Cerebral Palsy » Brain Damage

Task-specific contribution of the human striatum to perceptual-motor skill learning.

admin — Thu, 08 Jul 2010 14:25:47 +0000

Acquisition of new perceptual-motor skills depends on multiple brain areas, including the striatum. However, the specific contribution of each structure to this type of learning is still poorly understood. Focusing on the striatum, we proposed (a) to replicate the finding of impaired rotary pursuit (RP) and preserved mirror tracing (MT) in Huntington’s disease (HD); and (b) to further explore this putative learning dissociation with other human models of striatal dysfunction (i.e., Parkinson’s disease and focal vascular damage) and two new paradigms (i.e., Geometric Figures, GF, and Control Stick, CS) of skill learning. Regardless of the etiology, participants with damage to the striatum showed impaired learning of visuomotor tracking skills (i.e., RP and GF), whereas the ability to learn skills that require motor adaptation (i.e., MT and CS) was not affected. These results suggest a task-specific involvement of the striatum in the early stages of skill learning.

Effect of treadmill exercise on Purkinje cell loss and astrocytic reaction in the cerebellum after traumatic brain injury.

admin — Thu, 08 Jul 2010 14:25:46 +0000

The cerebellum is one of the brain areas, which is selectively vulnerable to forebrain traumatic brain injuries (TBI). Physical exercise in animals is known to promote cell survival and functional recovery after brain injuries. However, the detailed pathologic and functional alterations by exercise following an indirect cerebellar injury induced by a TBI are largely unknown. We determined the effects of treadmill exercise on survival of Purkinje neurons and on a population of reactive astrocytes in the gyrus of lobules VIII and IX of the cerebellum after TBI. The rats were divided into four groups: the sham-operation group, the sham-operation with exercise group, the TBI-induction group, and the TBI-induction with exercise group. Cell biological changes of Purkinje neurons following indirect cerebellar injury were analyzed by immunohistochemistry. TBI induced loss of calbindin-stained Purkinje neurons in the posterior region of the cerebellum and TBI also increased formation of reactive astroyctes in both the granular and molecular layers of the cerebellar posterior region. Treadmill exercise for 10 days after TBI increased the number of calbindin-stained Purkinje neurons and suppressed formation of reactive astroyctes. The present study provides the possibility that treadmill exercise may be an important mediator to enhance survival of Purkinje neurons in TBI-induced indirect cerebellar injury. Copyright © 2010. Published by Elsevier Ireland Ltd.

Multi-parametric neuroimaging evaluation of cerebrotendinous xanthomatosis and its correlation with neuropsychological presentations.

admin — Thu, 08 Jul 2010 14:25:43 +0000

ABSTRACT: BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder. Recent studies show that brain damage in CTX patients extends beyond the abnormalities observed on conventional magnetic resonance imaging (MRI). We studied the MRI and 99mTc -ethyl cysteinate dimer single photon emission computed tomography (SPECT) findings of CTX patients and made a correlation with the neuropsychological presentations. METHODS: Diffusion tensor imaging (DTI) and 3D T1-weighted images of five CTX patients were compared with 15 age-matched controls. Voxel-based morphometry (VBM) was use to delineate gray matter (GM) and white matter (WM) volume loss. Fractional anisotropy (FA), mean diffusivity (MD), and eigenvalues derived from DTI were used to detect WM changes and correlate with neuropsychological results. SPECT functional studies were used to correlate with GM changes. RESULTS: Cognitive results showed that aside from moderate mental retardation, the patient group performed worse in all cognitive domains. Despite the extensive GM atrophy pattern, the cerebellum, peri-Sylvian regions and parietal-occipital regions were correlated with SPECT results. WM atrophy located in the peri-dentate and left cerebral peduncle areas corresponded with changes in diffusion measures, while axial and radial diffusivity suggested both demyelinating and axonal changes. Changes in FA and MD were preceded by VBM in the corpus callosum and corona radiata. Cognitive results correlated with FA changes. CONCLUSION: In CTX, GM atrophy affected the perfusion patterns. Changes in WM included atrophy, and axonal changes with demyelination. Disconnection of major fiber tracts among different cortical regions may contribute to cognitive impairment.

Differentiation between brain tumor recurrence and radiation injury using perfusion, diffusion-weighted imaging and MR spectroscopy.

admin — Thu, 08 Jul 2010 14:25:41 +0000

BACKGROUND: Differentiation between tumor recurrence/vital tumor tissue and radionecrosis based on conventional diagnostic imaging is impossible because of the likeness of the images. In such circumstances advanced MRI techniques (PWI, DWI, 1HMRS) seem to be helpful. The aim of our study was to evaluate the diagnostic effectiveness of PWI, DWI and 1HMRS in the differentiation of the tumor recurrence from radiation related injury. MATERIAL AND METHODS: The retrospective analysis comprised 11 contrast-enhancing lesions observed in 8 patients treated for gliomas with radiotherapy or radiochemotherapy. 5 out of 11 contrast-enhancing lesions were tumor recurrences whereas 6 out of 11 radiation-related injuries. The MR examinations comprised of conventional MR imaging (T1-SE, T1-MPRAGE with CE, T2-TSE, T2 FLAIR) and PWI, DWI, 1HMRS. Mean and maximum rCBV values of each contrast-enhancing lesion were calculated. These values were normalized to normal appearing white matter. Mean normalized ADC ratio to normal appearing white matter and mean ADC obtained from contrast-enhancing lesions were analysed. In 1HMRS only those voxels which were placed in solid part of the contrast-enhancing lesion were analysed and Cho/Cr, Cho/NAA ratios presented. RESULTS: Mean normalized rCBVmax (2.44 +/- 0.73 for tumor recurrence vs. 0.78 +/- 0.46 for radiation injury; p < 0.001) and mean normalized rCBVmean (1.46 +/- 0.49 for tumor recurrence vs. 0.49 +/- 0.38 for radiation injury; p < 0.005) were significantly higher in the recurrent gliomas group than in the radiation injury one. It was observed that normalized rCBVmax higher than 1.7 and normalized rCBVmean higher than 1.25 is highly indicative for recurrent glioma whereas normalized rCBVmax lower than 1.0 and normalized rCBVmean lower than 0.5 is highly indicative for radiation injury. Results obtained in DWI and 1HMRS were not statistically significant different between two analysed groups. Mean ADCce: 1.06 +/- 0.18 x 10-3 mm2/s for tumor recurrence vs. 1.13 +/- 0.13 x 10-3 mm2/s for radiation injury; p = 0.51. Mean normalized ADC: 1.55 +/- 0.39 x 10-3 mm2/s for tumor recurrence vs. 1.55 +/- 0.18 x 10-3 mm2/s for radiation injury; p = 0.98. Median Cho/Cr ratio: (2.16min/max [1.67-3.15] for tumor recurrence vs. 1.34min/max [1.13-2.37] for radiation injury; p = 0.15), median Cho/NAA ratio (1.9min/max [0.86-2.36] for tumor recurrence vs. 2.11min/max [0.97 vs. 2.87] for radiation injury; p = 0.51). CONCLUSIONS: Among the analyzed advanced neuroimaging methods PWI seems to be most reliable in differentiation between tumor regrowth/recurrence and radiation necrosis. In these results mean rCBV is a better differing factor than max rCBV. Proton MR spectroscopy (1HMRS) and DWI do not differentiate analyzed groups with statistical significance, despite tendency to lower ADC values in recurrence group than in radiation injury one.

Genetic regulation of microglia activation, complement expression, and neurodegeneration in a rat model of traumatic brain injury.

admin — Thu, 08 Jul 2010 14:25:39 +0000

Secondary brain damage following traumatic brain injury in part depends on neuroinflammation, a process where genetic factors may play an important role. We examined the response to a standardized cortical contusion in two different inbred rat strains, Dark Agouti (DA) and Piebald Virol Glaxo (PVG). Both are well characterized in models of autoimmune neuroinflammation, where DA is susceptible and PVG resistant. We found that infiltration of polymorphonuclear granulocytes (PMN) at 3-day postinjury was more pronounced in PVG. DA was more infiltrated by T cells at 3-day postinjury, showed an enhanced glial activation at 7-day postinjury and higher expression of C3 complement at 7-day postinjury. Neurodegeneration, assessed by Fluoro-Jade, was also more pronounced in the DA strain at 30-day postinjury. These results demonstrate differences in the response to cortical contusion injury attributable to genetic influences and suggest a link between injury-induced inflammation and neurodegeneration. Genetic factors that regulate inflammation elicited by brain trauma may be important for the development of secondary brain damage.

Inhibitory action of antioxidants (ascorbic acid or alpha-tocopherol) on seizures and brain damage induced by pilocarpine in rats.

admin — Thu, 08 Jul 2010 14:25:38 +0000

Temporal lobe epilepsy is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. The objectives of this work were to comparatively study the inhibitory action of antioxidants (ascorbic acid or alpha-tocopherol) on behavioral changes and brain damage induced by high doses of pilocarpine, aiming to further clarify the mechanism of action of these antioxidant compounds. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (250 or 500 mg/kg, i.p.) and alpha-tocopherol (200 or 400 mg/kg, i.p.) on the behavior and brain lesions observed after seizures induced by pilocarpine (400 mg/kg, i.p., P400 model) in rats. Ascorbic acid or alpha-tocopherol injections prior to pilocarpine suppressed behavioral seizure episodes. These findings suggested that free radicals can be produced during brain damage induced by seizures. In the P400 model, ascorbic acid and alpha-tocopherol significantly decreased cerebral damage percentage. Antioxidant compounds can exert neuroprotective effects associated with inhibition of free radical production. These results highlighted the promising therapeutic potential of ascorbic acid and alpha-tocopherol in treatments for neurodegenerative diseases.

Oxidized purine nucleotides, genome instability and neurodegeneration.

admin — Thu, 08 Jul 2010 14:25:36 +0000

Oxidative DNA damage can be the consequence of endogenous metabolic processes and exogenous insults and several DNA repair enzymes provide protection against the toxic effects of oxidized DNA bases. Here we review the increasing knowledge on the relationship between an oxidized dNTPs pool and genome instability. The review also describes some important progress toward understanding the role of oxidative DNA damage and its repair in neurodegenerative diseases. In particular the hMTH1 hydrolase destroys oxidized nucleic acid precursors to prevent their harmful incorporation into DNA and RNA. Based on results obtained in our transgenic mouse overexpressing hMTH1 in the brain we discussed the mechanisms by which this hydrolase protects against neurodegeneration in Huntington disease models. Copyright © 2010. Published by Elsevier B.V.

Angiotensin-converting enzyme (ACE) inhibitors exacerbate histological damage and motor deficits after experimental traumatic brain injury.

admin — Thu, 08 Jul 2010 14:25:33 +0000

Angiotensin-converting enzyme (ACE) inhibitors are widely used as blood pressure medications in hypertensive individuals. However, ACE inhibitors also play an integral role in the breakdown of neuronal substance P, which has been recently implicated in the development of functional deficits following traumatic brain injury (TBI). The present study therefore examined the effects of ACE inhibitors on histological and motor outcome following TBI. Male Sprague-Dawley rats were treated with Captopril, Enalapril or equal volume saline for 7 days prior to the induction of diffuse TBI using the impact acceleration model. At 5h post-injury, animals administered Captopril demonstrated significantly increased substance P immunoreactivity compared to vehicle controls (p<0.01), and increased dark cell change that persisted to 7 days post-trauma. Captopril also resulted in exacerbated motor deficits compared to vehicle treated animals (p<0.05) as assessed by the rotarod test over a 7-day post-traumatic period. Administration of the alternative ACE inhibitor, Enalapril, likewise exacerbated motor deficits, confirming a class effect of ACE inhibitors rather than a compound effect specific to Captopril. We conclude that ACE inhibitors are deleterious to outcome following TBI, presumably by impairing the degradation of substance P and increasing substance P mediated neuronal injury. Copyright © 2010. Published by Elsevier Ireland Ltd.

Cytokines mediated inflammation and decreased neurogenesis in animal models of depression.

admin — Thu, 08 Jul 2010 14:25:30 +0000

In patients with major depression or in animal models of depression, significantly increases in the concentrations of pro-inflammatory cytokines have been consistently reported. Proinflammatory cytokines can stimulate the hypothalamic-pituitary-adrenal (HPA) axis to release stress hormone, glucocorticoids. As a consequence of excessive inflammatory response triggered by pro-inflammatory cytokines in the periphery, free radicals, oxidants and glucocorticoids are over-produced, which can affect glial cell functions and damage neurons in the brain. Indeed, decreased neurogenesis and the dysfunction of neurotrophic system (up- or down-regulations of neurotrophins and their receptors) have been recently found. Effective treatments for depressive symptoms, such as antidepressants and omega-3 fatty acids can increase or modulate neurotrophic system and enhance neurogenesis. However, the relationship between glial cells; microglia (mostly involved in neuroinflammation) and astrocytes (producing neurotrophins), and the contribution of inflammation to decreased neurogenesis and dysfunction of neurotrophic system are almost unknown. This review first introduces changes in behavior, neurotransmitter, cytokine and neurogenesis aspects in depressed patients and several animal models of depression, secondly explores the possible relationship between pro- and anti-inflammatory cytokines and neurogenesis in these models, then discusses the effects of current treatments on inflammation, neurotrophic system and neurogenesis, and finally pointes out the limitations and future research directions. Copyright © 2010. Published by Elsevier Inc.

Soman Increases Neuronal COX-2 Levels: Possible Link between Seizures and Protracted Neuronal Damage.

admin — Thu, 08 Jul 2010 14:25:23 +0000

Nerve agent-induced seizures cause neuronal damage in brain limbic and cortical circuits leading to persistent behavioral and cognitive deficits. Without aggressive anticholinergic and benzodiazepine therapy, seizures can be prolonged and neuronal damage progresses for extended periods of time. The objective of this study was to determine the effects of the nerve agent soman on expression of cyclooxygenase-2 (COX-2), the initial enzyme in the biosynthetic pathway of the proinflammatory prostaglandins and a factor that has been implicated in seizure initiation and propagation. Rats were exposed to a toxic dose of soman and scored behaviorally for seizure intensity. Expression of COX-2 was determined throughout brain from 4 hr to 7 days after exposure by immunohistochemistry and immunoblotting. Microglial activation and astrogliosis were assessed microscopically over the same time-course. Soman increased COX-2 expression in brain regions known to be damaged by nerve agents (e.g., hippocampus, amygdala, piriform cortex and thalamus). COX-2 expression was induced in neurons, and not in microglia or astrocytes, and remained elevated through 7 days. The magnitude of COX-2 induction was correlated with seizure intensity. COX-1 expression was not changed by soman. Increased expression of neuronal COX-2 by soman is a late-developing response relative to other signs of acute physiological distress caused by nerve agents. COX-2-mediated production of prostaglandins is a consequence of the seizure-induced neuronal damage, even after survival of the initial cholinergic crisis is assured. COX-2 inhibitors should be considered as adjunct therapy in nerve agent poisoning to minimize nerve agent-induced seizure activity. Copyright © 2010. Published by Elsevier B.V.