Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be a grey matter pathology, a growing body of evidence links this disease with white matter abnormalities. In this study, we explore the impact of TLE onset and progression in the immature brain on white matter integrity and development utilising the rat model of Li-pilocarpine-induced TLE at the 12th postnatal day (P). Diffusion tensor imaging (DTI) and Black-Gold II histology uncovered disruptions in major white matter tracks (corpus callosum, internal and external capsules, and deep cerebral white matter) spreading through the whole brain at P28. These abnormalities were mostly not present any longer at three months after TLE induction, with only limited abnormalities detectable in the external capsule and deep cerebral white matter. Relaxation Along a Fictitious Field in the rotating frame of rank 4 indicated that white matter changes observed at both timepoints, P28 and P72, are consistent with decreased myelin content. The animals affected by TLE-induced white matter abnormalities exhibited increased functional connectivity between the thalamus and medial prefrontal and somatosensory cortex in adulthood. Furthermore, histological analyses of additional animal groups at P15 and P18 showed only mild changes in white matter integrity, suggesting a gradual age-dependent impact of TLE progression. Taken together, TLE progression in the immature brain distorts white matter development with a peak around postnatal day 28, followed by substantial recovery in adulthood. This developmental delay might give rise to cognitive and behavioural comorbidities typical for early-onset TLE.
- MeSH
- bílá hmota * diagnostické zobrazování patologie MeSH
- dospělí MeSH
- epilepsie temporálního laloku * patologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myelinová pochva patologie MeSH
- předškolní dítě MeSH
- status epilepticus * chemicky indukované patologie MeSH
- zobrazování difuzních tenzorů MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- předškolní dítě MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
[This corrects the article DOI: 10.3389/fnins.2021.625167.].
- Publikační typ
- tisková chyba MeSH
Epidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI). The method achieves orientation selectivity by controlling the main direction of the electric field gradients using individually driven channels. Here, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. The fMRI activation patterns during spinal cord stimulation demonstrated the complexity of brain networks stimulated by OS-ESCS paradigms, involving brain areas responsible for the transmission of the motor and sensory information. The OS approach may allow targeting ESCS to spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation.
- MeSH
- epidurální prostor diagnostické zobrazování patofyziologie MeSH
- implantované elektrody MeSH
- krysa rodu rattus MeSH
- magnetická rezonanční tomografie * MeSH
- míšní stimulace * MeSH
- poranění míchy * diagnostické zobrazování patofyziologie terapie MeSH
- potkani Sprague-Dawley MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Remyelination is a naturally occurring response to demyelination and has a central role in the pathophysiology of multiple sclerosis and traumatic brain injury. Recently we demonstrated that a novel MRI technique entitled Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) achieved exceptional sensitivity in detecting the demyelination processes induced by lysophosphatidylcholine (LPC) in rat brain. In the present work, our aim was to test whether RAFF4, along with magnetization transfer (MT) and diffusion tensor imaging (DTI), would be capable of detecting the changes in the myelin content and microstructure caused by modifications of myelin sheets around axons or by gliosis during the remyelination phase after LPC-induced demyelination in the corpus callosum of rats. We collected MRI data with RAFF4, MT and DTI at 3 days after injection (demyelination stage) and at 38 days after injection (remyelination stage) of LPC (n = 12) or vehicle (n = 9). Cell density and myelin content were assessed by histology. All MRI metrics detected differences between LPC-injected and control groups of animals in the demyelination stage, on day 3. In the remyelination phase (day 38), RAFF4, MT parameters, fractional anisotropy, and axial diffusivity detected signs of a partial recovery consistent with the remyelination evident in histology. Radial diffusivity had undergone a further increase from day 3 to 38 and mean diffusivity revealed a complete recovery correlating with the histological assessment of cell density attributed to gliosis. The combination of RAFF4, MT and DTI has the potential to differentiate between normal, demyelinated and remyelinated axons and gliosis and thus it may be able to provide a more detailed assessment of white matter pathologies in several neurological diseases.
- Publikační typ
- časopisecké články MeSH
Previous studies that focused on treating major depressive disorder with conventional deep brain stimulation (DBS) paradigms produced inconsistent results. In this proof-of-concept preclinical study in rats (n = 8), we used novel paradigms of orientation selective DBS for stimulating the complex circuitry crossing the infralimbic cortex, an area considered analogous to human subgenual cingulate cortex. Using functional MRI at 9.4 T, we monitored whole brain responses to varying the electrical field orientation of DBS within the infralimbic cortex. Substantial alterations of functional MRI responses in the amygdala, a major node connected to the infralimbic cortex implicated in the pathophysiology of depression, were observed. As expected, the activation cluster near the electrode was insensitive to the changes of the stimulation orientation. Hence, our findings substantiate the ability of orientation selective stimulation (OSS) to recruit neuronal pathways of distinct orientations relative to the position of the electrode, even in complex circuits such as those involved in major depressive disorder. We conclude that OSS is a promising approach for stimulating brain areas that inherently require individualisation of the treatment approach.
- Publikační typ
- časopisecké články MeSH
