Cerebral Palsy

The phenomenon of intermediate targets is well known in wound ballistics. In forensic science, models are used to reconstruct injury patterns to answer questions regarding the dynamic formation of these unusual injuries. Soft-tissue substitutes or glycerin soap and ordnance gelatin have been well established. Recently, based on previous experiences with artificial bone, a skull-brain model was developed. The goal of this study was to create and analyze a model-supported reconstruction of a real forensic case with a coin as an intermediate target. It was possible not only to demonstrate the “bullet-coin interaction,” but also to recreate the wound pattern found in the victim. This case demonstrates that by using ballistic models, gunshot cases can be reproduced simply and economically, without coming into conflict with ethical guidelines.

ObjectiveThe term benign multiple sclerosis (BMS) is referred to patients who have a mild or absent disability several years after disease clinical onset. Axonal damage can be measured in vivo using proton MR spectroscopy ((1)H-MRS). In this study, we quantified the severity of “global” axonal damage in BMS and early relapsing-remitting (RR) MS patients, using whole brain N-acetylaspartate (WBNAA) (1)H-MRS, to better elucidate the structural correlates of a non-disabling disease evolution.MethodsWBNAA concentration was measured in 37 patients with BMS (mean disease duration 22.3 years) and 17 patients with early RRMS (mean disease duration 4.0 years), using an unlocalized (1)H-MRS sequence. Dual echo and T1-weighted scans were also obtained to measure T2-hyperintense lesion volume (TLV) and normalized brain volume (NBV).ResultsTLV was higher in BMS (mean TLV = 13.1 mL) than in early RRMS patients (mean TLV = 7.2 mL) (P = 0.018), whereas neither NBV (mean NBV: 1491.0 mL in BMS vs 1520.3 mL in RRMS) nor WBNAA concentration (mean WBNAA: 10.5 mmol in BMS vs 11.4 mmol in RRMS) significantly differed between the two groups. In MS patients, no correlation was found between WBNAA concentration and Expanded Disability Status Scale (EDSS), TLV and NBV.ConclusionsThe similar WBNAA concentrations seen in BMS and early RRMS patients fit with the notion that a non-disabling long-term evolution of MS may be due, at least in part, to non-progression of pathology. Such a condition seems to be independent from MRI-visible lesions burden.

Functional neurological changes after surgery combined with data from diffusion tensor imaging (DTI) studies can provide direct evidence of anatomical localization of brain function. The goal of the present study was to characterize mechanisms of spatial neglect using these techniques by analyzing two patients with development or worsening of left neglect after surgery at our hospital in 2008. In both cases, the surgical approach was via the right inferior parietal lobes, and damage to the superior longitudinal fasciculus (SLF) was demonstrated after surgery by DTI tractography. By contrast, neither the inferior longitudinal fasciculus (ILF) nor the inferior fronto-occipital fasciculus (IFOF) was damaged. These results suggest that damage to the right SLF in the inferior parietal lobe plays a critical role in the development of spatial neglect.

In this article, we address the currently accepted dose tolerance parameters for the treatment of high-grade gliomas. The issue of normal tissue tolerance is becoming increasingly important because of the long-term survival of a significant subset of young, good performance status patients and the use of hypofractionated regimens for elderly patients with poor performance status. In addition, we address relevant clinical endpoints including clinical, pathologic, and radiographic changes and highlight the difficulty in discriminating between tumor-related and treatment-related effects. Finally, we review relevant clinical trials addressing issues of dose and/or volume parameters. Future trials for patients with high-grade gliomas should consider the inclusion of a prospective evaluation of neurocognitive function and imaging correlates of the brain to assist in the prediction, prevention, and treatment of radiation-induced damage of normal brain tissue.

The present study was undertaken to reveal the effects of chronic aluminium exposure (10mg/kg/b.wt, intragastrically for 12 weeks) on the oxidative DNA damage and its implication on the expression of p53 and other cell cycle regulatory proteins in male Wister rats. Chronic aluminium exposure resulted in increased formation of 8-hydoxydeoxyguanosine in the mitochondrial DNA isolated from different regions of rat brain. The agarose gel electrophoresis revealed the DNA fragmentation pattern in aluminium-treated rat brain regions. Increased expression of p53 demonstrated that aluminium induces DNA damage. Western blot and mRNA expression analysis demonstrated increased expression of cyclin D1, suggesting disruption of cell cycle. The immunohistochemical studies showed nuclear localization of p53; however, the localization of cyclin D1 was both cytoplasmic and nuclear in aluminium-treated rat brain regions. Thus, the findings of the present study reveal that aluminium induced oxidative damage to DNA may be involved in the neurodegeneration via increase in p53 expression and activation of cell cycle.

Chronic alcohol intake is known to induce the selective neuronal damage associated with increase oxidative-nitrosative stress and activation of inflammatory cascade finally resulting in neuronal apoptosis and thus dementia. In the present study, we investigated the comparative effect of both the isoforms of vitamin E, alpha-tocopherol and tocotrienol against chronic alcohol induced cognitive dysfunction in rats. Male Wistar rats were given ethanol (10g/kg; oral gavage) for ten weeks, and treated with alpha-tocopherol and tocotrienol for the same duration. The learning and memory behavior was assessed using morris water maze and elevated plus maze test. The rats were sacrificed at the end of 10(th) week and cytoplasmic fractions of cerebral cortex and hippocampus were prepared for the quantification of acetylcholinesterase activity, oxidative-nitrosative stress parameters, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). From the 6(th) week onwards, ethanol treated rats showed significant increase in transfer latency in both the behavioural paradigms which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, TNF-alpha and IL-1beta levels in different brain regions of ethanol treated rats. Co-administration of alpha-tocopherol as well as tocotrienol significantly and dose-dependently prevented these behavioral, biochemical and molecular changes in the brains of ethanol treated rats. However, the effects were more pronounced with tocotrienol. The current study thus demonstrates the possible involvement of oxidative-nitrosative stress mediated activation of inflammatory cascade in chronic alcohol-induced cognitive dysfunction and also suggests the effectiveness of vitamin E isoforms, of which tocotrienol being more potent, in preventing the cognitive deficits associated with chronic alcohol consumption.

Recent laboratory evidence implicates matrix metalloproteinases (MMPs) as playing a pivotal role in ischemic and traumatic brain injuries (TBI). Here, quantitative real-time PCR analyses revealed that brains from TBI rats displayed significantly elevated MMP-9 expression at 24 hours post-TBI, which remained upregulated at least until 48 hours after injury. Immunohistochemical analyses similarly revealed significantly increased MMP-9 immunoreactivity at 24 and 48 hours post-TBI. These results demonstrate that alterations in MMPs (i.e., MMP-9) commenced immediately after TBI, suggesting that treatment strategies designed to maintain MMP integrity should be initiated in the acute phase of injury.

While the adverse effects of acrylonitrile (AN) on the central nervous system (CNS) are known to be mediated, at least in part, by the generation of free radicals and oxidative stress, there is a paucity of data on region-specific alterations in biomarkers of oxidative stress in the brain of AN-exposed animals. The present study was designed to examine the effects of AN on biomarkers of oxidative stress in several brain regions of adult Sprague-Dawley rats. Daily intraperitoneal (i.p.) treatment of animals to 0 (control, normal saline solution), 25, 50 or 75mg AN/kg body weight for 7 days resulted in statistically significant (p<0.05) increases in the levels of lipid peroxidation product, malondialdehyde (MDA), in the cortex and cerebellum; a statistically significant (p<0.05) decrease MDA levels were noted in the striatum. Contents of reduced glutathione (GSH) were significantly (p<0.05) decreased in cortex, cerebellum and hippocampus. The activities of the antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were differentially affected by AN and these effects were brain region-specific and AN dose-dependent. Taken together, these data suggest brain region-specific effects of AN on lipid peroxidation, activities of antioxidant enzymes and non-enzymatic antioxidant levels. These effects may provide biochemical evidence for AN-induced neurobehavioral damage and disturbance of monoamine neurotransmitters.

Antifibrotic and organ protective effects of brain natriuretic peptide (BNP) have been reported. In this study, effects of BNP on liver fibrosis were examined in the carbon tetrachloride (CCl(4))-induced liver fibrosis model using BNP-transgenic (Tg) and wild type (WT) mice. Twice-a-week intraperitoneal injections of CCl(4) for 8 weeks resulted in massive liver fibrosis, augmented transforming growth factor (TGF)-beta(1) and type I procollagen alpha(1) chain (Col1a1) mRNA expression, and the hepatic stellate cell (HSC) activation in WT mice, all of which were significantly suppressed in Tg mice. These observations indicate that BNP inhibits liver fibrosis by attenuating the activation of HSCs.

ABSTRACT: BACKGROUND: The human zinc finger protein 191 (ZNF191) is a member of the SCAN domain family of Kruppel-like zinc finger transcription factors. ZNF191 shows 94% identity to its mouse homologue zinc finger protein 191(Zfp191), which is the most highly conserved among the human-mouse SCAN family member orthologues pairs. Zfp191 is widely expressed during early embryogenesis and in adult organs. Moreover, Zfp191-/- embryos have been shown to be severely retarded in development and die approximately at embryonic day E7.5. ZNF191 can specifically interact with the widespread TCAT motif which constitutes the HUMTH01 microsatellite in the tyrosine hydroxylase (TH) gene. Allelic variations of HUMTH01 have been stated to have a quantitative silencing effect on TH gene expression and to correlate with quantitative and qualitative changes in the binding by ZNF191. In addition, ZNF191 displays a suppressive effect on the transcription; however, little downstream targets have identified. RESULTS: We searched for ZNF191 target genes by using a transient overexpression and knockdown strategy in the human embryo kidney (HEK293) cells. Microarray analyses identified 6094 genes modulated by overexpression of ZNF191 and 3332 genes regulated by knockdown of ZNF191, using a threshold of 1.2-fold. Several interested candidate genes, validated by real time RT-PCR, were correlated well with the array data. Interestingly, 1456 genes were identified in both transient overexpression and transient knockdown strategies. The GeneMapp and MappFinder software packages were further used for pathway analysis of these significantly altered genes. Several gene pathways were found to be involved in processes of the regulation of kinase activity, transcription, angiogenesis, brain development and response to DNA damage. CONCLUSION: Our analysis reveals for the first time that ZNF191 is a pleiotropic factor that has a role in hematopoiesis, brain development and cancers.