscosity of water relative to air cause injuries to occur almost exclusively as primary blast, and may cause disorientation in a diver, which may lead to inability to protect the airway and cause drowning. However, cognitive impairments from under water blast wave exposure have not been properly investigated, and no experimental model has been described. We established an experimental model (water shock tube) for simulating the effects of underwater blast pressure waves in rodents, and to investigate neurology in relation to organ injury. The model produced standardized pressure waves (duration of the primary peak 3.5 ms, duration of the entire complex waveform including all subsequent reflections 325 ms, mean impulse 141–281 kPa-ms, mean peak pressure 91–194 kPa). 31 rats were randomized to control (n = 6), exposure 90 kPa (n = 8), 152 kPa (n = 8), and 194 kPa (n = 9). There was a linear trend between the drop height of the water shock tube and electroencephalography (EEG) changes (p = 0.014), while no differences in oxygen saturation, heart rate, S100b or macroscopic bleedings were detected. Microscopic bleedings were detected in lung, intestines, and meninges. Underwater pressure waves caused changes in EEG, at pressures when mild hemorrhage occurred in organs, suggesting an impact on brain functions. The consistent injury profile enabled for the addition of future experimental interventions.
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- Gunther, M., et al.
(author)
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Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats
- 2015
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In: Journal of Clinical Neuroscience. - : Elsevier BV. - 0967-5868 .- 1532-2653. ; 22:9, s. 1477-1483
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Journal article (peer-reviewed)abstract
- We examined the effects of N-acetylcysteine amide (NACA) in the secondary inflammatory response following a novel method of focal penetrating traumatic brain injury (TBI) in rats. N-acetylcysteine (NAC) has limited but well-documented neuroprotective effects after experimental central nervous system ischemia and TBI, but its bioavailability is very low. We tested NACA, a modified form of NAC with higher membrane and blood-brain barrier permeability. Focal penetrating TBI was produced in male Sprague-Dawley rats randomly selected for NACA treatment (n = 5) and no treatment (n = 5). In addition, four animals were submitted to sham surgery. After 2 hours or 24 hours the brains were removed, fresh frozen, cut in 14 mu m coronal sections and subjected to immunohistochemistry, immunofluorescence, Fluoro-Jade and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses. All treated animals were given 300 mg/kg NACA intraperitoneally (IP) 2 minutes post trauma. The 24 hour survival group was given an additional bolus of 300 mg/kg IF after 4 hours. NACA treatment decreased neuronal degeneration by Fluoro-Jade at 24 hours with a mean change of 35.0% (p
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