| 1. |
- Axelson, Hans, 1965-, et al.
(författare)
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Plasticity of the contralateral motor cortex following focal traumatic brain injury in the rat
- 2013
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 31:1, s. 73-85
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Recovery is limited following traumatic brain injury (TBI) since injured axons regenerate poorly and replacement of lost cells is minimal. Behavioral improvements could instead be due to plasticity of uninjured brain regions. We hypothesized that plasticity of the uninjured hemisphere occurs contralateral to a focal TBI in the adult rat. Thus, we performed cortical mapping of the cortex contralateral to the TBI using intracortical microstimulation (ICMS). Methods: A focal TBI was induced using the weight-drop technique (n = 5) and sham-injured animals were used as controls (n = 4). At five weeks post-injury, ICMS was used to map the motor area contralateral to the injury. Motor responses were detected by visual inspection and electromyography (EMG). Results: In sham- and brain-injured animals, numerous fore- and hindlimb motor responses contralateral to the stimulation (ipsilateral to the injury) were obtained. Compared to sham-injured controls, there was a markedly increased (p < 0.05) number of fore- and hindlimb responses ipsilateral to the stimulation after TBI. Conclusion: Following focal TBI in the rat, our data suggest reorganization of cortical and/or subcortical regions in the uninjured hemisphere contralateral to a focal TBI leading to an altered responsiveness to ICMS. Although we cannot exclude that these changes are maladaptive, it is plausible that this plasticity process positively influences motor recovery after TBI.
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| 2. |
- Bunketorp Käll, Lina, 1975, et al.
(författare)
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Adaptive motor cortex plasticity following grip reconstruction in individuals with tetraplegia
- 2018
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Ingår i: Restorative Neurology and Neuroscience. - : IOS Press. - 0922-6028 .- 1878-3627. ; 36:1, s. 73-82
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tendon transfer is a surgical technique for restoring upper limb motor control in patients with cervical spinal cord injuries (SCI), and offers a rare window into cortical neuroplasticity following regained arm and hand function. Objective: Here, we aimed to examine neuroplasticity mechanisms related to re-established voluntary motor control of thumb flexion following tendon transfer. Methods: We used functional Magnetic Resonance Imaging (fMRI) to test the hypothesis that restored limb control following tendon transfer is mediated by activation of that limb's area of the primary motor cortex. We examined six individuals with tetraplegia who underwent right-sided surgical grip reconstruction at Sahlgrenska University Hospital, Sweden. All were right-handed males, with a SCI at the C6 or C7 level, and a mean age of 40 years (range = 31-48). The average number of years elapsed since the SCI was 13 (range = 6-26). Six right-handed gender-and age-matched control subjects were included (mean age 39 years, range = 29-46). Restoration of active thumb flexion in patients was achieved by surgical transfer of one of the functioning elbow flexors (brachioradialis), to the paralyzed thumb flexor (flexor pollicis longus). We studied fMRI responses to isometric right-sided elbow flexion and key pinch, and examined the cortical representations within the left hemisphere somatomotor cortex a minimum of one year after surgery. Results: Cortical activations elicited by elbow flexion did not differ in topography between patients and control participants. However, in contrast to control participants, patients' cortical thumb flexion activations were not topographically distinct from their elbow flexion activations. Conclusion: This result speaks against a topographic reorganization in which the thumb region regains thumb control following surgical tendon transfer. Instead, our findings suggest a neuroplastic mechanism in which motor cortex resources previously dedicated to elbow flexion adapt to control the thumb.
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| 3. |
- Bunketorp Käll, Lina, 1975, et al.
(författare)
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Feasibility of using fNIRS to explore motor-related regional haemodynamic signal changes in patients with sensorimotor impairment and healthy controls: A pilot study
- 2023
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 41:3-4, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- Background: While functional near-infrared spectroscopy (fNIRS) can provide insight into cortical brain activity during motor tasks in healthy and diseased populations, the feasibility of using fNIRS to assess haemoglobin-evoked responses to reanimated upper limb motor function in patients with tetraplegia remains unknown. Objective: The primary objective of this pilot study is to determine the feasibility of using fNIRS to assess cortical signal intensity changes during upper limb motor tasks in individuals with surgically restored grip functions. The secondary objectives are: 1) to collect pilot data on individuals with tetraplegia to determine any trends in the cortical signal intensity changes as measured by fNIRS and 2) to compare cortical signal intensity changes in affected individuals versus age-appropriate healthy volunteers. Specifically, patients presented with tetraplegia, a type of paralysis resulting from a cervical spinal cord injury causing loss of movement and sensation in both lower and upper limbs. All patients have their grip functions restored by surgical tendon transfer, a procedure which constitutes a unique, focused stimulus for brain plasticity. Method: fNIRS is used to assess changes in cortical signal intensity during the performance of two motor tasks (isometric elbow and thumb flexion). Six individuals with tetraplegia and six healthy controls participate in the study. A block paradigm is utilized to assess contralateral and ipsilateral haemodynamic responses in the premotor cortex (PMC) and primary motor cortex (M1). We assess the amplitude of the optical signal and spatial features during the paradigms. The accuracy of channel locations is maximized through 3D digitizations of channel locations and co-registering these locations to template atlas brains. A general linear model approach, with short-separation regression, is used to extract haemodynamic response functions at the individual and group levels. Results: Peak oxyhaemoglobin (oxy-Hb) changes in PMC appear to be particularly bilateral in nature in the tetraplegia group during both pinch and elbow trials whereas for controls, a bilateral PMC response is not especially evident. In M1 / primary sensory cortex (S1), the oxy-Hb responses to the pinch task are mainly contralateral in both groups, while for the elbow flexion task, lateralization is not particularly clear. Conclusions: This pilot study shows that the experimental setup is feasible for assessing brain activation using fNIRS during volitional upper limb motor tasks in individuals with surgically restored grip functions. Cortical signal changes in brain regions associated with upper extremity sensorimotor processing appear to be larger and more bilateral in nature in the tetraplegia group than in the control group. The bilateral hemispheric response in the tetraplegia group may reflect a signature of adaptive brain plasticity mechanisms. Larger studies than this one are needed to confirm these findings and draw reliable conclusions.
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| 4. |
- Conte, Valeria, et al.
(författare)
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TrkB gene transfer does not alter hippocampal neuronal loss and cognitive deficits following traumatic brain injury in mice
- 2008
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 26:1, s. 45-56
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The ability of brain-derived neurotrophic factor (BDNF) to attenuate secondary damage and influence behavioral outcome after experimental traumatic brain injury (TBI) remains controversial. Because TBI can result in decreased expression of the trkB receptor, thereby preventing BDNF from exerting potential neuroprotective effects, the contribution of both BDNF and its receptor trkB to hippocampal neuronal loss and cognitive dysfunction were evaluated. METHODS: Full-length trkB was overexpressed in the left hippocampus of adult C57Bl/6 mice using recombinant adeno-associated virus serotype 2/5 (rAAV 2/5). EGFP (enhanced green fluorescent protein) expression was present at two weeks after AAV-EGFP injection and remained sustained up to four weeks after the injection. At 2 weeks following gene transduction, mice were subjected to parasagittal controlled cortical impact (CCI) brain injury, followed by either BDNF or PBS infusion into the hippocampus. RESULTS: No differences were observed in learning ability at two weeks post-injury or in motor function from 48 hours to two weeks among treatment groups. The number of surviving pyramidal neurons in the CA2-CA3 region of the hippocampus was also not different among treatment groups. CONCLUSIONS: These data suggest that neither overexpression of trkB, BNDF infusion or their combination affects neuronal survival or behavioral outcome following experimental TBI in mice.
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| 5. |
- Dahlin, Erika, 1981-, et al.
(författare)
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Training of the executive component of working memory : subcortial areas mediate transfer effects
- 2009
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Ingår i: Restorative Neurology and Neuroscience. - : IOS Press. - 0922-6028 .- 1878-3627. ; 27:5, s. 405-419
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Several recent studies show that training can improve working memory (WM) performance. In this review, many issues related to WM training, such as neural basis, transfer effects, and age-related changes are addressed. Method: We focus on our own studies investigating training on tasks taxing the executive updating function and discuss our findings in relation to results from other studies investigating training of the executive component of WM. Results: The review confirms positive behavioral effects of training on working memory. The most common neural pattern following training is fronto-parietal activity decreases. Increases in sub-cortical areas are also frequently reported after training, and we suggest that such increases indicate changes in the underlying skill following training. Transfer effects are in general difficult to demonstrate. Some studies show that older adults increase their performance after WM training. However, transfer effects are small or nonexistent in old age. Conclusions: The main finding in this review is that sub-cortical areas seem to have a critical role in mediating transfer effects to untrained tasks after at least some forms of working memory training (such as updating).
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| 6. |
- Ekmark-Lewén, Sara, et al.
(författare)
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Vimentin and GFAP responses in astrocytes after contusion trauma to the murine brain
- 2010
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 28:3, s. 311-321
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Astroglial responses after traumatic brain injury are difficult to detect with routine morphological methods. The aims for this study were to compare the temporal and spatial expression pattern of vimentin-and glial fibrillary acidic protein (GFAP) in a weight drop model of mild cerebral contusion injury in the rat. We also wanted to study the vimentin response with immunohistochemistry and vimentin mRNA RT-PCR analysis in severe cortical contusion injury produced by the controlled cortical impact in the mouse. Methods: Vimentin and GFAP immunohistochemistry (1day, 3 days and 7 days) combined with vimentin mRNA RT-PCR analysis (1 h, 4 h, 22 h, 3 days and 7 days) were used after experimental traumatic brain injury in the rat and mouse. Results: Increases in post-traumatic vimentin mRNA levels in the cortex and in the hippocampus appeared together with vimentin immunoreactivity in astrocytes in the perimeter of the cortical lesion, in the subcortical white matter and in the hippocampus starting at one day after severe trauma. GFAP immunostaining revealed hypertrophic astrocytes peaking at day 3 in the perifocal cortical region. There was no significant increase in GFAP immunoreactivity in the white matter in the rat. However, in the mouse there was a slight increase in the number of GFAP positive cells in this region, 3 days after trauma. Overall the pattern of vimentin immunoreactivity was very similar in the rat and mouse. Conclusions: Vimentin immunoreactivity was more sensitive than the GFAP staining method to demonstrate the distribution and time course of astrocyte reactions after a contusion injury, especially in the white matter distant from the cortical lesion.
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| 7. |
- Flygt, Johanna, 1985-, et al.
(författare)
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Diffuse traumatic brain injury in the mouse induces a transient proliferation of oligodendrocyte progenitor cells in injured white matter tracts
- 2017
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 35:2, s. 251-263
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Tidskriftsartikel (refereegranskat)abstract
- Background: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI.Objective: We hypothesized that central fluid percussion injury (cFPI) in mice, a TBI model causing wide-spread axonal injury, results in OPC proliferation.Methods: Proliferation of OPCs was evaluated in 27 cFPI mice using 5-ethynyl-2-deoxyuridine (EdU) labeling and a cell proliferation assay at 2 (n=9), 7 (n = 8) and 21 (n = 10) days post injury (dpi). Sham-injured mice (n = 14) were used as controls. OPC proliferation was quantified by immunohistochemistry using the OPC markers NG2 and Olig2 in several white matter loci including the corpus callosum, external capsule, fimbriae, the internal capsule and cerebral peduncle.Results: The number of EdU/DAPI/Olig2-positive cells were increased in the cFPI group compared to sham-injured animals at 7 days post-injury (dpi; p≤0.05) in the majority of white matter regions. The OPC proliferation had subsided by 21 dpi. The number of EdU/DAPI/NG2 cells was also increase at 7 dpi in the external capsule and fimbriae.Conclusion: These results suggest that traumatic axonal injury in the mouse induces a transient proliferative response of residing OPCs. These proliferating OPCs may replace dead oligodendrocytes and contribute to remyelination, which needs evaluation in future studies.
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| 8. |
- Gunther, Mattias, et al.
(författare)
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Temporal gene expression changes after acute and delayed ventral root avulsion-reimplantation
- 2020
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Ingår i: Restorative Neurology and Neuroscience. - : IOS PRESS. - 0922-6028 .- 1878-3627. ; 38:1, s. 23-40
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a model of injured spinal motor neurons where the avulsed spinal nerve is surgically reimplanted, useful regrowth of the injured nerve follows, both in animal experiments and clinical cases. This has led to surgical reimplantation strategies with subsequent partial functional motoric recovery. Still, the ideal time point for successful regeneration after reimplantation and the specific genetic profile of this time point is not known. Objective: To explore the temporal gene expression of the whole genome in the ventral spinal cord after reimplantation at different time points after avulsion. Methods: Totally 18 adult rats were subjected to avulsion of the left L5 root only (N = 3), avulsion followed by acute spinal reimplantation (N = 3), avulsion followed by 24 h (N = 3) or 48 h (N = 3) delayed reimplantation Animals were allowed to survive 24 h after their respective surgery whereafter the ventral quadrant of the spinal cord at the operated side was harvested, processed for and analysed with Affymetrix Rat Gene ST 1.0 array followed by statistical analysis of gene expression patterns Results: Specific gene expression patterns were found at different time points after avulsion and reimplantation. Over all, early reimplantation seemed to diminish inflammatory response and support gene regulation related to neuronal activity compared to avulsion only or delayed reimplantation. In addition did gene activity after avulsion-reimplantation correspond to regeneration-associated genes typical for regeneration in the peripheral nervous system. Conclusions: Our study reveal that genetic profiling after this kind of injury is possible, that specific and distinct expression patterns can be found with early reimplantation being favourable over late and that regenerative activity in this kind of injury bears hallmark typical for peripheral nerve regeneration. These findings can be useful in elucidating specific genetic expression typical for successful nerve regeneration, hopefully not only in this specific model but in the nervous system in general.
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| 9. |
- Israelsson, Charlotte, et al.
(författare)
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Altered expression of myelin-associated inhibitors and their receptors after traumatic brain injury in the mouse
- 2014
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 32:5, s. 717-731
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: When central nervous system axons are injured, regeneration is partly inhibited by myelin-associated inhibitors (MAIs). Following traumatic brain injury (TBI) in the rat, pharmacological neutralisation of the MAIs Nogo-A and myelin-associated glycoprotein (MAG) resulted in improved functional outcome. In contrast, genetic or pharmacological neutralization of the MAI receptors Nogo-66 receptor 1 (NgR1) or paired-immunoglobulin like receptor-B (PirB) showed an unaltered or impaired outcome following TBI in mice. The aim of the present study was thus to evaluate the MAI expression levels following TBI in mice. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure total RNA isolated from brains of young adult male C57BL/6 mice at one, three or seven days following controlled cortical impact TBI or sham injury. Hippocampal and neocortical tissue ipsi- and contralateral to the injury was analyzed for Nogo-A, oligodendrocyte-myelin glycoprotein (OMgp), MAG, and the MAI receptors PirB and NgR1, including its co-receptor Lingo1. Results: Compared to sham-injured controls, PirB neocortical expression was significantly upregulated at one day and NgR1 expression downregulated at seven days post-TBI. In the hippocampus, transcriptional upregulation was observed in Nogo-A (one day post-injury), MAG and PirB at seven days post-injury. In contrast, the hippocampal transcripts of NgR1 and Lingo1 were decreased at seven days post-injury. The expression of OMgp was unaltered at all time points post-injury. Conclusion: These results suggest that early dynamic changes in MAI gene expression occur following TBI in the mouse, particularly in the hippocampus, which may play an inhibitory role for post-injury regeneration and plasticity.
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| 10. |
- Kononenko, Olga, et al.
(författare)
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Focal traumatic brain injury induces neuroplastic molecular responses in lumbar spinal cord
- 2019
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Ingår i: Restorative Neurology and Neuroscience. - : IOS PRESS. - 0922-6028 .- 1878-3627. ; 37:2, s. 87-96
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objectives: Motor impairment induced by traumatic brain injury (TBI) may be mediated through changes in spinal molecular systems regulating neuronal plasticity. We assessed whether a focal controlled cortical impact (CCI) TBI in the rat alters expression of the Tgfb1, c-Fos, Bdnf and Gap43 neuroplasticity genes in lumbar spinal cord.Approach/Methods: Adult male Sprague-Dawley rats (n = 8) were subjected to a right-side CCI over the anterior sensorimotor hindlimb representation area or sham-injury (n=8). Absolute expression levels of Tgfb1, c-Fos, Bdnf, and Gapd43 genes were measured by droplet digital PCR in ipsi- and contralesional, dorsal and ventral quadrants of the L4 and L5 spinal cord. The neuronal activity marker c-Fos was analysed by immunohistochemistry in the dorsal L4 and L5 segments. The contra- vs. ipsilesional expression pattern was examined as the asymmetry index, AI.Results: The Tgfb1 mRNA levels were significantly higher in the CCI vs. sham-injured rats, and in the contra- vs. ipsilesional dorsal domains in the CCI group. The number of c-Fos-positive cells was elevated in the L4 and L5 segments; and on the contralesional compared to the ipsilesional side in the CCI group. The c-Fos AI in the dorsal laminae was significantly increased by CCI.Conclusions: The results support the hypothesis that focal TBI induces plastic alterations in the lumbar spinal cord that may contribute to either motor recovery or maladaptive motor responses.
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