Changes In Neural Tissue Research Articles

Gray matter volume of the feline cerebral cortex and structural plasticity following perinatal deafness

In response to sensory deprivation, the brain adapts according to contemporary demands to efficiently navigate a modified perceptual environment. This reorganization may result in improved processing of the remaining senses–a phenomenon referred to as compensatory crossmodal plasticity. One approach to explore this neuroplasticity is to consider the macrostructural changes in neural tissue that mirror this functional optimization. The current study is the first of its kind to measure MRI-derived gray matter (GM) volumes of control felines (n=30), while additionally identifying volumetric differences in response to perinatal deafness (30 ototoxically-deafened cats). To accomplish this purpose, regional and morphometric methods were performed in parallel. The regional analysis evaluated volumetric alterations of global GM, as well as the volumes of 146 regions of interest (ROIs) and 12 functional subgroupings of these ROIs. Results revealed whole-brain GM preservation; however, somatosensory and visual cortices exhibited an overall increase in volume. On a smaller scale, this analysis uncovered two auditory ROIs (second auditory cortex, A2, and ventral auditory field, VAF) that decreased in volume alongside two visual regions (anteromedial lateral suprasylvian area, AMLS and splenial visual area, SVA) that increased–all localized within the right hemisphere. Comparatively, the findings of tensor-based morphometry (TBM) generally aligned with those of the ROI-based method, as this voxel-wise approach demonstrated clusters of expansion coincident with visual- and somatosensory-related loci; although, it failed to detect any GM reductions following deafness. As distinct differences were identified in each analysis, the current study highlights the importance of employing multiple methods when exploring MRI volumetry. Overall, this study proposes that volumetric alterations within sensory loci allude to a redistribution of cortical space arising from modified perceptual demands following auditory deprivation.

Machine learning enables non-Gaussian investigation of changes to peripheral nerves related to electrical stimulation

Electrical stimulation of the peripheral nervous system (PNS) is becoming increasingly important for the therapeutic treatment of numerous disorders. Thus, as peripheral nerves are increasingly the target of electrical stimulation, it is critical to determine how, and when, electrical stimulation results in anatomical changes in neural tissue. We introduce here a convolutional neural network and support vector machines for cell segmentation and analysis of histological samples of the sciatic nerve of rats stimulated with varying current intensities. We describe the methodologies and present results that highlight the validity of the approach: machine learning enabled highly efficient nerve measurement collection, while multivariate analysis revealed notable changes to nerves’ anatomy, even when subjected to levels of stimulation thought to be safe according to the Shannon current limits.

Matrix stiffness regulates the tight junction phenotypes and local barrier properties in tricellular regions in an iPSC-derived BBB model

The blood-brain barrier (BBB) can respond to various mechanical cues such as shear stress and substrate stiffness. In the human brain, the compromised barrier function of the BBB is closely associated with a series of neurological disorders that are often also accompanied by the alteration of brain stiffness. In many types of peripheral vasculature, higher matrix stiffness decreases barrier function of endothelial cells through mechanotransduction pathways that alter cell-cell junction integrity. However, human brain endothelial cells are specialized endothelial cells that largely resist changes in cell morphology and key BBB markers. Therefore, it has remained an open question how matrix stiffness affects barrier integrity in the human BBB. To gain insight into the effects of matrix stiffness on BBB permeability, we differentiated brain microvascular endothelial-like cells from human induced pluripotent stem cells (iBMEC-like cells) and cultured the cells on extracellular matrix-coated hydrogels of varying stiffness. We first detected and quantified the junction presentation of key tight junction (TJ) proteins. Our results show matrix-dependent junction phenotypes in iBMEC-like cells, where cells on softer gels (1 kPa) have significantly lower continuous and total TJ coverages. We also determined that these softer gels also lead to decreased barrier function in a local permeability assay. Furthermore, we found that matrix stiffness regulates the local permeability of iBMEC-like cells through the balance of continuous ZO-1 TJs and no junction regions ZO-1 in tricellular regions. Together, these findings provide valuable insights into the effects of matrix stiffness on TJ phenotypes and local permeability of iBMEC-like cells. Statement of SignificanceBrain mechanical properties, including stiffness, are particularly sensitive indicators for pathophysiological changes in neural tissue. The compromised function of the blood-brain barrier is closely associated with a series of neurological disorders often accompanied by altered brain stiffness. In this study, we use polymeric biomaterials and provide new evidence that biomaterial stiffness regulates the local permeability in iPSC-derived brain endothelial cells in tricellular regions through the tight junction protein ZO-1. Our findings provide valuable insights into the changes in junction architecture and barrier permeability in response to different substrate stiffnesses. Since BBB dysfunction has been linked to many diseases, understanding the influence of substrate stiffness on junction presentations and barrier permeability could lead to the development of new treatments for diseases associated with BBB dysfunction or drug delivery across BBB systems.

A mouse model of peripheral nerve injury induced by Japanese encephalitis virus.

Japanese encephalitis virus (JEV) is the most important cause of acute encephalitis in Eastern/Southern Asia. Infection with this virus also induces peripheral nerve injury. However, the disease pathogenesis is still not completely understood. Reliable animal models are needed to investigate the molecular pathogenesis of this condition. We studied the effect of Japanese encephalitis virus infection in C57BL/6 mice after a subcutaneous challenge. Limb paralysis was determined in mice using behavioral tests, including a viral paralysis scale and the hanging wire test, as well as by changes in body weight. Nerve conduction velocity and electromyography testing indicated the presence of demyelinating neuropathy of the sciatic nerve. Pathological changes in neural tissues were examined by immunofluorescence and transmission electron microscopy, which confirmed that the predominant pathologic change was demyelination. Although Western blots confirmed the presence of the virus in neural tissue, additional studies demonstrated that an immune-induced inflammatory response resulted in severe never injury. Immunofluorescence confirmed the presence of Japanese encephalitis virus in the brains of infected mice, and an inflammatory reaction was observed with hematoxylin-eosin staining as well. However, these observations were inconsistent at the time of paralysis onset. In summary, our results demonstrated that Japanese encephalitis virus infection could cause inflammatory demyelination of the peripheral nervous system in C57BL/6 mice.

Characterisation of brain microstructural alterations in children with obstructive sleep apnea syndrome using diffusion kurtosis imaging.

Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder in children. Previous studies showed widespread alterations in white matter (WM) in children with OSA mainly by using diffusion tensor imaging (DTI), while diffusional kurtosis imaging (DKI) extended DTI and exhibited improved sensitivity in detecting developmental and pathological changes in neural tissues. Therefore, we conducted whole-brain DTI and DKI analyses and compared the differences in kurtosis and diffusion parameters within the skeleton between 41 children with OSA and 32 healthy children. Between-group differences were evaluated by tract-based spatial statistics (TBSS) analysis (p < 0.05, TFCE corrected), and partial correlations between DKI metrics and sleep parameters were assessed considering age and gender as covariates. Compared with the controls, children with OSA showed significantly decreased kurtosis fractional anisotropy (KFA) mainly in white matter regions with a complex fibre arrangement including the posterior corona radiate (PCR), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF), while decreased FA in white matter regions with a coherent fibre arrangement including the posterior limb of internal capsule (PLIC), anterior thalamic radiation (ATR), and corpus callosum (CC). Notably, the receiver operating characteristic (ROC) curve analysis demonstrated the KFA value in complex tissue regions significantly (p < 0.001) differentiated children with OSA from the controls. In addition, the KFA value in the left PCR, SLF, and IFOF showed significant partial correlations to the sleep parameters for children with OSA. Combining DKI derived kurtosis and diffusion parameters can provide complementary neuroimaging biomarkers for assessing white matter alterations, and reveal pathological changes and monitor disease progression in paediatric OSA.

The effect of Riluzole on neurological outcomes, blood-brain barrier, brain water and neuroinflammation in traumatic brain injury

BackgroundRiluzole (RLZ) is a potent anticonvulsant drug that reveals neuroprotective effects on neurological disease by inhibiting the release of glutamate and increasing its uptake. This study aims to investigate the potential neuroprotective effects of Riluzole in a rat model with acute severe traumatic brain injury (TBI). Materials and MethodsIn this study, seven groups of male Wistar rats were investigated including Sham, Intact, TBI, Saline (TBI + intraperitoneal (i.p) injection of normal saline), TBI + i.p injection of Riluzole in 2,4 and 8 mg/kg doses (RLZ 2, RLZ 4 and RLZ 8 groups), induction of severe diffuse TBI performed by weight dropping Marmarou model, and evaluation of short-term neurological deficits by using veterinary coma scale (VCS), beam-balance and beam-walk tasks. Histopathological changes in neural tissue were evaluated by using hematoxylin and eosin staining and light microscopy. Evaluation of blood-brain barrier (BBB) permeability was performed by using the Evans Blue method 6 h after traumatization. Brain water content assessment was performed by using the wet-dry method and the level of IL-1β and IL-10 was determined by using an enzyme-linked immunosorbent assay (ELISA). ResultsTreatment with Riluzole improves neurological function, VCS score, and vestibulomotor function, reduces pathological changes of neural tissue, brain edema, and level of IL-1β, and increases IL-10 concentration in CSF compared to the saline group (p < 0.0001). Treatment with 4 and 8 mg/kg of Riluzole reveals a significant therapeutic effect on consequences of TBI. This effect was enhanced by an increase in the dose of Riluzole from 4 to 8 mg/kg, but no significant changes were seen after administration of 2 mg/kg of Riluzole. ConclusionRiluzole can reduce the first and second phase of TBI damage by lowering inflammation, brain edema, histopathological destruction, BBB permeability, level of IL- 1β, and increasing IL-10 in CSF; it is highly suggested to use Riluzole in further studies and human trials, and also to consider it as a therapeutic compound in the treatment of traumatic brain injury.

Abstract P326: Vascular Risk Factors in Adulthood and Increased Diffusion Complexity of Neural Tissue Structure

Introduction: We performed a region of interest diffusion tensor imaging (DTI) and advanced diffusion complexity analysis of neural tissue to determine the impact of vascular health on novel diffusivity metrics in midlife adults. Methods: As shown in Table 1, 77 participants (26 black, 35 female) at year 30 visit in the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal study were scanned with an advanced diffusion-weighted imaging and FLAIR protocol. Fractional anisotropy (FA) and non-linear diffusion complexity, C, measures were estimated. Cumulative vascular measures were tracked from baseline up to year 30 examination. Partial correlation analyses assessed the association between cumulative vascular measures and diffusion metrics in these participants. Results: As shown in Figure 1, higher systolic blood pressure exposure was associated with increased complexity, C, (red) and decreased FA (blue). Additionally, in the white matter of black participants, who exhibited a higher cumulative vascular risk exposure, FA was lower and complexity was higher in comparison to white matter in white participants. Conclusion: Higher burden of vascular risk factor exposure from adulthood to midlife is associated with changes in the diffusion properties of neural tissue in midlife. These diffusion measures may reflect novel markers of axonal disruption, increased inflammation, and/or increased glial proliferation. These new results suggest that microstructural changes in neural tissue are sensitive to vascular health during young adulthood and are possibly therapeutic targets in interventions focused on preserving neural tissue health across life.

Next-Generation Bioelectric Medicine: Harnessing the Therapeutic Potential of Neural Implants.

Bioelectric medicine leverages natural signaling pathways in the nervous system to counteract organ dysfunction. This novel approach has potential to address conditions with unmet needs, including heart failure, hypertension, inflammation, arthritis, asthma, Alzheimer's disease, and diabetes. Neural therapies, which target the brain, spinal cord, or peripheral nerves, are already being applied to conditions such as epilepsy, Parkinson's, and chronic pain. While today's therapies have made exciting advancements, their open-loop design-where stimulation is administered without collecting feedback-means that results can be variable and devices do not work for everyone. Stimulation effects are sensitive to changes in neural tissue, nerve excitability, patient position, and more. Closing the loop by providing neural or non-neural biomarkers to the system can guide therapy by providing additional insights into stimulation effects and overall patient condition. Devices currently on the market use recorded biomarkers to close the loop and improve therapy. The future of bioelectric medicine is more holistically personalized. Collected data will be used for increasingly precise application of neural stimulations to achieve therapeutic effects. To achieve this future, advances are needed in device design, implanted and computational technologies, and scientific/medical interpretation of neural activity. Research and commercial devices are enabling the development of multiple levels of responsiveness to neural, physiological, and environmental changes. This includes developing suitable implanted technologies for high bandwidth brain/machine interfaces and addressing the challenge of neural or state biomarker decoding. Consistent progress is being made in these challenges toward the long-term vision of automatically and holistically personalized care for chronic health conditions.

Effects of Simultaneously Performed Dual-Task Training with Aerobic Exercise and Working Memory Training on Cognitive Functions and Neural Systems in the Elderly

Working memory (WM) training (WMT), aerobic exercise training (AET), and dual-task training improve cognitive functions and alter neural systems in older adults. In particular, the effects have been investigated of dual-task training that combines a walking or standing activity (balance exercise) simultaneously performed with cognitive training (which is ecologically difficult for the elderly). In this study, we investigated the effects of simultaneously performed dual-task training incorporating both AET and WMT (SDAEWMT), using a recumbent ergocycle bicycle and a WMT program that provided a portable console and made the training ecologically easy for the elderly. Older adults (65.9±13.7 years old) participated in 3 months of SDAEWMT, WMT, or AET after random allocation, and the effects of SDAEWMT were compared with those of WMT and AET. Prior to and after training, all the subjects underwent cognitive testing, magnetic resonance imaging (MRI) involving diffusion tensor imaging (DTI), and functional MRI during performance of an N-back WM task. SDAEWMT improved executive function (performance of a frontal assessment battery); however, there was no evidence of broader transfer effects or enhanced learning with WMT. SDAEWMT resulted in mean diffusivity changes in brain areas involving the dopaminergic system, suggesting that neural tissue changes occurred in these areas. SDAEWMT also resulted in an increase in brain activity during the 2-back working memory task in brain areas involved in attentional reorientation. These results suggest that SDAEWMT is effective for improving cognitive functions and inducing beneficial neural changes in older adults.

Steinmann Pins and Polymethylmethacrylate Repair of Fourth Lumbar Vertebral Fracture and Dorsocranial Luxation in PuppySteinmann Pins and Polymethylmethacrylate Repair of Fourth Lumbar Vertebral Fracture and Dorsocranial Luxation in Puppy

Background: Acute spinal traumas can lead to irreversible damage associated with vascular and inflammatory changes in neural tissue. Since spine and spinal cord traumas have an unfavorable prognosis in small animals, and reports of the use of Steinmann pins and polymethylmethacrylate repair of lumbar vertebra fracture-luxation in puppies are rare in the literature, the present paper aimed to report the surgical treatment of transversal fracture through the body of the fourth lumbar vertebra, with dorsocranial displacement of the caudal fragment by using Steinmann pins and polymethylmethacrylate in a 7-month-old Labrador Retriever male dog.Case: A 7-month-old intact male Labrador Retriever dog, weighing 24.0 kg was attended at School Veterinary Hospital with a history of hit by car and paraplegia of the hind limbs. On neurological examination was observed no proprioception and no deep pain sensitivity on the both pelvic limbs. The lumbar spinal palpation showed intense pain, and the motor function and patellar reflexes were reduced. The values of haematological and biochemical analysis remained within the reference values for the species. Radiographs revealed a transversal fracture through the body of the fourth lumbar vertebra, with dorsocranial displacement of the caudal fragment, and was decided to perform a surgical treatment by open reduction and internal fixation of the fracture. The dog was positioned in ventral recumbency for surgery, and a dorsal midline incision was made from the second lumbar vertebra to the sixth lumbar vertebra. Two crossed 1.5 mm Kirschner wires were placed through the caudal articular facets of the fourth lumbar vertebra to provide initial stability. Two 2.0 mm Steinmann pins were placed at 60° angle of the bodies of the second and fifth lumbar vertebrae, and third and fourth lumbar vertebrae. This procedure was repeated on the other side of the vertebral bodies. Sixty grams of polymethylmethacrylate bone cement was applied and the fixation was checked for stability. Muscular, subcutaneous tissue and skin was closed routinely. The dog was paraplegic without any pain and used a wheelchair to assist in locomotion, although it still had urinary and faecal incontinence; no tail control; and the implants were not removed.Discussion: Lumbar vertebral injuries, as in the present case frequently, occur secondary to severe trauma (e.g. hit by car) and seem to have a characteristic fracture pattern. The patient became paraplegic due to spinal cord injury and failure of sensitivity and elimination of urine and feces which can be associated with progressive destruction of neuronal tissue due to secondary vascular and inflammatory events. The radiographic exam was used to confirm the spinal injury and determine whether by conservative or surgical treatment. The treatment choice is related to the number of fractured compartments, and the presence or not of compression. Fractures in two or more compartments are indicative of surgical treatment, similar as the present case. Use of Steinmann pins was to make a rigid fixing system compared with block plates used for the same function. Use of polymethylmethacrylate may also become a complication due to the infection, for this reason was prescribed an antibiotic for 15 days. This procedure proved to be effective since the dog showed no signs of infection. According to the characteristics of the present case report, the use of Steinmann pins and polymethylmethacrylate for repair of transversal fracture through the body of the fourth lumbar vertebra, with dorsocranial displacement of the caudal fragment provided an effective and practical means of stabilisation, promoting decompression, and thus, improving the patient's quality of life.

Establishment of cumulative assessment groups of pesticides for their effects on the nervous system.

Cumulative assessment groups of pesticides have been established for five effects on the nervous system: brain and/or erythrocyte acetylcholinesterase inhibition, functional alterations of the motor, sensory and autonomic divisions, and histological neuropathological changes in neural tissue. Sources of uncertainties resulting from the methodological approach and from the limitations in available data and scientific knowledge have been identified and considered. This report supports the publication of a scientific report on cumulative risk assessment to pesticides affecting the nervous system, in which all uncertainties identified for either the exposure assessment or the establishment of the cumulative assessment groups are incorporated into a consolidated risk characterisation.

Effect of long‐term exercise on GDNF expression and innervation in rat skeletal muscle

Sarcopenia is a major cause of frailty and loss of independence in aging individuals. Results of recent studies suggest that changes in neural tissues may contribute to development of sarcopenia. Exercise provides neuroprotection by promoting neurogenesis, decreasing apoptosis, and modulating inflammation, however the mechanisms by which exercise generates these effects are not well understood. Neurotrophic factors are powerful regulators of neuronal maintenance and synaptic strength. Glial cell line‐derived neurotrophic factor (GDNF) is a neurotrophic factor that has been shown to be a potent survival factor for somatic motor neurons that innervate skeletal muscle, but as age continues, GDNF levels in muscle tend to decrease. This study seeks to expand our understanding of the regulatory processes controlling GDNF expression, which will aid in identifying how these processes become disturbed with aging, injury or in neurodegenerative diseases. Our hypothesis is that long‐term exercise will increase GDNF expression, and support neuromuscular junction (NMJ) structures. For these studies Sprague‐Dawley rats (6‐months of age) were exercised, in the form of voluntary running, for 6 months. Controls consisted of an age‐matched sedentary group maintained in cages without access to running wheels. After 6 months of exercise hind‐limb muscles were collected and processed for measurement of GDNF protein content via enzyme‐linked immunosorbent assay. The length and area of motor end plates were quantified via staining with a‐bungarotoxin. Immunohistochemical analysis was performed to detect co‐localization of GDNF and choline acetyltransferase (ChAT), using antibodies against GDNF and ChAT. There was a significant (p ≤ 0.05) increase in length of stained end plates in muscles from exercised rats (36.6 ± 3.5μm) when compared to that in the age‐matched sedentary group (27.6 ± 1.15μm). There was a significant (p ≤ 0.05) increase in area of stained end plates in muscles from exercised rats (616.3 ± 84.9μm2) when compared to that in the age‐matched sedentary group (430.3 ± 30.8μm2). We also observed a trend towards an increase GDNF protein content in muscle from exercised rats compared to tissues from sedentary control rats; however, the effect was not significant. Although, co‐localization between GDNF and ChAT appeared more apparent in tissues from exercised rats. These findings suggest that increased physical activity enhances structural neuroplasticity in NMJ elements and may possibly lead to enhanced neuromuscular function. Understanding the activity dependent regulation of neurotrophic factor expression and neural plasticity in the neuromuscular system may help in identifying novel targets for pharmacological development.Support or Funding InformationThis work was supported by a grant from the Faculty Research and Creative Activities Award, Western Michigan University, NIH grant 1 R15 AG022908‐01A2, NSF grant DBI 0552517.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A mechanoelectrical coupling model of neurons under stretching

Neurons are situated in a microenvironment composed of various mechanical cues, where stretching is thought to have a major impact on neurons, resulting in microstructural changes in neural tissue and further leading to abnormal electrophysiological function. In spite of significant experimental efforts, the underlying mechanism remains elusive, more works are needed to provide a detailed description of the process that leads to the observed phenomena. Here, we developed a mechanoelectrical coupling model of central neurons under stretching and specially considered the plastic deformation of neurons. With the model, we showed that the increasing axial strain induces a decreased membrane action potential and a more frequent neuronal firing, which agree well with experimental observations reported in the literature. The simulation results also showed a faster electrophysiological signal conduction. Our model provides a reference for the prediction and regulation of neuronal function under simplified conditions of mechanical loadings.

Detection of neural light-scattering activity in vivo: optical transmittance studies in the rat brain

Optical studies of ex vivo brain slices where blood is absent show that neural activity is accompanied by significant intrinsic optical signals (IOS) related to activity-dependent scattering changes in neural tissue. However, the neural scattering signals have been largely ignored in vivo in widely-used IOS methods where absorption contrast from hemoglobin was employed. Changes in scattering were observed on a time scale of seconds in previous brain slice IOS studies, similar to the time scale for the hemodynamic response. Therefore, potential crosstalk between the scattering and absorption changes may not be ignored if they have comparable contributions to IOS. In vivo, the IOS changes linked to neural scattering have been elusive. To isolate neural scattering signals in vivo, we employed 2 implantable optodes for small-separation (2 mm) transmission measurements of local brain tissue in anesthetized rats. This unique geometry enables us to separate neuronal activity-related changes in neural tissue scattering from changes in blood absorption based upon the direction of the signal change. The changes in IOS scattering and absorption in response to up-states of spontaneous neuronal activity in cortical or subcortical structures have strong correlation to local field potentials, but significantly different response latencies. We conclude that activity-dependent neural tissue scattering in vivo may be an additional source of contrast for functional brain studies that provides complementary information to other optical or MR-based systems that are sensitive to hemodynamic contrast.

The effect of nerve mobilization exercise in patients with rheumatoid arthritis: a pilot study.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the joints. The neurogenic inflammatory mechanism plays an important role in the inflammatory process of RA, and pathological changes in neural tissues in RA have also been noted. We aim to investigate treatment of the nervous system to relieve joint pain and inflammation in RA. Nerve mobilization, a nervous system-specific therapeutic exercise, was applied on RA patients to determine the effect of nerve mobilization on joint inflammation. Twelve RA patients were recruited from the community and were randomised into an experimental and a control group. In the experimental group, the subjects were taught a set of nerve mobilization exercises while the subjects in the control group were taught a set of gentle joint mobilization exercises. Both groups were instructed to practice the exercises daily. After a 4-week period, their RA pain scale (RAPS) and pain scores were examined, as well as the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Subjects in the experimental group showed improvements in RAPS and pain scores after 4 weeks of nerve mobilization exercises, while CRP and ESR values remained unaffected. These preliminary data showed that nerve mobilization exercises might be beneficial in controlling joint pain in RA patients.

Performances of diffusion kurtosis imaging and diffusion tensor imaging in detecting white matter abnormality in schizophrenia.

Diffusion kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI), exhibiting improved sensitivity and specificity in detecting developmental and pathological changes in neural tissues. However, little attention was paid to the performances of DKI and DTI in detecting white matter abnormality in schizophrenia. In this study, DKI and DTI were performed in 94 schizophrenia patients and 91 sex- and age-matched healthy controls. White matter integrity was assessed by fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK) of DKI and FA, MD, AD and RD of DTI. Group differences in these parameters were compared using tract-based spatial statistics (TBSS) (P < 0.01, corrected). The sensitivities in detecting white matter abnormality in schizophrenia were MK (34%) > AK (20%) > RK (3%) and RD (37%) > FA (24%) > MD (21%) for DKI, and RD (43%) > FA (30%) > MD (21%) for DTI. DKI-derived diffusion parameters (RD, FA and MD) were sensitive to detect abnormality in white matter regions (the corpus callosum and anterior limb of internal capsule) with coherent fiber arrangement; however, the kurtosis parameters (MK and AK) were sensitive to reveal abnormality in white matter regions (the juxtacortical white matter and corona radiata) with complex fiber arrangement. In schizophrenia, the decreased AK suggests axonal damage; however, the increased RD indicates myelin impairment. These findings suggest that diffusion and kurtosis parameters could provide complementary information and they should be jointly used to reveal pathological changes in schizophrenia.

Assessment of motor recovery and MRI correlates in a porcine spinal cord injury model

The study concentrated on behavioral and magnetic resonance imaging (MRI) characteristics in a porcine spinal cord injury model. Six adult minipigs weighing 32–35 kg were narcotized by thiopental, intubated, and placed on a volume-cycled ventilator. Anaesthesia was maintained by 1.5% sevoflurane with oxygen. Following location of the 1st lumbar vertebra animals were fastened in an immobilization frame. The spinal cord, exposed through a laminectomy, was compressed by a 5 mm thick circular rod with a peak force of 0.8 kg at a velocity of 3 cm·s-1. The next day the minipigs were paraplegic but improved rapidly to paraparesis. On the 12th postoperative day they were euthanasied. Neural tissue changes were evaluated by post mortem MRI, which showed damage to the spinal cord white and/or gray matter in the epicentre of compression with longitudinal spreading over one segment cranially and caudally. Statistical analyses performed by Spearman’s rho test revealed positive correlations between damaged areas and the whole area of the spinal cord white/gray matter (P = 0.047; rs = 0.742) and (P = 0.002; rs = 0.943), respectively. The study confirmed the reliability and reproducibility of the utilised model of spinal cord trauma. The structural changes in the epicentre of injury did not impede the rapid but incomplete recovery of motor functions.

Modelling the interaction of structural and synaptic plasticity

Recent experiments show that learning is associated with structural changes in neural tissue [1,2]. The underlying mechanism, named structural plasticity, drives the formation of new synapses and the removal of existing ones on a timescale of days to weeks. This enlarges the potential for information storage in neuronal networks [3] and is, thus, important for understanding long-term memory formation. On shorter timescales (minutes to hours) another process - synaptic plasticity - influences the transmission efficiency (weights) of a synapse and, therefore, also contributes to information storage. We investigate the interaction between these two processes - still widely unknown - in the following rather simple model: We use rate based neurons with the total transmission efficiency between two neurons being just the sum of weights of all synapses connecting these two neurons. Thus, the number of synapses as well as their weights influence the same quantity and we can investigate the effects arising from structural and synaptic plasticity competing on different timescales. Synaptic plasticity is modeled by Hebbian learning with weight-dependent synaptic scaling [4]. For structural plasticity we have to assume a certain number of potential synaptic sites. The formation of a synapse at each of these potential synaptic sites happens at random with a fixed formation probability. The removal of existing synapses also happens randomly, but with a probability, which depends on weight and postsynaptic activity. Although the interaction of these processes is quite complex, we show that the system converges to a stable state. In this state the activity determines the probability distribution of number and strength of synapses between neurons. This interplay could also serve to form highly interconnected clusters, which are candidates for memory representation (cell assemblies).

Effect of cerebrovascular changes on brain DTI quantitation: a hypercapnia study

Quantitative diffusion tensor imaging (DTI) offers a valuable tool to probe the microstructural changes in neural tissues in vivo, where absolute quantitation accuracy and reproducibility are essential. It has been long recognized that measurement of apparent diffusion coefficient (ADC) using DTI could be influenced by the presence of water molecules in cerebrovasculature. However, little is known about to what extent such blood signal affects DTI quantitation. In this study, we quantitatively examined the effect of cerebral hemodynamic change on DTI indices by using a standard multislice echo planar imaging (EPI) spin echo (SE) DTI acquisition protocol and a rat model of hypercapnia. In response to 5% CO2 challenge, mean, radial and axial diffusivities measured with diffusion factor (b-value) of b=1.0 ms/μm2 were found to increase in whole brain (1.52%±0.22%, 1.66%±0.16% and 1.35%±0.37%, respectively), gray matter (1.56%±0.23%, 1.63%±0.14% and 1.47%±0.45%, respectively) and white matter regions (1.45%±0.28%, 1.88%±0.33% and 1.10%±0.26%, respectively). Fractional anisotropy (FA) was found to decrease by 1.67%±0.38%, 1.91%±0.59% and 1.46%±0.30% in whole brain, gray matter and white matter regions, respectively. In addition, these diffusivity increases and FA decreases became more pronounced at a lower b-value (b=0.3 ms/μm2). The results indicated that in vivo DTI quantitation in brain can be contaminated by vascular factors on the order of few percentages. Consequently, alterations in cerebrovasculature and hemodynamics can affect the DTI quantitation and its efficacy in characterizing the neural tissue microstructures in normal and diseased states. Caution should be taken in designing and interpreting quantitative DTI studies as all DTI indices can be potentially confounded by physiologic conditions and by cerebrovascular and hemodynamic characteristics.

Histomorphometric changes in repaired mouse sciatic nerves are unaffected by the application of a scar-reducing agent.

Microsurgical repair of transected peripheral nerves is compromised by the formation of scar tissue and the development of a neuroma, thereby limiting the success of regeneration. The aim of this study was to quantify histomorphometrically the structural changes in neural tissue that result from repair, and determine the effect of mannose-6-phosphate (M6P), a scar-reducing agent previously shown to enhance regeneration. In anaesthetised C57-black-6 mice, the left sciatic nerve was sectioned and repaired using four epineurial sutures. Either 100 μL of 600 mm M6P (five animals) or 100 μL of phosphate-buffered saline (placebo controls, five animals) was injected into and around the nerve repair site. A further group acted as sham-operated controls. After recovery for 6 weeks, the nerve was harvested for analysis using light and electron microscopy. Analysis revealed that when compared with sham controls, myelinated axons had smaller diameters both proximal and distal to the repair. Myelinated axon counts, axonal density and size all decreased across the repair site. There were normal numbers and densities of non-myelinated axons both proximal and distal to the repair. However, there were more Remak bundles distal to the repair site, and fewer non-myelinated axons per Remak bundle. Application of M6P did not affect any of these parameters.