Cerebral Palsy

This study aims to characterize the interaction of explosive blast waves through simulated anatomical systems. We have developed physical models and a systematic approach for testing traumatic brain injury (TBI) mechanisms and occurrences. A simplified series of models consisting of spherical Poly(methyl methacrylate) (PMMA) shells housing synthetic gelatins as brain simulants have been utilized. A series of experiments was conducted to compare the sensitivity of the system response to mechanical properties of the simulants under high strain-rate explosive blasts. Small explosive charges were directed at the models to produce a realistic blast wave in a scaled laboratory setting. Blast profiles were measured and analyzed to compare system response severity. High-speed shadowgraph imaging captured blast wave interaction with the head model while particle tracking captured internal response for displacement and strain correlation. The results suggest amplification of shock waves inside the head near material interfaces due to impedance mismatches. In addition, significant relative displacement was observed between the interacting materials suggesting large strain values of nearly 5%. Further quantitative results were obtained through shadowgraph imaging of the blasts confirming a separation of time scales between blast interaction and bulk movement. These results lead to a conclusion that primary blast effects may potentially contribute significantly to the occurrence of military associated TBI. Copyright © 2010. Published by Elsevier Inc.

Reactive oxygen species (ROS) are mediators of brain injury in ischemia/reperfusion. An involvement of the NADPH oxidase Nox2 has been demonstrated. In contrast, only little is known about the contribution of the Nox1 homologue in this context. Thus, we studied the role of Nox1 in early cerebral reperfusion injury in the middle cerebral artery filament occlusion model using Nox1 knockout mice. Genetic deletion of a functional Nox1 lead to a 55% attenuation in lesion size at 24h after induction of 1h ischemia (p<0.05). This result was paralleled by a significant improvement of neurological outcome, preservation of blood-brain-barrier integrity and reduced cerebral edema in Nox1(y/-)compared to WT mice. Interestingly, no difference in infarct size between WT and Nox1(y/-) was observed with an occlusion time of 2 hours and longer. Apoptosis rate as measured by TUNEL staining was similar between the groups. Moreover, infusion of the antioxidant TEMPOL as well as of the unspecific NO-synthase inhibitor L-NAME elicited similar changes with respect to ischemic tissue damage between WT and Nox1-deficient mice. In conclusion, Nox1 is involved in the pathophysiology of cerebral ischemia. Our data however indicate that ROS-mediated direct cellular injury is unlikely to explain the protective effect achieved by genetic deletion of the enzyme. Copyright © 2010. Published by Elsevier Inc.

FLOODY, O. R., L. OUDA, B. A. PORTER AND M. P. KILGARD. Effects of damage to auditory cortex on the discrimination of speech sounds by rats. PHYSIOL BEHAV 00(0) 000-000, 2010.–The intensity of a noise-induced startle response can be reduced by the presentation of an otherwise neutral stimulus immediately before the noise (“prepulse inhibition” or PPI). We used a form of PPI to study the effects of damage to auditory cortex on the discrimination of speech sounds by rats. Subjects underwent control surgery or treatment of the auditory cortex with the vasoconstrictor endothelin-1. This treatment caused damage concentrated in primary auditory cortex (A1). Both before and after lesions, subjects were tested on 5 tasks, most presenting a pair of human speech sounds (consonant-vowel syllables) so that the capacity for discrimination would be evident in the extent of PPI. Group comparisons failed to reveal any consistent lesion effect. At the same time, the analysis of individual differences in performance by multiple regression suggests that some of the temporal processing required to discriminate speech sounds is concentrated anteroventrally in the right A1. These results also confirm that PPI can be adapted to studies of the brain mechanisms involved in the processing of speech and other complex sounds. Copyright © 2010. Published by Elsevier Inc.

Multifunctional macrophage inhibitory cytokine-1, MIC-1, is a member of the transforming growth factor-beta (TGF-beta) superfamily that plays key roles in the prenatal development and regulation of the cellular responses to stress signals and inflammation and tissue repair after acute injuries in adult life. The stringent control of the MIC-1 expression, secretion, and functions involves complex regulatory mechanisms and the interplay of other growth factor signaling networks that control the cell behavior. The deregulation of MIC-1 expression and signaling pathways has been associated with diverse human diseases and cancer progression. The MIC-1 expression levels substantially increase in cancer cells, serum, and/or cerebrospinal fluid during the progression of diverse human aggressive cancers, such as intracranial brain tumors, melanoma, and lung, gastrointestinal, pancreatic, colorectal, prostate, and breast epithelial cancers. Of clinical interest, an enhanced MIC-1 expression has been positively correlated with poor prognosis and patient survival. Secreted MIC-1 cytokine, like the TGF-beta prototypic member of the superfamily, may provide pleiotropic roles in the early and late stages of carcinogenesis. In particular, MIC-1 may contribute to the proliferation, migration, invasion, metastases, and treatment resistance of cancer cells as well as tumor-induced anorexia and weight loss in the late stages of cancer. Thus, secreted MIC-1 cytokine constitutes a new potential biomarker and therapeutic target of great clinical interest for the development of novel diagnostic and prognostic methods and/or cancer treatment against numerous metastatic, recurrent, and lethal cancers. J. Cell. Physiol. 224: 626-635, 2010. (c) 2010 Wiley-Liss, Inc.

Ablation of functional peroxisomes from all neural cells in Nestin-Pex5 knockout mice caused remarkable neurological abnormalities including motoric and cognitive malfunctioning accompanied by demyelination, axonal degeneration, and gliosis. An oligodendrocyte selective Cnp-Pex5 knockout mouse model shows a similar pathology, but with later onset and slower progression. Until now, the link between these neurological anomalies and the known metabolic alterations, namely the accumulation of very long-chain fatty acids (VLCFA) and reduction of plasmalogens, has not been established. We now focused on the role of peroxisomes in neurons and astrocytes. A neuron-specific peroxisome knockout model, NEX-Pex5, showed neither microscopic nor metabolic abnormalities indicating that the lack of functional peroxisomes within neurons does not cause axonal damage. Axonal integrity and normal behavior was also preserved when peroxisomes were deleted from astrocytes in GFAP-Pex5(-/-) mice. Nevertheless, peroxisomal metabolites were dysregulated in brain including a marked accumulation of VLCFA and a slight reduction in plasmalogens. Interestingly, despite minor targeting of oligodendrocytes in GFAP-Pex5(-/-) mice, these metabolic perturbations were also present in isolated myelin indicating that peroxisomal metabolites are shuttled between different brain cell types. We conclude that absence of peroxisomal metabolism in neurons and astrocytes does not provoke the neurodegenerative phenotype observed after deleting peroxisomes from oligodendrocytes. Lack of peroxisomal metabolism in astrocytes causes increased VLCFA levels in myelin, but this has no major impact on neurological functioning. (c) 2010 Wiley-Liss, Inc.

PURPOSE:: To characterize multiple patterns of vascular changes in leukoaraiosis using in vivo magnetic resonance imaging (MRI) techniques. MATERIALS AND METHODS:: We measured cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and blood-brain-barrier (BBB) leakage in a group of 33 elderly subjects (age: 72.3 +/- 6.8 years, 17 males, 16 females). Leukoaraiosis brain regions were identified in each subject using fluid-attenuated inversion-recovery (FLAIR) MRI. Vascular parameters in the leukoaraiosis regions were compared to those in the normal-appearing white matter (NAWM) regions. Vascular changes in leukoaraiosis were also compared to structural damage as assessed by diffusion tensor imaging. RESULTS:: CBF and CVR in leukoaraiosis regions were found to be 39.7 +/- 5.2% (P < 0.001) and 52.5 +/- 11.6% (P = 0.005), respectively, of those in NAWM. In subjects who did not have significant leukoaraiosis, CBF and CVR in regions with high risk for leukoaraiosis showed a slight reduction compared to the other white matter regions. Significant BBB leakage was also detected (P = 0.003) in leukoaraiosis and the extent of BBB leakage was positively correlated with mean diffusivity. In addition, CVR in NAWM was lower than that in white matter of subjects without significant leukoaraiosis. CONCLUSION:: Leukoaraiosis was characterized by reduced CBF, CVR, and a leakage in the BBB. J. Magn. Reson. Imaging 2010;32:184-190. (c) 2010 Wiley-Liss, Inc.

A brush of 64 microwires was chronically implanted in the ventral premotor cortex of a macaque monkey. Contrary to common approaches, the wires were inserted from the white matter side. This approach, by avoiding mechanical pressure on the dura and pia mater during penetration, disturbed only minimally the cortical recording site. With this approach isolated potentials and multiunit activity were recorded for more than 7 years in about one-third of electrodes. The indirect insertion method also provided an excellent stability within each recording session, and in some cases even allowed recording from the same neurons for several years. Histological examination of the implanted brain region shows only a very marginal damage to the recording area. Advantages and problems related to long-term recording are discussed.

OBJECTIVE: The formation of cerebral aneurysms is associated with endothelial damage and macrophage migration. Hypothesizing that the opening of tight junctions due to the disappearance of the tight junction proteins occludin and zona occludens-1 (ZO-1) in damaged endothelia allows macrophage migration, leading to cerebral aneurysm formation, we investigated the role of tight junction proteins. METHODS: The vascular wall of female rats subjected to hypertension, oophorectomy (OVX), and hemodynamic stress to induce cerebral aneurysms was evaluated morphologically, immunohistochemically, and by quantitative RT-PCR. We also assessed the regulation of tight junction proteins in human brain endothelial cells (HBECs). RESULTS: In the very early stage before aneurysm formation, the expression of occludin and ZO-1 was reduced in injured endothelial cell junctions exhibiting gaps. In the course of aneurysmal progression their reduction progressed and was correlated with macrophage migration. In hypertension along with OVX rats we observed an increase in angiotensin II and the degradation molecules matrix metalloproteinase-9 (MMP-9), nicotinamide-adenine dinucleotide phosphate oxidases and monocyte chemoattractant protein-1. The mineralocorticoid receptor blocker eplerenone increased occludin and ZO-1 expression; this was associated with a reduction in angiotensin II and the degradation molecules and resulted in the inhibition of macrophage exudation and aneurysm formation. In HBECs, occludin and ZO-1 downregulation by angiotensin II and estrogen deficiency was reversed by eplerenone, the MMP inhibitor SB3CT, and apocynin. Our results suggest that macrophage migration is associated with the reduction in tight junction proteins induced by the degradation molecules. CONCLUSION: In rats, the destruction of tight junctions may facilitate macrophage migration and cerebral-aneurysm formation.

PURPOSE: To evaluate the neuroprotective effect of rasagiline (N-propargyl-1 (R)-aminoindan), a selective monoamine oxidase inhibitor, on the survival of retinal ganglion cells (RGCs) in glaucomatous rat eyes. Rasagiline is an FDA approved anti-Parkinson disease drug with neuroprotective capabilities that were shown in many models of brain damage. MATERIALS AND METHODS: The neuroprotective effect of daily intraperitoneal (IP) injections of rasagiline (0.5 mg/kg and 3 mg/kg) was evaluated and compared with saline injections using the translimbal photocoagulation model of experimental glaucoma in Wistar rats. Intraocular pressure (IOP) was measured before and immediately after the laser treatment, and then weekly. Seven weeks after the induction of glaucoma, the animals were killed, the eyes were enucleated and the retinas were prepared as whole mounts. Fluoro-gold had been injected into the superior colliculus 10 days before enucleation, and RGC survival was evaluated by counting the surviving labeled RGCs in a masked way. RESULTS: All rats (n=29) displayed significant IOP elevation and RGC damage. Seven weeks after the induction of glaucoma, the mean RGC survival was 43+/-8% in the rasagiline 3 mg/kg-treated group and 43+/-9% in the rasagiline 0.5 mg/kg-treated group compared with 23%+/-4% in the saline-treated (control) group (P=0.01 and P=0.02, respectively). CONCLUSION: Systemic treatment with rasagiline significantly enhances the survival of RGCs in experimental glaucoma.

Semantic dissociations show that biological stimuli present a further dissociation between animals and plant life. Almost all cases of greater impairment of plant life knowledge were males, suggesting a higher male familiarity with animals possibly derived from different daily activities. To verify this hypothesis, we collected familiarity ratings for normal males and females, for 288 animals, subdivided according to whether they were hunted/fished, or were used as food. The overall familiarity was almost identical between males and females. Males were more familiar with hunted animals, but for them also food animals were more familiar. There was not a consistent effect of hunting/fishing independently of the food/not food classification. The claim that males are generally more proficient with animals knowledge because most hunters/fishers are males seems rather simplistic, and the familiarity structure of the animals category is more complex. An evolution-based account is suggested for the category by sex interaction.