Publications by authors named "Caroline L van Heijningen"

6 Publications

  • Page 1 of 1

Remote Corticospinal Tract Degeneration After Cortical Stroke in Rats May Not Preclude Spontaneous Sensorimotor Recovery.

Neurorehabil Neural Repair 2021 Sep 21:15459683211041318. Epub 2021 Sep 21.

Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.

Recovery of motor function after stroke appears to be related to the integrity of axonal connections in the corticospinal tract (CST) and corpus callosum, which may both be affected after cortical stroke. In the present study, we aimed to elucidate the relationship of changes in measures of the CST and transcallosal tract integrity, with the interhemispheric functional connectivity and sensorimotor performance after experimental cortical stroke. We conducted in vivo diffusion magnetic resonance imaging (MRI), resting-state functional MRI, and behavior testing in twenty-five male Sprague Dawley rats recovering from unilateral photothrombotic stroke in the sensorimotor cortex. Twenty-three healthy rats served as controls. A reduction in the number of reconstructed fibers, a lower fractional anisotropy, and higher radial diffusivity in the ipsilesional but intact CST, reflected remote white matter degeneration. In contrast, transcallosal tract integrity remained preserved. Functional connectivity between the ipsi- and contralesional forelimb regions of the primary somatosensory cortex significantly reduced at week 8 post-stroke. Comparably, usage of the stroke-affected forelimb was normal at week 28, following significant initial impairment between day 1 and week 8 post-stroke. Our study shows that post-stroke motor recovery is possible despite degeneration in the CST and may be supported by intact neuronal communication between hemispheres.
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http://dx.doi.org/10.1177/15459683211041318DOI Listing
September 2021

Biomolecular changes and subsequent time-dependent recovery in hippocampal tissue after experimental mild traumatic brain injury.

Sci Rep 2021 Jun 14;11(1):12468. Epub 2021 Jun 14.

Department of Biophysics, Faculty of Medicine, Altinbas University, Bakirkoy, Istanbul, Turkey.

Traumatic brain injury (TBI) is the main cause of disability and mortality in individuals under the age of 45 years. Elucidation of the molecular and structural alterations in brain tissue due to TBI is crucial to understand secondary and long-term effects after traumatic brain injury, and to develop and apply the correct therapies. In the current study, the molecular effects of TBI were investigated in rat brain at 24 h and 1 month after the injury to determine acute and chronic effects, respectively by Fourier transform infrared imaging. This study reports the time-dependent contextual and structural effects of TBI on hippocampal brain tissue. A mild form of TBI was induced in 11-week old male Sprague Dawley rats by weight drop. Band area and intensity ratios, band frequency and bandwidth values of specific spectral bands showed that TBI causes significant structural and contextual global changes including decrease in carbonyl content, unsaturated lipid content, lipid acyl chain length, membrane lipid order, total protein content, lipid/protein ratio, besides increase in membrane fluidity with an altered protein secondary structure and metabolic activity in hippocampus 24 h after injury. However, improvement and/or recovery effects in these parameters were observed at one month after TBI.
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http://dx.doi.org/10.1038/s41598-021-92015-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203626PMC
June 2021

Translational Value of Skilled Reaching Assessment in Clinical and Preclinical Studies on Motor Recovery After Stroke.

Neurorehabil Neural Repair 2021 05 7;35(5):457-467. Epub 2021 Apr 7.

University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Background: Assessment of skilled reaching enables extensive analysis of upper limb function in clinical and preclinical studies on poststroke outcome. However, translational research if often limited by lack of correspondence between tests of human and rodent motor function.

Objectives: To determine (1) the translational value of skilled reaching performance for preclinical research by comparing the behavioral recovery profiles of skilled reaching characteristics between humans and rats recovering from stroke and (2) the relationship between skilled reaching performance and commonly used clinical outcome measures after stroke.

Methods: Twelve patients with ischemic or hemorrhagic stroke and 17 rats with photothrombotic stroke underwent an equivalent skilled reaching test at different time points, representing early to late subacute stages poststroke. Success scores and a movement element rating scale were used to measure the skilled reaching performance. The Fugl-Meyer Upper Extremity (FM-UE) assessment and the Action Research Arm Test (ARAT) were used as clinical outcome measures.

Results: Both species had muscle flaccidity at the early subacute stage after stroke and showed motor recovery following a proximal-distal principle toward the early subacute stage, albeit for rats within a shorter time course. Human skilled reaching scores and FM-UE and ARAT scores in the first 3 months poststroke were significantly correlated ( < .05).

Conclusions: Our study demonstrates that poststroke changes in skilled reaching performance are highly similar between rats and humans and correspond with standard clinical outcome measures. Skilled reaching testing therefore offers an effective and highly translational means for assessment of motor recovery in experimental and clinical stroke settings.
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http://dx.doi.org/10.1177/15459683211005022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127668PMC
May 2021

Activation response and functional connectivity change in rat cortex after bilateral transcranial direct current stimulation-An exploratory study.

J Neurosci Res 2021 May 28;99(5):1377-1389. Epub 2021 Jan 28.

Biomedical Magnetic Resonance Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique implicated as a promising adjunct therapy to improve motor function through the neuromodulation of brain networks. Particularly bilateral tDCS, which affects both hemispheres, may yield stronger effects on motor learning than unilateral stimulation. Therefore, the aim of this exploratory study was to develop an experimental model for simultaneous magnetic resonance imaging (MRI) and bilateral tDCS in rats, to measure instant and resultant effects of tDCS on network activity and connectivity. Naïve, male Sprague-Dawley rats were divided into a tDCS (n = 7) and sham stimulation group (n = 6). Functional MRI data were collected during concurrent bilateral tDCS over the sensorimotor cortex, while resting-state functional MRI and perfusion MRI were acquired directly before and after stimulation. Bilateral tDCS induced a hemodynamic activation response, reflected by a bilateral increase in blood oxygenation level-dependent signal in different cortical areas, including the sensorimotor regions. Resting-state functional connectivity within the cortical sensorimotor network decreased after a first stimulation session but increased after a second session, suggesting an interaction between multiple tDCS sessions. Perfusion MRI revealed no significant changes in cerebral blood flow after tDCS. Our exploratory study demonstrates successful application of an MRI-compatible bilateral tDCS setup in an animal model. Our results indicate that bilateral tDCS can locally modulate neuronal activity and connectivity, which may underlie its therapeutic potential.
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http://dx.doi.org/10.1002/jnr.24793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048424PMC
May 2021

Imaging Markers for the Characterization of Gray and White Matter Changes from Acute to Chronic Stages after Experimental Traumatic Brain Injury.

J Neurotrauma 2021 Jun 11;38(12):1642-1653. Epub 2021 Jan 11.

Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands. ORCID ID: 0000-0002-8185-9209; 0000-0002-4623-4078.

Despite clinical symptoms, a large majority of people with mild traumatic brain injury (TBI) have normal computed tomography (CT) and magnetic resonance imaging (MRI) scans. Therefore, present-day neuroimaging tools are insufficient to diagnose or classify low grades of TBI. Advanced neuroimaging techniques, such as diffusion-weighted and functional MRI, may yield novel biomarkers that may aid in the diagnosis of TBI. Therefore, the present study had two aims: first, to characterize the development of MRI-based measures of structural and functional changes in gray and white matter regions from acute to chronic stages after mild and moderate TBI; and second, to identify the imaging markers that can most accurately predict outcome after TBI. To these aims, 52 rats underwent serial functional (resting-state) and structural (T1-, T2-, and diffusion-weighted) MRI before and 1 h, 1 day, 1 week, 1 month and 3-4 months after mild or moderate experimental TBI. All rats underwent behavioral testing. Histology was performed in subgroups of rats at different time points. Early after moderate TBI, axial and radial diffusivities were increased, and fractional anisotropy was reduced in the corpus callosum and bilateral hippocampi, which normalized over time and was paralleled by recovery of sensorimotor function. Correspondingly, histology revealed decreased myelin staining early after TBI, which was not detected at chronic stages. No significant changes in individual outcome measures were detected after mild TBI. However, multivariate analysis showed a significant additive contribution of diffusion parameters in the distinction between control and different grades of TBI-affected brains. Therefore, combining multiple imaging markers may increase the sensitivity for TBI-related pathology.
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http://dx.doi.org/10.1089/neu.2020.7151DOI Listing
June 2021

Selective parasympathetic innervation of subcutaneous and intra-abdominal fat--functional implications.

J Clin Invest 2002 Nov;110(9):1243-50

Netherlands Institute for Brain Research, Amsterdam, The Netherlands.

The wealth of clinical epidemiological data on the association between intra-abdominal fat accumulation and morbidity sharply contrasts with the paucity of knowledge about the determinants of fat distribution, which cannot be explained merely in terms of humoral factors. If it comes to neuronal control, until now, adipose tissue was reported to be innervated by the sympathetic nervous system only, known for its catabolic effect. We hypothesized the presence of a parasympathetic input stimulating anabolic processes in adipose tissue. Intra-abdominal fat pads in rats were first sympathetically denervated and then injected with the retrograde transneuronal tracer pseudorabies virus (PRV). The resulting labeling of PRV in the vagal motor nuclei of the brain stem reveals that adipose tissue receives vagal input. Next, we assessed the physiological impact of these findings by combining a fat pad-specific vagotomy with a hyperinsulinemic euglycemic clamp and RT-PCR analysis. Insulin-mediated glucose and FFA uptake were reduced by 33% and 36%, respectively, whereas the activity of the catabolic enzyme hormone-sensitive lipase increased by 51%. Moreover, expression of resistin and leptin mRNA decreased, whereas adiponectin mRNA did not change. All these data indicate an anabolic role for the vagal input to adipose tissue. Finally, we demonstrate somatotopy within the central part of the autonomic nervous system, as intra-abdominal and subcutaneous fat pads appeared to be innervated by separate sympathetic and parasympathetic motor neurons. In conclusion, parasympathetic input to adipose tissue clearly modulates its insulin sensitivity and glucose and FFA metabolism in an anabolic way. The implications of these findings for the (patho)physiology of fat distribution are discussed.
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http://dx.doi.org/10.1172/JCI15736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151610PMC
November 2002
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