A Distinct Population of L6 Neurons in Mouse V1 Mediate Cross-Callosal Communication.

Through the corpus callosum, interhemispheric communication is mediated by callosal projection (CP) neurons. Using retrograde labeling, we identified a population of layer 6 (L6) excitatory neurons as the main conveyer of transcallosal information in the monocular zone of the mouse primary visual cortex (V1). Distinct from L6 corticothalamic (CT) population, V1 L6 CP neurons contribute to an extensive reciprocal network across multiple sensory cortices over two hemispheres. Receiving both local and long-range cortical inputs, they encode orientation, direction, and receptive field information, while are also highly spontaneous active. The spontaneous activity of L6 CP neurons exhibits complex relationships with brain states and stimulus presentation, distinct from the spontaneous activity patterns of the CT population. The anatomical and functional properties of these L6 CP neurons enable them to broadcast visual and nonvisual information across two hemispheres, and thus may play a role in regulating and coordinating brain-wide activity events.

Ocular dominance columns in V1 are more susceptible than associated callosal patches to imbalance of eye input during precritical and critical periods.

In Long Evans rats, ocular dominance columns (ODCs) in V1 overlap with patches of callosal connections. Using anatomical tracers, we found that ODCs and callosal patches are present at postnatal day 10 (P10), several days before eye opening, and about 10 days before the activation of the critical period for ocular dominance plasticity (~P20). In rats monocularly enucleated at P10 and perfused ~P20, ODCs ipsilateral to the remaining eye desegregated, indicating that rat ODCs are highly susceptible to monocular enucleation during a precritical period. Monocular enucleation during the critical period exerted significant, although smaller, effects. Monocular eye lid suture during the critical period led to a significant expansion of the ipsilateral projection from the nondeprived eye, whereas the contralateral projection invaded into, and intermixed with, ipsilateral ODCs innervated by the deprived eye. We propose that this intermixing allows callosal connections to contribute to the effects of monocular deprivation assessed in the hemisphere ipsilateral to the nondeprived eye. The ipsilateral and contralateral projections from the deprived eye did not undergo significant shrinkage. In contrast, we found that callosal patches are less susceptible to imbalance of eye input. In rats monocularly enucleated during either the precritical or critical periods, callosal patches were maintained in the hemisphere ipsilateral to the remaining eye, but desegregated in the hemisphere ipsilateral to the enucleated orbit. Callosal patches were maintained in rats binocularly enucleated at P10 or later. Similarly, monocular deprivation during the critical period had no significant effect on callosal patches in either hemisphere.

Quantitative susceptibility mapping of the rat brain after traumatic brain injury.

The primary lesion arising from the initial insult after traumatic brain injury (TBI) triggers a cascade of secondary tissue damage, which may also progress to connected brain areas in the chronic phase. The aim of this study was, therefore, to investigate variations in the susceptibility distribution related to these secondary tissue changes in a rat model after severe lateral fluid percussion injury. We compared quantitative susceptibility mapping (QSM) and R2 * measurements with histological analyses in white and grey matter areas outside the primary lesion but connected to the lesion site. We demonstrate that susceptibility variations in white and grey matter areas could be attributed to reduction in myelin, accumulation of iron and calcium, and gliosis. QSM showed quantitative changes attributed to secondary damage in areas located rostral to the lesion site that appeared normal in R2 * maps. However, combination of QSM and R2 * was informative in disentangling the underlying tissue changes such as iron accumulation, demyelination, or calcifications. Therefore, combining QSM with R2 * measurement can provide a more detailed assessment of tissue changes and may pave the way for improved diagnosis of TBI, and several other complex neurodegenerative diseases.

Myelin and Lipid Composition of the Corpus Callosum in Mucopolysaccharidosis Type I Mice.

Mucopolysaccharidosis type I (MPS I) is a lysosomal disease with progressive central nervous system involvement. This study examined the lipid, cholesterol, and myelin basic protein composition of white matter in the corpus callosum of MPS I mice. We studied 50 week-old, male MPS I mice and littermate, heterozygote controls (n = 12 per group). Male MPS I mice showed lower phosphatidylcholine and ether-linked phosphatidylcholine quantities than controls (p < 0.05). Twenty-two phospholipid or ceramide species showed significant differences in percent of total. Regarding specific lipid species, MPS I mice exhibited lower quantities of sphingomyelin 18:1, phosphatidylserine 38:3, and hexosylceramide d18:1(22:1) mH2 O than controls. Principal components analyses of polar, ceramide, and hexosylceramide lipids, respectively, showed some separation of MPS I and control mice. We found no significant differences in myelin gene expression, myelin basic protein, or total cholesterol in the MPS I mice versus heterozygous controls. There was a trend toward lower proteolipid protein-1 levels in MPS I mice (p = 0.06). MPS I mice show subtle changes in white matter composition, with an unknown impact on pathogenesis in this model.

Influence of ocular dominance columns and patchy callosal connections on binocularity in lateral striate cortex: Long Evans versus albino rats.

In albino rats, it has been reported that lateral striate cortex (V1) is highly binocular, and that input from the ipsilateral eye to this region comes through the callosum. In contrast, in Long Evans rats, this region is nearly exclusively dominated by the contralateral eye even though it is richly innervated by the callosum (Laing, Turecek, Takahata, & Olavarria, 2015). We hypothesized that the inability of callosal connections to relay ipsilateral eye input to lateral V1 in Long Evans rats is a consequence of the existence of ocular dominance columns (ODCs), and of callosal patches in register with ipsilateral ODCs in the binocular region of V1 (Laing et al., 2015). We therefore predicted that in albino rats input from both eyes intermix in the binocular region, without segregating into ODCs, and that callosal connections are not patchy. Confirming our predictions, we found that inputs from both eyes, studied with the transneuronal tracer WGA-HRP, are intermixed in the binocular zone of albinos, without segregating into ODCs. Similarly, we found that callosal connections in albino rats are not patchy but instead are distributed homogeneously throughout the callosal region in V1. We propose that these changes allow the transcallosal passage of ipsilateral eye input to lateral striate cortex, increasing its binocularity. Thus, the binocular region in V1 of albino rats includes lateral striate cortex, being therefore about 25% larger in area than the binocular region in Long Evans rats. Our findings provide insight on the role of callosal connections in generating binocular cells.

MRI Evidence of Altered Callosal Sodium in Mild Traumatic Brain Injury.

BACKGROUND AND PURPOSE: Mild traumatic brain injury is a leading cause of death and disability worldwide with 42 million cases reported annually, increasing the need to understand the underlying pathophysiology because this could help guide the development of targeted therapy. White matter, particularly the corpus callosum, is susceptible to injury. Animal models suggest stretch-induced mechanoporation of the axonal membrane resulting in ionic shifts and altered sodium ion distribution. The purpose of this study was to compare the distribution of total sodium concentration in the corpus callosum between patients with mild traumatic brain injury and controls using sodium (23Na) MR imaging. MATERIALS AND METHODS: Eleven patients with a history of mild traumatic brain injury and 10 age- and sex-matched controls underwent sodium (23Na) MR imaging using a 3T scanner. Total sodium concentration was measured in the genu, body, and splenium of the corpus callosum with 5-mm ROIs; total sodium concentration of the genu-to-splenium ratio was calculated and compared between patients and controls. RESULTS: Higher total sodium concentration in the genu (49.28 versus 43.29 mmol/L, P = .01) and lower total sodium concentration in the splenium (which was not statistically significant; 38.35 versus 44.06 mmol/L, P = .08) was seen in patients with mild traumatic brain injury compared with controls. The ratio of genu total sodium concentration to splenium total sodium concentration was also higher in patients with mild traumatic brain injury (1.3 versus 1.01, P = .001). CONCLUSIONS: Complex differences are seen in callosal total sodium concentration in symptomatic patients with mild traumatic brain injury, supporting the notion of ionic dysfunction in the pathogenesis of mild traumatic brain injury. The total sodium concentration appears to be altered beyond the immediate postinjury phase, and further work is needed to understand the relationship to persistent symptoms and outcome.

Biospectroscopic Imaging Provides Evidence of Hippocampal Zn Deficiency and Decreased Lipid Unsaturation in an Accelerated Aging Mouse Model.

Western society is facing a health epidemic due to the increasing incidence of dementia in aging populations, and there are still few effective diagnostic methods, minimal treatment options, and no cure. Aging is the greatest risk factor for memory loss that occurs during the natural aging process, as well as being the greatest risk factor for neurodegenerative disease such as Alzheimer's disease. Greater understanding of the biochemical pathways that drive a healthy aging brain toward dementia (pathological aging or Alzheimer's disease), is required to accelerate the development of improved diagnostics and therapies. Unfortunately, many animal models of dementia model chronic amyloid precursor protein overexpression, which although highly relevant to mechanisms of amyloidosis and familial Alzheimer's disease, does not model well dementia during the natural aging process. A promising animal model reported to model mechanisms of accelerated natural aging and memory impairments, is the senescence accelerated murine prone strain 8 (SAMP8), which has been adopted by many research group to study the biochemical transitions that occur during brain aging. A limitation to traditional methods of biochemical characterization is that many important biochemical and elemental markers (lipid saturation, lactate, transition metals) cannot be imaged at meso- or microspatial resolution. Therefore, in this investigation, we report the first multimodal biospectroscopic characterization of the SAMP8 model, and have identified important biochemical and elemental alterations, and colocalizations, between 4 month old SAMP8 mice and the relevant control (SAMR1) mice. Specifically, we demonstrate direct evidence of Zn deficiency within specific subregions of the hippocampal CA3 sector, which colocalize with decreased lipid unsaturation. Our findings also revealed colocalization of decreased lipid unsaturation and increased lactate in the corpus callosum white matter, adjacent to the hippocampus. Such findings may have important implication for future research aimed at elucidating specific biochemical pathways for therapeutic intervention.

Myelin structure in unfixed, single nerve fibers: Scanning X-ray microdiffraction with a beam size of 200nm.

Previous raster-scanning with a 1µm X-ray beam of individual, myelinated fibers from glutaraldehyde-fixed rat sciatic nerve revealed a spatially-dependent variation in the diffraction patterns from single fibers. Analysis indicated differences in the myelin periodicity, membrane separations, distribution of proteins, and orientation of membrane lamellae. As chemical fixation is known to produce structural artifacts, we sought to determine in the current study whether the structural heterogeneity is intrinsic to unfixed myelin. Using a 200nm-beam that was about five-fold smaller than before, we raster-scanned individual myelinated fibers from both the peripheral (PNS; mouse and rat sciatic nerves) and central (CNS; rat corpus callosum) nervous systems. As expected, the membrane stacking in the internodal region was nearly parallel to the fiber axis and in the paranodal region it was perpendicular to the axis. A myelin lattice was also frequently observed when the incident beam was injected en face to the sheath. Myelin periodicity and diffracted intensity varied with axial position along the fiber, as did the calculated membrane profiles. Raster-scanning with an X-ray beam at sub-micron resolution revealed for the first time that the individual myelin sheaths in unfixed nerve are heterogeneous in both membrane structure and packing.

Peptidomic analysis of the anterior temporal lobe and corpus callosum from schizophrenia patients.

Schizophrenia is a complex disorder hypothesized to develop from a combination of genetic, neurodevelopmental, and environmental factors. Molecules that are directly involved in the pathogenesis of schizophrenia and may serve as biomarker candidates can be identified with "omics" approaches such as proteomics and peptidomics. In this context, we performed a peptidomic study in schizophrenia postmortem brains, to our knowledge the first such study in schizophrenia patients. We investigated the anterior temporal lobe (ATL) and corpus callosum (CC) by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and a label-free ion quantification technique based on data-dependent acquisition (DDA). Results indicated alterations in a specific intracellular neurogranin peptide in both the ATL and CC and a decrease of PepH, a fragment of histone H2B type 1-H intracellular peptide, in the ATL. PepH was tested in serum-deprived Neuro2A cells and showed a protective effect against cell death. Cells were also challenged with lipopolysaccharide (LPS), and PepH was able to prevent the endotoxic effects of LPS. Our data suggest that specific intracellular peptides are altered in schizophrenia patients. The potential biological activity of PepH supports intracellular peptides as novel targets in the study not only of schizophrenia but also of other neuropsychiatric diseases. BIOLOGICAL SIGNIFICANCE: Psychiatric disorders are considerably more difficult to diagnose in their early stages. Usually, by the time the diagnosis is clear and clinical treatment can be started, the disorder is already established and thus of greater severity. Consequently, the scientific community has been searching for biomarker candidates that can aid the early detection of such disorders and for novel therapeutics to improve treatment or at least delay disease progression. Moreover, key molecules involved in the establishment of psychiatric diseases may help the understanding of their pathogenesis and thus drive the development of more effective treatments. The present work screened peptides that might be possible novel targets to control cell machinery in schizophrenia and identified an intracellular peptide with potential cytoprotective activity. To our knowledge, this is the first peptidomic study in schizophrenia patients.

Field inhomogeneity correction for gradient echo myelin water fraction imaging.

PURPOSE: Recently, the multi-echo gradient echo (MGRE) sequence has been proposed for multicomponent T2* (MC T2*) based myelin water fraction (MWF) mapping. This approach has appeal because it can provide fast whole-brain coverage, has low specific absorption rate, and short echo spacing. However, the MGRE signal requires correction for accurate MWF mapping, because of its sensitivity to magnetic field inhomogeneities (ΔB0 ). We propose a ΔB0 correction method for 2D MGRE data obtained for MWF mapping. THEORY AND METHODS: Latter-echo MGRE data were fit to estimate B0 gradients in the slice-select direction ( Gz). The decay signal was corrected for the effects of Gz, and MC T2* analysis was performed using nonnegative least-squares fitting. The method was evaluated using simulations and its performance demonstrated in healthy volunteers. RESULTS: Simulations showed that MWFs are significantly biased in the presence of Gz and that our correction method leads to accurate MWF estimates. In vivo MWF maps obtained from corrected data showed recovery of MWF estimates in areas of high ΔB0, and overall good agreement with literature values obtained with the reference MC T2-based method. CONCLUSION: A new algorithm was presented for ΔB0 correction of 2D MGRE echo data acquired for MWF imaging. Simulations and in vivo data showed an improvement in MWF estimates. Magn Reson Med 78:49-57, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Chemical Analysis in the Corpus Callosum Following Traumatic Axonal Injury using Fourier Transform Infrared Microspectroscopy: A Pilot Study.

Evaluating traumatic axonal injury remains challenging in clinical and forensic sciences as its identification is difficult using routine diagnostic methods. This study used Fourier transform infrared microspectroscopy to detect TAI within the corpus callosum in an animal model. Protein conformational analysis revealed significantly increased ß-sheet and ß-turn contents paralleled by a decrease in α-helix content at 24 h postinjury, while the antiparallel ß-sheet content was decreased at 12 h postinjury. Compared with the control group, the lipid/protein ratio was significantly reduced in all of the injured groups. At 24 h postinjury, there were increases in the olefinic=CH and CH3 group of lipids accompanied by the decreased CH2 group, but the results at 12 and 72 h were contrary to that at 24 h. Our study showed that FTIRM could differentiate injured from normal white matter at different time points following TBI via examination of these infrared spectral parameters.

Reproducibility and optimization of in vivo human diffusion-weighted MRS of the corpus callosum at 3 T and 7 T.

Diffusion-weighted MRS (DWS) of brain metabolites enables the study of cell-specific alterations in tissue microstructure by probing the diffusion of intracellular metabolites. In particular, the diffusion properties of neuronal N-acetylaspartate (NAA), typically co-measured with N-acetylaspartyl glutamate (NAAG) (NAA + NAAG = tNAA), have been shown to be sensitive to intraneuronal/axonal damage in pathologies such as stroke and multiple sclerosis. Lacking, so far, are empirical assessments of the reproducibility of DWS measures across time and subjects, as well as a systematic investigation of the optimal acquisition parameters for DWS experiments, both of which are sorely needed for clinical applications of the method. In this study, we acquired comprehensive single-volume DWS datasets of the human corpus callosum at 3 T and 7 T. We investigated the inter- and intra-subject variability of empirical and modeled diffusion properties of tNAA [D(avg) (tNAA) and D(model) (tNAA), respectively]. Subsequently, we used a jackknife-like resampling approach to explore the variance of these properties in partial data subsets reflecting different total scan durations. The coefficients of variation (C(V)) and repeatability coefficients (C(R)) for D(avg) (tNAA) and D(model) (tNAA) were calculated for both 3 T and 7 T, with overall lower variability in the 7 T results. Although this work is limited to the estimation of the diffusion properties in the corpus callosum, we show that a careful choice of diffusion-weighting conditions at both field strengths allows the accurate measurement of tNAA diffusion properties in clinically relevant experimental time. Based on the resampling results, we suggest optimized acquisition schemes of 13-min duration at 3T and 10-min duration at 7 T, whilst retaining low variability (C(V) ≈ 8%) for the tNAA diffusion measures. Power calculations for the estimation of D(model )(tNAA) and D(avg) (tNAA) based on the suggested schemes show that less than 21 subjects per group are sufficient for the detection of a 10% effect between two groups in case-control studies.

Clinical MRI for iron detection in Parkinson's disease.

We studied nonheme iron in Parkinson's disease (PD) using clinically available MRI in 36 patients and 21 healthy volunteers. The subjects underwent thorough clinical investigation, including 3-T MRI. Quantitative R2* was able to reflect symptoms of PD. In addition, the clinically used susceptibility-weighted imaging differentiated between controls and patients, whereas T2-weighted imaging did not. Disease-related changes were present not only in substantia nigra but also in globus pallidus. Such changes are associated with neurodegeneration, reflecting the severity of motor impairment.

Metallic gold slows disease progression, reduces cell death and induces astrogliosis while simultaneously increasing stem cell responses in an EAE rat model of multiple sclerosis.

Multiple sclerosis (MS) is the most common neurodegenerative disease in the Western world affecting younger, otherwise healthy individuals. Today no curative treatment exists. Patients suffer from recurring attacks caused by demyelination and underlying neuroinflammation, ultimately leading to loss of neurons. Recent research shows that bio-liberation of gold ions from metallic gold implants can ameliorate inflammation, reduce apoptosis and promote proliferation of neuronal stem cells (NSCs) in a mouse model of focal brain injury. Based on these findings, the present study investigates whether metallic gold implants affect the clinical signs of disease progression and the pathological findings in experimental autoimmune encephalomyelitis (EAE), a rodent model of MS. Gold particles 20-45 µm suspended in hyaluronic acid were bilaterally injected into the lateral ventricles (LV) of young Lewis rats prior to EAE induction. Comparing gold-treated animals to untreated and vehicle-treated ones, a statistically significant slowing of disease progression in terms of reduced weight loss was seen. Despite massive inflammatory infiltration, terminal deoxynucleotidyl transferase dUTP nick end labeling staining revealed reduced apoptotic cell death in disease foci in the brain stem of gold-treated animals, alongside an up-regulation of glial fibrillary acidic protein-positive reactive astrocytes near the LV and in the brain stem. Cell counting of frizzled-9 and nestin-stained cells showed statistically significant up-regulation of NSCs migrating from the subventricular zone. Additionally, the neuroprotective proteins Metallothionein-1 and -2 were up-regulated in the corpus callosum. In conclusion, this study is the first to show that the presence of small gold implants affect disease progression in a rat model of MS, increasing the neurogenic response and reducing the loss of cells in disease foci. Gold implants might thus improve clinical outcome for MS patients and further research into the long-term effects of such localized gold treatment is warranted.

Involvement of dopaminergic and serotonergic systems in the neurobehavioral toxicity of lambda-cyhalothrin in developing rats.

In view of extensive uses of lambda-cyhalothrin, a new generation type II synthetic pyrethroid, human exposure is quite imminent. The present study has therefore been carried out to investigate effect of lambda-cyhalothrin on brain dopaminergic and serotonergic systems and functional alterations associated with them. Post-lactational exposure to lambda-cyhalothrin (1.0 mg/kg or 3.0 mg/kg body weight, p.o.) from PD22 to PD49 caused a significant decrease in the motor activity and rota-rod performance in rats on PD50 as compared to controls. Decrease in motor activity in lambda-cyhalothrin treated rats was found to persist 15 days after withdrawal of exposure on PD65 while a trend of recovery in rota-rod performance was observed. A decrease in the binding of ³H-Spiperone, known to label dopamine-D2 receptors in corpus striatum associated with decreased expression of tyrosine hydroxylase (TH)-immunoreactivity and TH protein was observed in lambda-cyhalothrin treated rats on PD50 and PD65 compared to controls. Increase in the binding of ³H-Ketanserin, known to label serotonin-2A receptors in frontal cortex was observed in lambda-cyhalothrin exposed rats on PD50 and PD65 as compared to respective controls. The changes were more marked in rats exposed to lambda-cyhalothrin at a higher dose (3.0 mg/kg) and persisted even 15 days after withdrawal of exposure. The results exhibit vulnerability of developing rats to lambda-cyhalothrin and suggest that striatal dopaminergic system is a target of lambda-cyhalothrin. Involvement of serotonin-2A receptors in the neurotoxicity of lambda-cyhalothrin is also suggested. The results further indicate that neurobehavioral changes may be more intense in case exposure to lambda-cyhalothrin continues.

A steroid isolated from the water mold Achlya heterosexualis induces neurogenesis in vitro and in vivo.

Using 22R-hydroxycholesterol as a sub-structure to screen natural compound databases, we identified a naturally occurring steroid (sc-7) with a 16-acetoxy-22R-hydroxycholesterol moiety, in which the hydroxyl groups in positions 3 and 22 are esterified by an acetoxy group and in which the carbon in position 26 carries a functional diacetylamino. sc-7 is an analog of the sex steroids dehydro-oogoniol and antheridiol, can be isolated from the water mold Achlya heterosexualis, and promoted neurogenesis in vitro and in vivo. Mouse embryonic teratocarcinoma P19 cells exposed to sc-7 for 2days followed by a 5-day wash-out differentiated into cholinergic neurons that expressed specific neuronal markers and displayed axonal formation. Axons continued growing up to 28days after treatment. In vivo, infusion of sc-7 for 2weeks into the left ventricle of the rat brain followed by a 3-week wash-out induced bromodeoxyuridine uptake by cells of the ependymal layer and subventricular zone that co-localized with doublecortin and glial fibrillary acidic protein immunostaining, demonstrating induction of proliferation and differentiation of neuronal progenitors. Migrating neuroblasts were also observed in the corpus callosum. Thus, under these experimental conditions, adult ependymal cells resumed proliferation and differentiation. Taken together, these results suggest that sc-7 is an interesting molecule for stimulating in situ neurogenesis from resident neuronal progenitors as part of neuron replacement therapy. sc-7 did not bind to nuclear steroid receptors and was not metabolized as a steroid, supporting our hypothesis that the neurogenic effect of sc-7 is not likely due to a steroid-like effect.

Segmented 2D-selective RF excitations with weighted averaging and flip angle adaptation for MR spectroscopy of irregularly shaped voxel.

A weighted averaging scheme with flip angle adaptation is presented for segmented 2D-selective RF excitations and applied to single-line segments of a blipped-planar trajectory. Segments covering the central k-space, i.e. those with significant signal contributions, are averaged more often than the (outer) segments with low RF amplitudes and minor signal contributions. For compensation, these outer segments are applied with an increased RF amplitude, i.e. a larger flip angle, such that an unaltered signal contribution is obtained in a reduced number of shots. Numerical simulations and experiments in phantoms and the human brain in vivo demonstrate that the approach considerably increases the signal efficiency, i.e. the signal accumulated per time unit, without introducing profile distortions. Its application to single-voxel MR spectroscopy of a corpus-callosum-shaped region-of-interest yielded, due to an optimum coverage of the target volume, higher signal amplitudes than conventional localization based on cross-sectional RF excitations. Thus, the approach could improve the reliability of single-voxel MR spectroscopy.

Fiber composition in the planum temporale sector of the corpus callosum in chimpanzee and human.

In humans the planum temporale is usually larger in the left hemisphere and related to Wernicke's language complex. A slighter leftward asymmetry, unrelated to vocal perception, was reported in the chimpanzee. Searching for differences between the human brain and that of the chimpanzee, we analyzed the fiber composition in the sector of the corpus callosum containing fibers from the planum temporale. This sector was identified in chimpanzee and human myelin-stained materials by comparison with anatomical tract-tracing in the macaque monkey. The axon diameters in the planum temporale sector of the corpus callosum were not different in human and chimpanzee, suggesting that this feature of the output of the planum temporale was preserved since the common ancestor of both species and may not be uniquely related to language. However, the larger size of the human brain probably amplified slow and temporally dispersed conduction between the hemispheres. A trend with thicker axons dorsally and thinner axons ventrally in the corpus callosum was evident in human brain, but was much weaker, or absent in the chimpanzee.

Sex differences in the human corpus callosum microstructure: a combined T2 myelin-water and diffusion tensor magnetic resonance imaging study.

Sex differences in structure and organization of the corpus callosum (CC) have been identified in healthy adults and may be linked to distinct functional lateralization and processing in men and women. Magnetic resonance imaging (MRI) has facilitated noninvasive assessment of CC sex differences in morphology by volumetric imaging and microstructural organization by diffusion tensor imaging (DTI). Incorporation of recently developed myelin-water fraction (MWF) imaging may improve our understanding of CC sex differences. The aim of the current study was to combine DTI and diffusion tractography with MWF imaging to investigate CC sex differences in 22 healthy adults (11 male, 11 female). We performed MWF imaging using a 5-echo linear combination of spin echo images, and quantified mean diffusivity, axial diffusivity, radial diffusivity and fractional anisotropy (FA) by DTI. Fiber density index (FDi) was quantified using diffusion tractography. The MWF in males was significantly greater than females for the rostral body (p<0.05) and posterior midbody (p<0.005); whereas, the splenium MWF in males was significantly less than females (p<0.05). The DTI analysis revealed significantly increased FA in males compared with females within the genu of the CC (p<0.05). No significant sex-differences existed for mean diffusivity, axial diffusivity, radial diffusivity or FDi. Correlations between DTI parameters and MWF were significant but weak. Results of this study demonstrate regionally dependent sex differences in microstructural composition and organization of the CC and the lack of correlation between DTI and MWF suggest both measures provide unique information within the CC.

Delayed P2X4R expression after hypoxia-ischemia is associated with microglia in the immature rat brain.

In a preterm hypoxia-ischemia model in the post-natal day 3 rat, we characterized how the expression of purine ionotropic P2X(4) receptors change in the brain post-insult. After hypoxia-ischemia, P2X(4) receptor expression increased significantly and was associated with a late increase in ionised calcium binding adapter molecule-1 protein expression indicative of microglia cell activation. Minocycline, a potent inhibitor of microglia, attenuated the hypoxia-ischemia-induced increase in P2X(4) receptor expression. We postulate that P2X(4) receptor-positive microglia may represent a population of secondary injury-induced activated microglia. Future studies will determine whether this population contributes to the progression of injury in the immature brain.