Cerebral Palsy

Increasing awareness and understanding of the implications of concussion have shaped a more proactive management approach to this problem. Although the incidence of brain injuries in adolescent athletes is probably in the range of 1.6 to 3.8 million per year (Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Facts for physicians about mild traumatic brain injury. Available at: www.cdc.gov/ncipc/pubres/tbi_toolkit/physicians/mtbi/mtbi.pdf), difficulties in recognizing and diagnosing this condition mean that as many as 80% go unrecognized and have led to its being known as “the silent epidemic.” Attempts to improve the evaluation on the sidelines, in the outpatient clinic, and in the home are helping to improve management. Better understanding of the prognosis and clinical course of concussion, as well as the importance of physical and mental rest, have also helped healthcare providers to make better decisions about allowing athletes to return to play.

To study the content of protein S-100 and tumor-necrosis factor-alpha (TNF-alpha ) in the serum of patients with discirculatory encephalopathy (DE), stages I and II, 108 patients have been examined. The diagnosis of vascular damage of the brain has been confirmed by ultrasound and MRI-examination. Patients with DE, stage II, had significantly higher levels of protein S-100 and TNF-alpha (0,764+/-0,021 optical density units (ODU) and 0,797+/-0,039 pg/l, respectively) compared to the control group (0,540+/-0,015 ODU and 0,528+/-0,001 pg/l; p<0,001). Lesser differences were found between patients with stage II and stage I. The levels of protein S-100 and TNF-alpha increased with age and illness duration (p<0,05). The data obtained can be used in diagnostics of chronic cerebral blood circulation disorders and prognosis of disease outcome.

A prospective examination of 103 newborns with hypoxic damage of the central nervous system of moderate severity was conducted on the 4-7, 10-14 and 21-28 days after birth and included clinical examination, neurosonographic study with dopplerography of great brain arteries and biochemical study of venous blood and urine. Children with ventriculomegalia were treated with diacarb. A control group included 15 newborns without signs of survived hypoxia. Ventriculomegalia was found in 29% of children in the main group and remained till the end of neonatal period in 15%, with moderate and large dilatation in 63,5% and mild dilatation of anterior horns of lateral ventriculars in 36,5%. The markers of development and long remaining ventriculomegalia are specified as follows: the morphofunctional immaturity of the brain (RR=1,7; 95%CI 1,16-2,45), absence of compensatory reduction of resistance index (RI) in anterior brain arteries on 4-7 days of life (RR=3,03; 95%CI 2,11-4,31), metabolic acidosis – the bicarbonate level in the venous blood less than 21 mmol/l (RR=2,9; 95% CI 1,66-5,02), carbanhydrase activation – bicarbonate concentration in the urine less than 5 mmol/mcmol of creatinine on 4-7 days of life (RR=3,81; 95%CI 2,87-5,02). Diacarb in ventriculomegalia should be prescribed only in case of disturbance of the organism compensatory reaction because it causes the significant increase of compensatory reduced RI. The drug has a nephrotoxic effect and causes metabolic acidosis.

Glutamate excitotoxicity is involved in many neurodegenerative diseases including Alzheimer’s disease (AD). Attenuation of glutamate toxicity is one of the therapeutic strategies for AD. Wolfberry (Lycium barbarum) is a common ingredient in oriental cuisines. A number of studies suggest that wolfberry has anti-aging properties. In recent years, there is a trend of using dried Wolfberry as food supplement and health product in UK and North America. Previously, we have demonstrated that a fraction of polysaccharide from Wolfberry (LBA) provided remarkable neuroprotective effects against beta-amyloid peptide-induced cytotoxicity in primary cultures of rat cortical neurons. To investigate whether LBA can protect neurons from other pathological factors such as glutamate found in Alzheimer brain, we examined whether it can prevent neurotoxicity elicited by glutamate in primary cultured neurons. The glutamate-induced cell death as detected by lactate dehydrogenase assay and caspase-3-like activity assay was significantly reduced by LBA at concentrations ranging from 10 to 500 mug/ml. Protective effects of LBA were comparable to memantine, a non-competitive NMDA receptor antagonist. LBA provided neuroprotection even 1 h after exposure to glutamate. In addition to glutamate, LBA attenuated N-methyl-D: -aspartate (NMDA)-induced neuronal damage. To further explore whether LBA might function as antioxidant, we used hydrogen peroxide (H(2)O(2)) as oxidative stress inducer in this study. LBA could not attenuate the toxicity of H(2)O(2). Furthermore, LBA did not attenuate glutamate-induced oxidation by using NBT assay. Western blot analysis indicated that glutamate-induced phosphorylation of c-jun N-terminal kinase (JNK) was reduced by treatment with LBA. Taken together, LBA exerted significant neuroprotective effects on cultured cortical neurons exposed to glutamate.

A West Highland White Terrier was brought to our veterinary hospital with the chief complaints of seizures and staggering gait. When cephalic Magnetic resonance imaging (MRI) was performed, a symmetrical lesion was found in the basal ganglion. Suspecting a metabolic disorder, an abdominal ultrasonography was performed, and a tumor was found in the pancreas. The pancreatic tumor was surgically removed based on suspicion that it had induced the brain damage. The resected tumor was histopathologically diagnosed as an insulinoma. After removal, recurrence of neurological symptoms was not observed. MRI 3 months post-operation showed a reduction in the size of the brain lesion. Consequently, the tumor was thought to have induced the lesion in the basal ganglion, and this was verified by MRI. This case was considered to be extremely rare.

Erythropoietin receptor (EpoR) binding mediates neuroprotection by endogenous Epo or by exogenous recombinant human (rh)Epo. The level of EpoR gene expression may determine tissue responsiveness to Epo. Thus, harnessing the neuroprotective power of Epo requires an understanding of the Epo-EpoR system and its regulation. We tested the hypothesis that neuronal expression of EpoR is required to achieve optimal neuroprotection by Epo. The ventral limbic region (VLR) in the rat brain was used because we determined that its neurons express minimal EpoR under basal conditions, and they are highly sensitive to excitotoxic damage, such as occurs with pilocarpine-induced status epilepticus (Pilo-SE). We report that (i) EpoR expression is significantly elevated in nearly all VLR neurons when rats are subjected to 3 moderate hypoxic exposures, with each separated by a 4-day interval; (ii) synergistic induction of EpoR expression is achieved in the dorsal hippocampus and neocortex by the combination of hypoxia and exposure to an enriched environment, with minimal increased expression by either treatment alone; and (iii) rhEpo administered after Pilo-SE cannot rescue neurons in the VLR, unless neuronal induction of EpoR is elicited by hypoxia before Pilo-SE. This study thus demonstrates using environmental manipulations in normal rodents, the strict requirement for induction of EpoR expression in brain neurons to achieve optimal neuroprotection. Our results indicate that regulation of EpoR gene expression may facilitate the neuroprotective potential of rhEpo.

Anti-aquaporin-4 antibody (NMO-IgG) is used as a diagnostic marker for neuromyelitis optica (NMO). Although the mechanism of spinal cord lesions in NMO has been investigated, that of extensive hemispheric lesions with brain edema remains unclear. Here we report a 36-year-old woman with NMO positive for NMO-IgG, who developed an acute disseminating encephalomyelitis (ADEM)-like episode after Mycoplasma pneumoniae infection. Brain MRI T2-weighted images demonstrated asymmetric tumefactive hyperintense lesions in the subcortical white matter. Importantly, no lesions on T1-weighted images were enhanced after intravenous gadolinium administration on serial brain MRIs, suggesting preserved integrity of the blood-brain barrier (BBB). Likewise, the corresponding apparent diffusion coefficient maps demonstrated persistent hyperintensity changes, which represented vasogenic edema associated with glial damage and consequent neuronal loss. The findings suggest possible involvement of deficient water elimination associated with seropositivity to NMO-IgG in the induction of vasogenic edema even in the presence of intact and functional BBB.

BACKGROUND: Binge drinking may lead to brain damage. The aim of the present study was to compare the cognitive abilities of binge and non-binge drinkers in tasks which test functions linked to discrete areas of the prefrontal cortex. METHODS: Non-binge and binge drinkers were identified according to their binge score derived from the Alcohol Use Questionnaire. Cognitive performance was tested with the Spatial Working Memory task (SWM) linked to the dorsolateral prefrontal cortex, Intra/Extra dimensional shift & reversal task (IED) linked to dorsolateral prefrontal cortex (shift) and to orbitofrontal cortex (reversal), Paired Associates Learning task (PAL) linked to temporal cortex, and Reaction Time Task (RTI) a task measuring motor impulsivity (Inferior frontal gyrus). Personality traits, alcohol outcome expectancies and mood were also evaluated. RESULTS: Binge drinkers recorded a significantly shorter movement time to target in the RTI, and completed fewer stages on first trial in the PAL, compared with non-bingers. In the IED as well as in the SWM, only female binge drinkers were more impaired than non-binge drinkers. CONCLUSIONS: Functions linked to dorsolateral prefrontal cortex may be more impaired in female, whereas functions linked with the temporal lobe may be impaired in both male and female binge drinkers compared to non-binge drinkers. Functions linked to orbitofrontal cortex were not impaired. The increased speed of response in the RTI in binge drinkers may indicate an increased motor impulsivity in binge drinkers.

The aggregation of amyloid beta-peptide (Abeta) in plaques in brain tissue is highly associated with Alzheimer’s disease (AD). Aberrant homeostasis of cerebral metals such as Zn(2+) and Cu(2+) may facilitate the formation of the pathogenetic amyloid plaques. Further, the accumulation of redox-active Cu(2+) in these plaques leads to the generation of reactive oxygen species, which mediates the conspicuous oxidative damage to the brain in AD. In this study, the effect of macrocyclic polyamine chelators, cyclen and cyclam, on the aggregation of Abeta40 induced by Zn(2+) or Cu(2+) was investigated using turbidometry, thioflavin T fluorescence spectroscopy, electrospray ionization mass spectrometry, inductively coupled plasma mass spectrometry, BCA protein assay, circular dichroism spectroscopy, and atomic force microscopy. The solubility of Zn(2+)- or Cu(2+)-induced Abeta40 aggregates is greatly increased by cyclen or cyclam as compared to that without chelators, and the solubilization is not affected by other essential metal ions such as Ca(2+) and Mg(2+). Moreover, the metal-induced beta-sheet structure of Abeta40 can be reconverted to its original random coil conformation, and the generation of H(2)O(2) mediated by the Cu-Abeta40 complex can also be inhibited by these chelators. Preliminary tests on neuronal cells indicate that these chelators are capable of reducing the toxicity of metal-Abeta40 aggregates. These observations suggest that cyclen and cyclam could be lead compounds as neuroprotective or neurorescue agents for the treatment of AD.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Studies of human TBI demonstrate that the cerebellum is sometimes affected even when the initial mechanical insult is directed to the cerebral cortex. Some of the components of TBI, including ataxia, postural instability, tremor, impairments in balance and fine motor skills, and even cognitive deficits, may be attributed in part to cerebellar damage. Animal models of TBI have begun to explore the vulnerability of the cerebellum. In this paper, we review the clinical presentation, pathogenesis, and putative mechanisms underlying cerebellar damage with an emphasis on experimental models that have been used to further elucidate this poorly understood but important aspect of TBI. Animal models of indirect (supratentorial) trauma to the cerebellum, including fluid percussion, controlled cortical impact, weight drop impact acceleration, and rotational acceleration injuries, are considered. In addition, we describe models that produce direct trauma to the cerebellum as well as those that reproduce specific components of TBI including axotomy, stab injury, in vitro stretch injury, and excitotoxicity. Overall, these models reveal robust characteristics of cerebellar damage including regionally specific Purkinje cell injury or loss, activation of glia in a distinct spatial pattern, and traumatic axonal injury. Further research is needed to better understand the mechanisms underlying the pathogenesis of cerebellar trauma, and the experimental models discussed here offer an important first step toward achieving that objective.