Magnetic resonance elastography of the ageing brain in normal and demented populations: A systematic review

The aim of this systematic review was to evaluate the ability of magnetic resonance elastography (MRE) to identify significant changes in brain mechanical properties during normal and pathological aging. PubMed, Web of Science and Scopus were searched for human studies using MRE to assess brain mechanical properties in cognitively healthy individuals, individuals at risk of dementia or patients diagnosed with dementia. Study characteristics, sample demographics, clinical characterization and main MRE outcomes were summarized in a table. A total of 19 studies (nine aging, 10 dementia), comprising 700 participants, were included. The main findings were decreased cerebral stiffness along aging, with rates of annual change ranging from −0.008 to −0.025 kPa per year. Also, there were regional differences in the age effect on brain stiffness. Concerning demented patients, differential patterns of stiffness were found for distinct dementia subtypes. Alzheimer''s disease and frontotemporal dementia exhibited decreased brain stiffness in comparison to cognitively healthy controls and significant declines were found in regions known to be affected by the disease. In normal pressure hydrocephalus, the results were not consistent across studies, and in dementia with Lewy bodies no significant differences in brain stiffness were found. In conclusion, aging is characterized by the softening of brain tissue and this event is even more pronounced in pathological aging, such as dementia. MRE technique could be applied as a sensible diagnostic tool to identify deviations from normal aging and develop new brain biomarkers of cognitive decline/dementia that would help promote healthier cognitive aging.     

The effects of a high-fat sucrose diet on functional outcome following cortical contusion injury in the rat

Traumatic brain injury (TBI) is a major public health issue affecting 1.7 million Americans each year, of which approximately 50,000 are fatal. High-fat sucrose (HFS) diets are another public health issue which can lead to obesity, hypertension, and many other debilitating disorders. These two disorders combined can lead to more complicated issues. It has recently been shown that HFS diets can reduce levels of brain-derived neurotrophic factor (BDNF) leading to reductions in neuronal and behavioral plasticity. This reduction in BDNF is suspected of increasing the susceptibility of the brain to injury. To test the effects of a HFS diet on recovery of function post-TBI, male Sprague-Dawley rats were used in this study. Eight weeks prior to TBI, rats were placed on a special HFS diet (n = 14) or a standard rodent diet (n = 14). Following this eight-week period, rats were prepared with bilateral frontal cortical contusion injuries (CCI) or sham procedures. Beginning two days post-TBI, animals were tested on a battery of behavioral tests to assess somatosensory dysfunction and spatial memory in the Morris water maze, with a reference memory and a working memory task. Following testing, animals were sacrificed and their brains processed for lesion analysis. The HFS diet worsened performance on the bilateral tactile adhesive removal test in sham animals. Injured animals on the Standard diet had a greater improvement in somatosensory performance in the adhesive removal test and had better performance on the working memory task compared to animals on the HFS diet. The HFS diet also resulted in significantly greater loss of cortical tissue post-CCI than in the Standard diet group. This study may aid in determining how nutritional characteristics or habits interact with damage to the brain.     

Normobaric oxygen worsens outcome after a moderate traumatic brain injury

Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n=8) or normal air (n=8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI.     

Widespread and lateralized effects of acute traumatic brain injury on norepinephrine turnover in the rat brain

Norepinephrine (NE) has been implicated in recovery of function following traumatic brain injury (TBI). While bilateral decreases in brain NE turnover occur at 6–24 h after TBI, it is unknown what effects unilateral TBI might have on brain NE turnover over the first few minutes after injury. Here male Sprague-Dawley rats had unilateral contusions of either the right or left somatosensory cortex produced by an air driven piston. At 30min after TBI, brain NE turnover was assessed by measuring the ratio of 3-methoxy-4-hydroxyphenylglycol (MHPG) to NE levels in various brain regions. Both right and left TBI produced 32–103% increases in NE turnover at the injury site and in the ipsilateral cerebral cortex surrounding, rostral and caudal to the injury as compared to the contralateral, uninjured site or to the homologous sites in uninjured controls. NE turnover was also altered selectively in some brain areas not affected by right TBI. Left TBI decreased NE turnover by 29% in the frontal cortex contralateral to the injury and by 24% bilaterally in the hypothalamus while increasing locus coeruleus NE turnover by 72% compared to uninjured controls. Thus, unilateral cortical TBI produced predominantly ipsilateral increases in cortical NE turnover but variable, bilateral changes in NE turnover in subcortical areas which were dependent upon the side of injury. These subcortical differences may explain some of the lateralized effects of cortical injury on post-injury behavior.     

Effects of enoxaparin in the rat hippocampus following traumatic brain injury

Purpose of this study was to investigate the effects of low molecular weight heparin, enoxaparin, on different parameters of the hippocampal damage following traumatic brain injury (TBI) in the rat. TBI of moderate severity was performed over the left parietal cortex using the lateral fluid percussion brain injury model. Animals were s.c. injected with either enoxaparin (1 mg/kg) or vehicle 1, 7, 13, 19, 25, 31, 37, and 43 h after the TBI induction. Sham-operated, vehicle-treated animals were used as the control group. Rats were sacrificed 48 h after the induction of TBI. Hippocampi were processed for spectrophotometric measurements of the products of oxidative lipid damage, thiobarbituric acid-reactive substances (TBARS) levels, as well as the activities of antioxidant enzymes, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Moreover, the Western blotting analyses of the oxidized protein levels, expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), pro- and mature-interleukin-1β (pro-, and mature-IL-1β), and active caspase-3 were performed. COX-2 expressions were also explored by using immunohistochemistry. Glial fibrillary acidic protein immunochistochemistry was performed with the aim to assess the level of astrocytic activity. Fluoro-Jade B staining was used to identify the level and extent of hippocampal neuronal injury. TBI caused statistically significant increases of the hippocampal TBARS and oxidized protein levels as well as COX-2, pro-IL-1β, and active caspase-3 overexpressions, but it did not significantly affect the SOD and GSH-Px activities, the iNOS, and mature-IL-1β expression levels. TBI also induced hippocampal reactive astrocytosis and neurodegeneration. Enoxaparin significantly decreased the hippocampal TBARS and oxidized protein levels, COX-2 overexpression and reactive gliosis, but it did not influence the SOD and GSH-Px activities, pro-IL-1β and active caspase-3 overexpressions as well as neurodegeneration following TBI. These findings demonstrate that enoxaparin may reduce oxidative damage, inflammation and astrocytosis following TBI in the rat and could be a candidate drug for neuroprotective treatment of this injury.     

Salvianolic acid B attenuates brain damage and inflammation after traumatic brain injury in mice

Salvianolic acid B (SalB), a bioactive compound isolated from the Chinese medicinal herb Danshen, has been shown to exert various anti-oxidative and anti-inflammatory activities in in vitro and in vivo studies. Here, we investigated the protective effects of SalB on traumatic brain injury (TBI) in mice. When administered within 2 h after TBI onset, SalB (25 mg/kg) reduced brain edema, lesion volume and motor functional deficits, and improved spatial learning and memory abilities. Moreover, SalB treatment inhibited the neutrophil infiltration and microglial activation at 48 h after TBI. Enzyme-linked immunosorbent assay (ELISA) for brain tissue homogenates was performed at 24 h after TBI to evaluate the expression of inflammation-related cytokines. The results showed that SalB suppressed the expression of pro-inflammatory cytokines TNF-α and IL-1β, whereas enhanced the expression of anti-inflammatory cytokines IL-10 and TGF-β1. All of these findings extended the protective role of SalB in the model of TBI and suggested that these protective effects might be associated with its anti-inflammatory activities. Thus SalB may have therapeutic potential for patients with TBI and perhaps other forms of acute brain injury.     

Serum soluble CD40 Ligand levels are associated with severity and mortality of brain trauma injury patients

Background

Serum soluble CD40 Ligand (sCD40L) levels, which exhibit prothrombotic and proinflammatory properties, have not been studied in patients with traumatic brain injury (TBI). Thus, the objective of this study was to determine whether serum sCD40L levels are associated with severity and mortality in patients with severe TBI.

Methods

This was a prospective, observational and multicenter study carried out in six Spanish Intensive Care Units. Patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9 were included, while those with Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Serum levels of sCD40L were measured on the day of TBI. Endpoint was established in 30-day mortality.

Results

We found higher serum sCD40L levels (P < 0.001) in non-surviving TBI patients (N = 27) than in survivor ones (N = 73). Logistic regression analysis showed that serum sCD40L levels were associated with 30-day mortality (OR = 1.58; 95% CI = 1.12-2.21; P = 0.008) controlling for APACHE-II score and computer tomography findings. The area under the curve (AUC) for serum sCD40L levels as predictor of 30-day mortality was 0.79 (95% CI = 0.70-0.86; P < 0.001). Survival analysis showed that patients with serum sCD40L levels higher than 2.11 ng/mL presented increased 30-day mortality than patients with lower levels (Hazard ratio = 9.0; 95% CI = 4.25-19.27; P < 0.001). We found an association between serum sCD40L levels and APACHE-II (rho = 0.33; P = 0.001), and GCS score (rho = -0.21; P = 0.04).

Conclusions

To our knowledge, this is the first study reporting data on serum sCD40L levels in patients with severe TBI. The most relevant and newer findings of our study are that serum sCD40L levels in non-surviving patients with severe TBI are higher than in surviving ones, and that there are an association between serum sCD40L levels and TBI severity and mortality.     

Quantitative T2 mapping as a potential marker for the initial assessment of the severity of damage after traumatic brain injury in rat

Severity of traumatic brain injury (TBI) positively correlates with the risk of post-traumatic epilepsy (PTE). Studies on post-traumatic epileptogenesis would greatly benefit from markers that at acute phase would reliably predict the extent and severity of histologic brain damage caused by TBI in individual subjects. Currently in experimental models, severity of TBI is determined by the pressure of applied load that does not directly reflect the extent of inflicted brain injury, mortality within experimental population, or impairment in behavioral tests that are laborious to perform. We aimed to compare MRI markers measured at acute post-injury phase to previously used indicators of injury severity in the ability to predict the extent of histologically determined post-traumatic tissue damage. We used lateral fluid-percussion injury model in rat that is a clinically relevant model of closed head injury in humans, and results in PTE in severe cases. Rats (48 injured, 12 controls) were divided into moderate (mTBI) and severe (sTBI) groups according to impact strength. MRI data (T2, T2*, lesion volume) were acquired 3 days post-injury. Motor deficits were analysed using neuroscore (NS) and beam balance (BB) tests 2 and 3 days post-injury, respectively. Histological evaluation of lesion volume (Fluoro-Jade B) was used as the reference outcome measure, and was performed 2 weeks after TBI. From MRI parameters studied, quantitative T2 values of cortical lesion not only correlated with histologic lesion volume (P < 0.001, r = 0.6, N = 34), as well as NS (P < 0.01, r = − 0.5, N = 34) and BB (P < 0.01, r = − 0.5, N = 34) results, but also successfully differentiated animals with mTBI from those with sTBI 70.6 ± 6.2 6.2 ms vs. 75.9 ± 2.6 ms, P < 0.001). Quantitative T2 of the lesion early after TBI can serve as an indicator of the severity of post-traumatic cortical damage and neuro-motor impairment, and has a potential as a clinical marker for identification of individuals with elevated risk of PTE.     

The pathophysiology of traumatic brain injury in alpha7 nicotinic cholinergic receptor knockout mice

The alpha7 nicotinic cholinergic receptor is a ligand-gated ion channel with calcium permeability similar to that of ionotrophic glutamate receptors. Previous studies from our laboratory have implicated changes in expression alpha7 nicotinic cholinergic receptors in the pathophysiology of traumatic brain injury (TBI). In rats, TBI causes a time-dependent and significant decrease in cortical and hippocampal alpha-[(125)I]-bungarotoxin (BTX) binding. We have postulated that deficits in alpha7 expression may contribute to TBI-induced cognitive impairment and that nicotinic receptor agonists can reverse alpha7 binding deficits and result in significant cognitive improvement compared to saline-treated controls. Thus, alpha7 nAChRs could be involved in a form of cholinergically mediated excitotoxicity following brain injury. In the current study, wild-type, heterozygous and null mutant mice were employed to test the hypothesis that genotypic depletion of the alpha7 receptor would render animals less sensitive to tissue loss and brain inflammation following experimental brain injury. Mice were anesthetized and subjected to a 0.5-mm cortical contusion injury of the somatosensory cortex. Brain inflammation, changes in nicotinic receptor expression and cortical tissue sparing were evaluated in wild-type, heterozygous and homozygous mice 1 week following TBI. In wild-type mice, brain injury caused a significant decrease in BTX binding in several hippocampal regions, consistent with what we have measured in rat brain following TBI. However, there were no genotypic differences in cortical tissue sparing or brain inflammation in this experiment. Although the results of this study were largely negative, it is still plausible that changes in the activity/expression of native alpha7 receptors contribute to pathophysiology following TBI. However, when null mutant mice develop in the absence of central alpha7 expression, it is possible that compensatory changes occur that confound the results obtained.     

Comparison of rat sensory behavioral tasks to detect somatosensory morbidity after diffuse brain-injury

Brain injury disrupts neuronal circuits, impacting neurological function. Selective and sensitive behavioral tests are required to explore neurological dysfunction, recovery and potential therapy. Previously we reported that the Whisker Nuisance Task (WNT), where whiskers are manually stimulated in an open field, shows sensory sensitivity in diffuse brain-injured rats. To further explore this somatosensory morbidity, we evaluated three additional whisker-dependent tasks: Gap Cross Test, a novel Angle Entrance Task and Whisker Guided Exploration Task. Brain-injured (n = 11) and sham (n = 8) rats were tested before midline fluid percussion brain injury (moderate: 2.0 atm) and 1 and 4 weeks after injury. For the WNT, we confirmed that brain-injured rats develop significant sensory sensitivity to whisker stimulation over 28 days. In the Gap Cross Test, where rats cross progressively larger elevated gaps, we found that animals were inconsistent in crossable distance regardless of injury. In the Angle Entrance Task, where rats enter 30°, 40°, 50° or 80° corners, rats performed consistently regardless of injury. In the Whisker Guided Exploration Task, where rats voluntarily explore an oval circuit, we identified significant decreases in the number of rears and reversals and changes in the predominant location (injured rats spend more time in the inside of the turn compared to the outside) after injury and increased thigmotaxis after sham and brain-injury. Both the WNT and Whisker Guided Exploration Task show injury-induced somatosensory behavioral morbidity; however, the WNT remains more sensitive in detecting brain injury, possibly due to imposed whisker stimulation that elicits agitation similar to the human condition.     

Behavioral, electrophysiological, and histopathological consequences of mild fluid-percussion injury in the rat

Metabolic dysfunction in the relay nuclei of the rat vibrissa circuit follows traumatic brain injury (TBI). This study examined the effects of mild (1.4–1.5 atm) parasagittal fluid-percussion injury on the elctrophysiology of this circuit. TBI caused significant reductions in slope and increases in latency of vibrissa-evoked field potentials 3 days after injury. Assessment of open-field swimming revealed an increase in thigmotaxis 2 days after injury. TBI caused mild selective cortical damage and limited axonal swelling at the injury site. Thus mild injury disrupts somatosensory electrophysiology and exploratory behavior.     

Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma

Objective

Severe traumatic brain injury (TBI) has a major role in mortality rate among the other types of trauma. The aim of this clinical study was to assess the effect of progesterone on the improvement of neurologic outcome in patients with acute severe TBI.

Methods

A total of 76 patients who had arrived within 8 h of injury with a Glasgow Coma Score ≤8 were enrolled in the study. In a randomized style 38 received progesterone (1 mg/kg per 12 h for 5 days) and 38 did not.

Results

There was a better recovery rate and GOS score for the patients who were given progesterone than for those in the control group in a 3-months follow-up period (50% vs. 21%); subgroup analysis showed a significant difference in the percentage of favorable outcome between the two groups with GCS of 5–8 (p = 0.03).

Conclusion

The use of progesterone may significantly improve neurologic outcome of patients suffering severe TBI up to 3 months after injury, especially those with 5 ≤ GCS ≤ 8, providing a potential benefit to the treatment of acute severe TBI patients. Considering this drug had no significant side effects, so progesterone could be used in patients with severe TBI as a neuro-protective drug.     

Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury

A prospective, multicenter, randomized trial did not demonstrate improved outcomes in severe traumatic brain injured patients treated with mild hypothermia [Clifton, G.L., Miller, E.R., Choi, S.C., Levin, H.S., McCauley, S., Smith, K.R., Jr., Muizelaar, J.P., Wagner, F.C., Jr., Marion, D.W., Luerssen, T.G., Chesnut, R.M., Schwartz, M., 2001. Lack of effect of induction of hypothermia after acute brain injury. N. Engl. J. Med. 344, 556-563.]. However, the mean time to target temperature was over 8 h and patient inclusion was based on Glasgow Coma Scale score so brain pathology was likely diverse. There remains significant interest in the benefits of hypothermia after traumatic brain injury (TBI) and, in particular, traumatic axonal injury (TAI), which is believed to significantly contribute to morbidity and mortality of TBI patients. The long-term beneficial effect of mild hypothermia on TAI has not been established. To address this issue, we developed an in vivo rat optic nerve stretch model of TAI. Adult male Sprague-Dawley rats underwent unilateral optic nerve stretch at 6, 7 or 8 mm piston displacement. The increased number of axonal swellings and bulbs immunopositive for non-phosphorylated neurofilament (SMI-32) seen four days after injury was statistically significant after 8 mm displacement. Ultrastructural analysis 2 weeks after 8 mm displacement revealed a 45.0% decrease (p < 0.0001) in myelinated axonal density in the optic nerve core. There was loss of axons regardless of axon size. Immediate post-injury hypothermia (32 °C) for 3 h reduced axonal degeneration in the core (p = 0.027). There was no differential protection based on axon size. These results support further clinical investigation of temporally optimized therapeutic hypothermia after traumatic brain injury.     

Does hypofrontality expand to global brain area in progression of schizophrenia?: A cross-sectional study between first-episode and chronic schizophrenia

Although to date there have been no conclusive pathophysiological findings in support of the degenerative theory of the etiology of schizophrenia, the results of neuroimaging studies have suggested that progressive changes in the brain do occur during the clinical course of schizophrenia. However, there has been no report on alterations in regional cerebral blood flow (rCBF) under resting condition, which was compared between the first-episode and the chronic patients of schizophrenia and healthy controls. Therefore, in this study, we applied three-dimensional stereotactic surface projection analysis of resting SPECT (3D-SSP SPECT) in patients with first-episode (n = 18) and chronic schizophrenia (n = 23) and age-/sex-matched healthy controls (n = 40). The rCBFs in the middle/inferior/medial frontal gyrus and the anterior cingulate gyrus were significantly decreased in both patient groups, relative to the respective controls (Z > 3.0, P < 0.001, uncorrected). The chronic group showed significant hypoperfused region in the left inferior parietal lobule and middle/inferior temporal gyrus. Furthermore, within-cases comparison between the first-episode and chronic schizophrenia, revealed that the significant hypoperfused regions in the chronic group, compared to the first-episode group, were not only the lateral and medial prefrontal cortex, but also the inferior parietal cortex, posterior part of the temporal lobe, and the cuneus. The present study suggested that the reduction in rCBF occurs in the posterior brain area in addition to the frontal lobe across all clinical stages of schizophrenia.     

Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS

Background

Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics.

Objective

This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS).

Methods

99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10 Hz) left-side stimulation in 33 patients, and low frequency (1 Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p < 0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation.

Results

Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p = 0.017) or right stimulation (p < 0.001), without significant perfusion differences between these two subgroups.

Conclusions

These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group.     

The effects of cyclosporin-A on axonal conduction deficits following traumatic brain injury in adult rats

Immunophilin ligands, including cyclosporin-A (CsA), have been shown to be neuroprotective in experimental models of traumatic brain injury (TBI) and to attenuate the severity of traumatic axonal injury. Prior studies have documented CsA treatment to reduce essential components of posttraumatic axonal pathology, including impaired axoplasmic transport, spectrin proteolysis, and axonal swelling. However, the effects of CsA administration on axonal function, following TBI, have not been evaluated. The present study assessed the effects of CsA treatment on compound action potentials (CAPs) evoked in corpus callosum of adult rats following midline fluid percussion injury. Rats received a 20 mg/kg bolus of CsA, or cremaphor vehicle, at either 15 min or 1 h postinjury, and at 24 h postinjury CAP recording was conducted in coronal brain slices. To elucidate how injury and CsA treatments affect specific populations of axons, CAP waveforms generated largely by myelinated axons (N1) were analyzed separately from the CAP signal, which predominantly reflects activity in unmyelinated axons (N2). CsA administration at 15 min postinjury resulted in significant protection of CAP area, and this effect was more pronounced in N1, than in the N2, CAP component. This treatment also significantly protected against TBI-induced reductions in high-frequency responding of the N1 CAP signal. In contrast, CsA treatment at 1 h did not significantly protect CAPs but was associated with atypical waveforms in N1 CAPs, including decreased CAP duration and reduced refractoriness. The present findings also support growing evidence that myelinated and unmyelinated axons respond differentially to injury and neuroprotective compounds.     

Gender- and age-dependent changes in nucleoside levels in the cerebral cortex and white matter of the human brain

Nucleosides are neuromodulators that participate in various neuronal functions in the brain. In previous studies, we described regional differences in the concentrations of nucleosides and their derivatives in the human brain. To better understand the functions of nucleosides in the central nervous system, we investigated gender- and age-dependent changes in the levels of nucleosides and their metabolites. The concentrations of uridine, inosine, guanosine and adenosine as well as uracil, hypoxanthine and xanthine were measured in the frontal cortex and white matter of post-mortem brain tissue samples of middle-aged and old men as well as women. The average in vivo concentrations calculated from the 40 samples investigated (regardless of anatomical locations, gender or age; mean ± S.E.M.) were as follows (pmol/mg wet tissue weight): 9.7 ± 0.8 adenosine, 85.8 ± 3.9 inosine, 14.3 ± 0.9 guanosine, 37.3 ± 1.8 uridine, 8.9 ± 0.6 uracil, 63.3 ± 2.1 hypoxanthine and 38.7 ± 1.5 xanthine. We conclude that concentration differences between uridine, inosine, guanosine and adenosine in the frontal cortex and cerebral white matter suggest that nucleoside metabolism is altered with aging and regulated differently between men and women.     

Somatosensory-motor bodily representation cortical thinning in Tourette: Effects of tic severity, age and gender

Introduction

Tourette syndrome (TS) implicates the disinhibition of the cortico-striatal-thalamic-cortical circuitry (CSTC). Previous studies used a volumetric approach to investigate this circuitry with inconsistent findings. Cortical thickness may represent a more reliable measure than volume due to the low variability in the cytoarchitectural structure of the grey matter.

Methods

66 magnetic resonance imaging scans were acquired from 34 TS subjects (age range 10-25, mean 17.19 ± 4.1) and 32 normal controls (NC) (age range 10-20, mean 16.33 ± 3.56). Brain morphology was assessed using the fully automated CIVET pipeline at the Montreal Neurological Institute.

Results

We report (1) significant cortical thinning in the fronto-parietal and somatosensory-motor cortices in TS relative to NC (p < .05); (2) TS boys showed thinner cortex relative to TS girls in the fronto-parietal cortical regions (p < .05); (3) significant decrease in the fronto-parietal mean cortical thickness in TS subjects with age relative to NC and in the pre-central cortex in TS boys relative to TS girls; (4) significant negative correlations between tic severity and the somatosensory-motor cortical thickness.

Conclusions

TS revealed important thinning in brain regions particularly involved in the somatosensory/motor bodily representations which may play an important role in tics. Our findings are in agreement with Leckman et al. (1991) hypothesis stating that facial tics would be associated with dysfunction in an orofacial subset of the motor circuit, eye blinking with the occulo-motor circuit, whereas lack of inhibition to a dysfunction in the prefrontal cortex. Gender and age differences may reflect differential etiological factors, which have significant clinical relevance in TS and should be considered in developing and using diagnostic and therapeutic interventions.     

Cerebral blood flow changes after brain injury in human amyloid-beta knock-in mice

Traumatic brain injury (TBI) is an environmental risk factor for Alzheimer''s disease (AD). Increased brain concentrations of amyloid-β (Aβ) peptides and impaired cerebral blood flow (CBF) are shared pathologic features of TBI and AD and promising therapeutic targets. We used arterial spin-labeling magnetic resonance imaging to examine if CBF changes after TBI are influenced by human Aβ and amenable to simvastatin therapy. CBF was measured 3 days and 3 weeks after controlled cortical impact (CCI) injury in transgenic human Aβ-expressing APP^NLh/NLh mice compared to murine Aβ-expressing C57Bl/6J wild types. Compared to uninjured littermates, CBF was reduced in the cortex of the injured hemisphere in both Aβ transgenics and wild types; deficits were more pronounced in the transgenic group, which exhibited injury-induced increased concentrations of human Aβ. In the hemisphere contralateral to CCI, CBF levels were stable in Aβ transgenic mice but increased in wild-type mice, both relative to uninjured littermates. Post-injury treatment of Aβ transgenic mice with simvastatin lowered brain Aβ concentrations, attenuated deficits in CBF ipsilateral to injury, restored hyperemia contralateral to injury, and reduced brain tissue loss. Future studies examining long-term effects of simvastatin therapy on CBF and chronic neurodegenerative changes after TBI are warranted.     

Rearrangement of motor centers and its relationship to the neurological status of low-grade glioma examined on pre- and postoperative fMRI

Objective

Well-developed compensatory mechanisms, based on the phenomenon of brain plasticity, exist in patients with neuroepithelial tumors, especially with highly differentiated gliomas (WHO grade II). We studied phenomenon of rearrangement of sensorimotor cortex using functional magnetic resonance imaging (fMRI), and verified relationship between observed changes and results of neurological and neuropsychological assessment.

Methods

Study group included 20 patients with WHO grade II gliomas located within motor or sensory cortex. fMRI examination, as well as clinical, neurological (Karnofsky performance score [KPS] and Lovett's scale [Lo]), and neuropsychological assessment (Digit Coding Symbol Test and Digit Span Test) were performed pre-operatively and 3 months post-surgery.

Results

There were no significant differences in pre- and postoperative performance status of patients. Although statistically insignificant, an increase in frequency of activation of primary and secondary cortical motor centers was observed postoperatively (p > 0.05). Prior to surgery, motor centers were characterized by lower values of t-statistics than in postoperative period (p > 0.05). In contrast, values of parameters describing the size of examined centers, i.e. mean number of clusters, were lower, but not statistically significant on postoperative examination (p > 0.05). Compared to individuals without motor deficit, patients with preoperative Lo3/Lo4 paralysis showed significantly higher mean values of t-statistics in the accessory motor area on postoperative examination (p < 0.05).

Conclusions

The processes of motor cortex rearrangement seemed to be associated with the pre- and postoperative neurological and neuropsychological status of patients. After contralateral primary motor cortex, accessory motor area was the second most frequently activated center, both pre- and postoperatively.