Cerebral Palsy

We tested the idea that real-world situations, such as the highly strenuous exercise involved in marathon running, that impose extreme physical demands on an individual may result in neurohormonal changes that alter the functioning of memory. Marathon runners were given implicit and explicit memory tasks before or immediately after they completed a marathon. Runners tested immediately upon completing the marathon showed impairment in the explicit memory task but enhancement in the implicit memory task. This postmarathon impairment in explicit memory is similar to that seen with amnesic patients with organic brain damage. However, no previous studies have shown a simultaneous enhancement in the implicit memory task, as shown by the marathon runners in the present study. This study indicates that human memory functioning can be dynamically altered by such activities as marathon running, in which hundreds of thousands of healthy normal individuals routinely partake.

The steroidal regulation of vertebrate neuroanatomy and neurophysiology includes a seemingly unending list of brain areas, cellular structures and behaviors modulated by these hormones. Estrogens, in particular have emerged as potent neuromodulators, exerting a range of effects including neuroprotection and perhaps neural repair. In songbirds and mammals, the brain itself appears to be the site of injury-induced estrogen synthesis via the rapid transcription and translation of aromatase (estrogen synthase) in astroglia. This induction seems to occur regardless of the nature and location of primary brain damage. The induced expression of aromatase apparently elevates local estrogen levels enough to interfere with apoptotic pathways, thereby decreasing secondary degeneration and ultimately lessening the extent of damage. There is even evidence suggesting that aromatization may affect injury-induced cytogenesis. Thus, aromatization in the brain appears to confer neuroprotection by an array of mechanisms that involve the deceleration and acceleration of degeneration and repair respectively. We are only beginning to understand the factors responsible for the injury-induced transcription of aromatase in astroglia. In contrast, much of the manner in which local and circulating estrogens may achieve their neuroprotective effects has been elucidated. However, gaps in our knowledge include issues about the cell-specific regulation of aromatase expression, steroidal influences of aromatization distinct from estrogen formation, and questions about the role of constitutive aromatase in neuroprotection. Here we describe the considerable consensus and some interesting differences in knowledge gained from studies conducted on diverse animal models, experimental paradigms and preparations towards understanding the neuroprotective actions of brain aromatase.

We report a functional magnetic resonance imaging (fMRI) adaptation study of two well-described patients, DF and PS, who present face identity recognition impairments (prosopagnosia) following brain-damage. Comparing faces to non-face objects elicited activation in all visual areas of the cortical face processing network that were spared subsequent to brain damage. The common brain lesion in the two patients was in the right inferior occipital cortex, in the territory of the right “occipital face area” (‘OFA’), which strengthens the critical role of this region in processing faces. Despite the lesion to the right ‘OFA’, there was normal range of sensitivity to faces in the right “fusiform face area” (‘FFA’) in both patients, supporting a non-hierarchical model of face processing at the cortical level. At the same time, however, sensitivity to individual face representations, as indicated by release from adaptation to identity, was abnormal in the right ‘FFA’ of both patients. This suggests that the right ‘OFA’ is necessary to individualize faces, perhaps through reentrant interactions with other cortical face sensitive areas. The lateral occipital area (LO) is damaged bilaterally in patient DF, who also shows visual object agnosia. However, in patient PS, in whom LO was spared, sensitivity to individual representations of non-face objects was still found in this region, as in the normal brain, consistent with her preserved object recognition abilities. Taken together, these observations, which fruitfully combine functional imaging and neuropsychology, place strong constraints on the possible functional organization of the cortical areas mediating face processing in the human brain.

Each year, between 1.6×10(6) and 3.8×10(6) concussions are sustained by athletes playing sports, with football having the highest incidence. The high number of concussions in football provides a unique opportunity to collect biomechanical data to characterize mild traumatic brain injury. Human head acceleration data for a range of impact severities were collected by instrumenting the helmets of collegiate football players with accelerometers. The helmets of ten Virginia Tech football players were instrumented with measurement devices for every game and practice for the 2007 football season. The measurement devices recorded linear and angular accelerations about each of the three axes of the head. Data for each impact were downloaded wirelessly to a sideline data collection system shortly after each impact occurred. Data were collected for 1712 impacts, creating a large and unbiased data set. While a majority of the impacts were of relatively low severity (<30 g and <2000 rad/s(2)), 172 impacts were greater than 40 g and 143 impacts were greater than 3000 rad/s(2). No instrumented player sustained a clinically diagnosed concussion during the 2007 season. A large and unbiased data set was compiled by instrumenting the helmets of collegiate football players. Football provides a unique opportunity to collect head acceleration data of varying severity from human volunteers. The addition of concurrent concussive data may advance the understanding of the mechanics of mild traumatic brain injury. With an increased understanding of the biomechanics of head impacts in collegiate football and human tolerance to head acceleration, better equipment can be designed to prevent head injuries.

This study assesses the feasibility of using a multiperturbation analysis (MPA) approach for lesion-symptom mapping. We analyze the relative contribution of damage in different brain regions to the expression of spatial neglect, as revealed in line-bisection performance. The data set comprised of normalized lesion information and bisection test results from 23 first-event right-hemisphere stroke patients. Obtaining quantitative measures of task relevance for different regions of interest (ROIs), the following ROIs were found to be the most contributing: the supramarginal and angular gyri of the inferior parietal lobule, the superior parietal lobule, the anterior part of the temporo-parietal junction connecting the superior temporal and supramarginal gyri, and the thalamus. MPA is likely to play an important role in elucidating the anatomical substrate of complex functions. Hum Brain Mapp, 2009. (c) 2009 Wiley-Liss, Inc.

In a wide variety of acute and chronic central nervous system (CNS) disorders, inflammatory processes contribute to the damage of brain cells and progression of the disease. Along with other regulatory cytokines, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is involved in the pathology of multiple sclerosis (MS) and murine experimental autoimmune encephalomyelitis (EAE), bacterial meningitis (BM), HIV encephalitis (HIVE), stroke and Alzheimer’s disease (AD). In these conditions, TRAIL is released within the brain mainly by activated microglia and leukocytes infiltrating from the blood stream. TRAIL promotes apoptosis of parenchymal cells in MS/EAE, HIVE, AD and stroke through interaction with TRAIL death receptors expressed on these cells. Frequently, cells in the diseased brain display increased susceptibility to apoptosis induction by TRAIL due to upregulation of death receptors and downregulation of decoy receptors. On the other hand, TRAIL inhibits the proliferation of encephalitogenic T cells in EAE, and it is involved in the clearance of infected brain macrophages in HIVE and of activated neutrophils in BM by interaction with their death receptors. Especially in BM, the ability of TRAIL to limit an acute granulocyte-driven inflammation carries significant neuroprotective potential. Given the diversity of beneficial and harmful effects in the immune and nervous system, TRAIL is a double-edged sword in diseases involving CNS inflammation.

Objective This report aims to describe the oxidative damage profile in brain of presenilin1 and presenilin2 conditional double knockout mice (dKO) at both early and late age stages, and to discuss the correlation between oxidative stress and the Alzheimer-like phenotypes of dKO mice. Methods The protein level of Abeta(42) in dKO cortex and free 8-OHdG level in urine were measured by ELISA. Thiobarbituric acid method and spectrophotometric DNPH assay were used to determine the lipid peroxidation and protein oxidation in cortex, respectively. SOD and GSH-PX activities were assessed by SOD Assay Kit-WST and GSH-PX assay kit, separately. Results Significant decrease of Abeta(42) was verified in dKO cortex at 6 months as compared to control mice. Although lipid peroxidation (assessed by MDA) was increased only in dKO cortex at 3 months and protein oxidation (assessed by carbonyl groups) was basically unchanged in dKO cortex, ELISA analysis revealed that free 8-OHdG, which was an indicator of DNA lesion, was significantly decreased in urine of dKO mice from 3 months to 12 months. Activities of SOD and GSH-PX in dKO and control cortices showed no statistical difference except a significant increase of GSH-PX activity in dKO mice at 9 months. Conclusion Oxidative damage, especially DNA lesion, was correlated with the neurodegenerative symptoms that appeared in dKO mice without the deposition of Abeta(42). Triggers of oxidative damage could be the inflammatory mediators released by activated microglia and astrocytes.

The authors examine the relationship of the two signature injuries experienced by military personnel serving in Afghanistan and Iraq: posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mild TBI). Studies show that a substantial minority of those serving develop persistent emotional sequelae (such as PTSD and other psychological health problems) and/or somatic or cognitive sequelae (postconcussive symptoms) of traumatic exposure. Remarkably, the mechanism (emotional versus biomechanical) and locus (head versus other regions) of injury are weak determinants of whether an individual develops PTSD, persistent postconcussive symptoms, or both. Preexisting or traumatically acquired cognitive dysfunction can increase the risk for these syndromes, probably by reducing cognitive reserve. Structural and functional neuroimaging studies can be interpreted to explain part of the shared symptomatic and functional variance in these syndromes, but this literature is far from consistent and serves mainly to raise new, challenging questions about mutual pathophysiology. The frequent confluence of PTSD and persistent postconcussive symptoms in military personnel strains the bounds of these constructs. New studies are needed to improve our understanding of how emotional and biomechanical stressors can yield these adverse outcomes and how such outcomes can be prevented and treated.

To explore knowledge and management of childhood fever among ethnically diverse parents and identify opportunities for educational intervention, we administered a cross-sectional survey to a convenience sample of 487 parents of children enrolled in 2 urban hospital-based pediatric clinics. Outcomes included parental definition of fever, level of concern, and management of fever. Latino parents were least likely to identify a temperature as nonfebrile from 97-100.3 degrees F (adjusted odds ratios [aOR] 0.06) or identify a fever as a temperature from 100.4-107 degrees F (aOR 0.52). african americans were least likely to believe that fever can cause death or brain damage (aOR 0.4). african americans were more likely to dose ibuprofen more frequently than recommended (aOR 1.97). all ethnicities are equally likely to treat normal temperatures and dose acetaminophen too frequently. Therefore continued education of all families about fever is necessary, and there are opportunities to develop ethnically sensitive strategies to target educational interventions.

Rho kinases (ROCK) are serine/threonine kinases that play an important role in fundamental processes of cell migration, proliferation and survival. Blockade of ROCK promotes axonal regeneration and neuroprotection, thereby exhibiting therapeutic potentials for clinical application to spinal cord damage and stroke. Here we explored the mechanisms of Fasudil, a ROCK inhibitor, in neuroprotection and neurogenesis by using oxygen glucose deprivation (OGD) as an in vitro ischemia model. Fasudil stimulates astrocytes to produce granulocyte colony-stimulating factor (G-CSF). Astrocyte-conditioned medium treated with Fasudil (ACM-F) contributes to the generation of neurospheres, and decreases neuron death. Neutralization of G-CSF in ACM-F and blocking of G-CSF receptor in neuronal cell cultures revealed that Fasudil-induced neuroprotection and/or neurogenesis are mediated partially through astrocyte-derived G-CSF. Our results indicate that ROCK inhibition by Fasudil, protecting neurons and mobilizating neural stem cells, might represent a useful therapeutic perspective for various neurological disorders characterized by neuron death.