Isokinetic analysis of the elbow joint in children with cerebral palsy

The joint torque is an important variable related to children with cerebral palsy. The present study analyzed kinetic parameters during elbow flexion and extension movements in healthy and cerebral palsy children. Ten healthy and 10 cerebral palsy children participated of the study. An isokinetic dynamometer was used to measure the elbow mean peak torque, mean angle peak torque, coefficient of variation and acceleration during flexion and extension movements at different angular speeds. The mean peak torque on extension movement in healthy children group was significant higher compared to the cerebral palsy group. The coefficient of variation on both flexion and extension movements was significantly higher in cerebral palsy group. However there were significantly difference on both groups compared the lowest and highest velocities. Although the results showed no difference in flexor peak torque, the acceleration is significantly lower in lowest and highest angular velocity.

Outcomes of correction of internal hip rotation in patients with spastic cerebral palsy using proximal femoral osteotomy

Internal hip rotation (IHR) is the major cause of intoeing gait in patients with cerebral palsy (CP). Femoral derotation osteotomy (FDO) is the preferred treatment to correct excessive anteversion, however the condition may persist or recur postoperatively. Retrospective clinical and kinematic evaluation of 75 spastic diplegic CP patients was conducted for a mean duration of 22 months following proximal FDO. The patients were divided into two groups depending on the correction or persistence of IHR evident at kinematics after surgery. If corrected, mean patient follow-up was extended to 53 months. Outcomes were analyzed using Two Proportions Equality, Mann-Whitney and Wilcoxon tests. IHR persisted in 33.3% of cases at mean follow-up of 22 months and subtrochanteric femur osteotomy was more frequent in this group (p = 0.033). Thirty-five of the fifty-four patients with first-round gait correction were monitored during the extended follow-up. Those for whom IHR recurred (9.5%) had undergone FDO at a comparatively younger age. Patient gender, operations prior to or at the time of femoral osteotomy, topographic classification, GMFCS level, or the extent of preoperative clinical and kinematic abnormalities had no apparent influence on persistence or recurrence of abnormal gait. (C) 2012 Elsevier B.V. All rights reserved.

Study of cerebral gene expression densities using Voronoi analysis

As the available public cerebral gene expression image data increasingly grows, the demand for automated methods to analyze such large amount of data also increases. An important study that can be carried out on these data is related to the spatial relationship between gene expressions. Similar spatial density distribution of expression between genes may indicate they are functionally correlated, thus the identification of these similarities is useful in suggesting directions of investigation to discover gene interactions and their correlated functions. In this paper, we describe the use of a high-throughput methodology based on Voronoi diagrams to automatically analyze and search for possible local spatial density relationships between gene expression images. We tested this method using mouse brain section images from the Allen Mouse Brain Atlas public database. This methodology provided measurements able to characterize the similarity of the density distribution between gene expressions and allowed the visualization of the results through networks and Principal Component Analysis (PCA). These visualizations are useful to analyze the similarity level between gene expression patterns, as well as to compare connection patterns between region networks. Some genes were found to have the same type of function and to be near each other in the PCA visualizations. These results suggest cerebral density correlations between gene expressions that could be further explored. (C) 2011 Elsevier B.V. All rights reserved.

Pre, intra and post-ischemic hypothermic neuroprotection in temporary focal cerebral ischemia in rats: morphometric analysis

Objective: To evaluate the neuroprotection of mild hypothermia, applied in different moments, in temporary focal cerebral ischemia in rats. Methods: Rats was divided into Control (C), Sham (S), Ischemic-control(IC), Pre-ischemic Hypothermia (IH1), Intra-ischemic Hypothermia (IH2), and Post-ischemic Hypothermia (IH3) groups. Morphometry was performed using the KS400 software (Carl Zeiss (R)) in coronal sections stained by Luxol Fast Blue. Ischemic areas and volumes were obtained. Results: Statistically, blue areas showed difference for C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.01; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH vs. IH2 (p=0.39; p=0.85; p=0.63). Red areas showed difference between C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.009; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH1 vs. IH2 (p=0.48; p=0.27; p=0.68). Average ischemic areas and ischemic volumes showed difference between IC vs. IH1 and IC vs. IH2 (p=0.0001 and p=0.0011), and no difference between IC vs. IH3 and IH1 vs. IH2 (p=0.57; p=0.79). Conclusion: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.

Analysis of the NMDA in Focal Cerebral Ischemia in Rats

NMDAR (N-methyl-D-aspartate receptor) is one subtype of ionotrophic glutamate receptor which is extensively distributed in the central nervous system (CNS). In the mammalian CNS, NMDAR serves prominent roles in the pathophysiologic process of cerebral ischemia. This study aimed to investigate the pattern of expression of protein and gene of the excitatory neurotransmitter NMDAR in experimental focal cerebral ischemia and the hole of neuroprotection with hypothermia and ketoprofen. 120 rats were randomly divided into 6 groups (20 animals each): control - no surgery; sham - simulation of surgery; ischemic - focal ischemia for 1 hour, without reperfusion; ischemic + intraischemic hypothermia; ischemic + previous intravenous ketoprofen, and ischemic + hypothermia and ketoprofen. Ten animals from each experimental group were used to establish the volume of infarct. Transient focal cerebral ischemia was obtained in rats by occlusion of the middle cerebral artery with an intraluminal suture. The infarct volume was measured using morphometric analysis of infarct areas defined by triphenyl tetrazolium chloride and the patterns of expression of the protein and gene NMDA were evaluated by immunohistochemistry and quantitative real-time PCR, respectively. Increases in the protein and gene NMDA receptor in the ischemics areas were observed and these increases were reduced by hypothermia and ketoprofen. The increase in the NMDA receptor protein and gene expression observed in the ischemic animals was reduced by neuroprotection (hypothermia and ketoprofen). The NMDA receptor increases in the ischemic area suggests that the NMDA mediated neuroexcitotoxicity plays an important role in cell death and that the neuroprotective effect of both, hypothermia and ketoprofen is directly involved with the NMDA.

Quantitative comparison of mobility and gross motor function in Brazilian children with cerebral palsy

Background: Cerebral palsy (CP) presents changes in posture and movement as a core characteristic, which requires therapeutic monitoring during the habilitation or rehabilitation of children. Besides clinical treatment, it is fundamental that professionals use systems of evaluation to quantify the difficulties presented to the individual and assist in the organization of a therapeutic program. The aim of this study was to quantitatively verify the performance of children with spastic di-paresia type CP. Methods: The Pediatric Evaluation of Disability Inventory (PEDI) and Gross Motor Function Classification System (GMFM) tests were used and classification made through the GMFCS in the assessment of 7 patients with CP, 4 females and 3 males, average age of 9 years old. Results: According to GMFCS scales, 17% (n=1) were level II and 83% (n=6) were level III. The PEDI test and 88 GMFM items were used in the area of mobility. We observed that there was high correlation between mobility and gross motor function with Pearson's correlation coefficient =0.929) showing the likely impact of these areas in the functional skills and the quality of life of these patients. Conclusion: We suggest the impact of the limitation of the areas in functional skills and quality of life of these patients.

Phenylephrine-induced hypertension during transient middle cerebral artery occlusion alleviates ischemic brain injury in spontaneously hypertensive rats

Arterial hypertension is a major risk factor for ischemic stroke. However, the management of preexisting hypertension is still controversial in the treatment of acute stroke in hypertensive patients. The present study evaluates the influence of preserving hypertension during focal cerebral ischemia on stroke outcome in a rat model of chronic hypertension, the spontaneously hypertensive rats (SHR). Focal cerebral ischemia was induced by transient (1 h) occlusion of the middle cerebral artery, during which mean arterial blood pressure was maintained at normotension (110-120 mm Hg, group 1, n=6) or hypertension (160-170 mm Hg, group 2, n=6) using phenylephrine. T2-, diffusion- and perfusion-weighted MRI were performed serially at five different time points: before and during ischemia, and at 1, 4 and 7 days after ischemia. Lesion volume and brain edema were estimated from apparent diffusion coefficient maps and T2-weighted images. Regional cerebral blood flow (rCBF) was measured within and outside the perfusion deficient lesion and in the corresponding regions of the contralesional hemisphere. Neurological deficits were evaluated after reperfusion. Infarct volume, edema, and neurological deficits were significantly reduced in group 2 vs. group 1. In addition, higher values and rapid restoration of rCBF were observed in group 2, while rCBF in both hemispheres was significantly decreased in group 1. Maintaining preexisting hypertension alleviates ischemic brain injury in SHR by increasing collateral circulation to the ischemic region and allowing rapid restoration of rCBF. The data suggest that maintaining preexisting hypertension is a valuable approach to managing hypertensive patients suffering from acute ischemic stroke. Published by Elsevier B.V.

Cerebral amyloid angiopathy impact on endothelium

Cerebral amyloid angiopathy (CAA) is an age-associated disease characterized by amyloid deposition in cerebral and meningeal vessel walls. CAA is detected in the majority of the individuals with dementia and also in a large number of non-demented elderly individuals. In addition, CAA is strongly associated with Alzheimer's disease (AD) pathology. Mechanical consequences including intra-cerebral or subarachnoid hemorrhage remains CAA most feared complication, but only a small fraction of CAA results in severe bleeding. On the hand the non-mechanical consequences in cerebrovascular regulation are prevalent and may be even more deleterious. Studies of animal models have provided strong evidence linking the vasoactive A beta 1-40, the main species found in CAA, to disturbances in endothelial-dependent factors, disrupting cerebrovascular regulation Here, we aimed to review experimental findings regarding the non-mechanical consequences of CAA for cerebrovascular regulation and discuss the implications of these results to clinical practice. (C) 2012 Elsevier Inc. All rights reserved.

Arterial Spin Labeling Measurements of Cerebral Perfusion Territories in Experimental Ischemic Stroke

Collateral circulation, defined as the supplementary vascular network that maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one important defense mechanism of the brain against ischemic stroke. In the present study, continuous arterial spin labeling (CASL) was used to quantify CBF and obtain perfusion territory maps of the major cerebral arteries in spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Results show that both WKY and SHR have complementary, yet significantly asymmetric perfusion territories. Right or left dominances were observed in territories of the anterior (ACA), middle and posterior cerebral arteries, and the thalamic artery. Magnetic resonance angiography showed that some of the asymmetries were correlated with variations of the ACA. The leptomeningeal circulation perfusing the outer layers of the cortex was observed as well. Significant and permanent changes in perfusion territories were obtained after temporary occlusion of the right middle cerebral artery in both SHR and WKY, regardless of their particular dominance. However, animals with right dominance presented a larger volume change of the left perfusion territory (23 +/- 9%) than animals with left dominance (7 +/- 5%, P<0.002). The data suggest that animals with contralesional dominance primarily safeguard local CBF values with small changes in contralesional perfusion territory, while animals with ipsilesional dominance show a reversal of dominance and a substantial increase in contralesional perfusion territory. These findings show the usefulness of CASL to probe the collateral circulation.

Cerebral White Matter Oxidation and Nitrosylation in Young Rodents With Kaolin-Induced Hydrocephalus

Hydrocephalus is associated with reduced blood flow in periventricular white matter. To investigate hypoxic and oxidative damage in the brains of rats with hydrocephalus, kaolin was injected into the cisterna magna of newborn 7- and 21-day-old Sprague-Dawley rats, and ventricle size was assessed by magnetic resonance imaging at 7, 21, and 42 days of age. In-situ evidence of hypoxia in periventricular capillaries and glial cells was shown by pimonidazole hydrochloride binding. Biochemical assay of thiobarbituric acid reaction and immunohistochemical detection of malondialdehyde and 4-hydroxy-2-nonenal indicated the presence of lipid peroxidation in white matter. Biochemical assay of nitrite indicated increased nitric oxide production. Nitrotyrosine immunohistochemistry showed nitrosylated proteins in white matter reactive microglia and astrocytes. Activities of the antioxidant enzymes catalase and glutathione peroxidase were not increased, and altered hypoxia-inducible factor 1 alpha was not detected by quantitative reverse transcription-polymerase chain reaction. Cerebral vascular endothelial growth factor expression determined by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay was not changed, but vascular endothelial growth factor immunoreactivity was increased in reactive astrocytes of hydrocephalic white matter. To determine if nitric oxide synthase is involved in the pathogenesis, we induced hydrocephalus in 7-day-old wild-type and neuronal nitric oxide synthase-deficient mice. At 7 days, the wild-type and mutant mice exhibited equally severe ventriculomegaly and no behavioral differences, although increased glial fibrillary acidic protein was less in the mutant mice. We conclude that hypoxia, via peroxidation and nitrosylation, contributes to brain changes in young rodents with hydrocephalus and that compensatory mechanisms are negligible.

Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats

Cyclosporine (CsA) remains an important immunosuppressant for transplantation and for treatment of autoimmune diseases. The most troublesome side effect of CsA is renal injury. Acute CsA-induced nephrotoxicity is characterized by reduced renal blood flow (RBF) and glomerular filtration rate (GFR) due to afferent arteriole vasoconstriction. Annexin A1 (ANXA1) is a potent anti-inflammatory protein with protective effect in renal ischemia/reperfusion injury. Here we study the effects of ANXA1 treatment in an experimental model of acute CsA nephrotoxicity. Salt-depleted rats were randomized to treatment with VH (vehicles 1 mL/kg body weight/day), ANXA1 (Ac2-26 peptide 1 mg/kg body weight/day intraperitoneally), CsA (20 mg/kg body weight/day subcutaneously) and CsA + ANXA1 (combination) for seven days. We compared renal function and hemodynamics, renal histopathology, renal tissue macrophage infiltration and renal ANXA1 expression between the four groups. CsA significantly impaired GFR and RBF, caused tubular dilation and macrophage infiltration and increased ANXA1 renal tissue expression. Treatment with ANXA1 attenuated CSA-induced hemodynamic changes, tubular injury and macrophage infiltration. ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsA nephrotoxicity model.

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle

Background: Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). Methods: We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 mu g/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 mu g/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 mu L) injection into the 4th V. Results: Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. Conclusion: We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity.

Visual impairment in children with spastic cerebral palsy measured by psychophysical and electrophysiological grating acuity tests

Background: This study measured grating visual acuity in 173 children between 6-48 months of age who had different types of spastic cerebral palsy (CP). Method: Behavioural acuity was measured with the Teller Acuity Cards (TAC) using a staircase psychophysical procedure. Electrophysiological visual acuity was estimated using the sweep VEP (sVEP). Results: The percentage of children outside the superior tolerance limits was 44 of 63 (69%) and 50 of 55 (91%) of tetraplegic, 36 of 56 (64%) and 42 of 53 (79%) of diplegic, 10 of 48 (21%) and 12 of 40 (30%) of hemiplegic for sVEP and TAC, respectively. For the sVEP, the greater visual acuity deficit found in the tetraplegic group was significantly different from that of the hemiplegic group (p < 0.001). In the TAC procedure the mean visual acuity deficits of the tetraplegic and diplegic groups were significantly different from that of hemiplegic group (p < 0.001). The differences between sVEP and TAC means of visual acuity difference were statistically significant for the tetraplegic (p < 0.001), diplegic (p < 0.001), and hemiplegic group (p = 0.004). Discussion: Better visual acuities were obtained in both procedures for hemiplegic children compared to diplegic or tetraplegic. Tetraplegic and diplegic children showed greater discrepancies between the TAC and sVEP results. Inter-ocular acuity difference was more frequent in sVEP measurements. Conclusions: Electrophysiologically measured visual acuity is better than behavioural visual acuity in children with CP.

Distinct placental malaria pathology caused by different Plasmodium berghei lines that fail to induce cerebral malaria in the C57BL/6 mouse

Background: Placental malaria (PM) is one major feature of malaria during pregnancy. A murine model of experimental PM using BALB/c mice infected with Plasmodium berghei ANKA was recently established, but there is need for additional PM models with different parasite/host combinations that allow to interrogate the involvement of specific host genetic factors in the placental inflammatory response to Plasmodium infection. Methods: A mid-term infection protocol was used to test PM induction by three P. berghei parasite lines, derived from the K173, NK65 and ANKA strains of P. berghei that fail to induce experimental cerebral malaria (ECM) in the susceptible C57BL/6 mice. Parasitaemia course, pregnancy outcome and placenta pathology induced by the three parasite lines were compared. Results: The three P. berghei lines were able to evoke severe PM pathology and poor pregnancy outcome features. The results indicate that parasite components required to induce PM are distinct from ECM. Nevertheless, infection with parasites of the ANKA Delta pm4 line, which lack expression of plasmepsin 4, displayed milder disease phenotypes associated with a strong innate immune response as compared to infections with NK65 and K173 parasites. Conclusions: Infection of pregnant C57BL/6 females with K173, NK65 and ANKA Delta pm4 P. berghei parasites provide experimental systems to identify host molecular components involved in PM pathogenesis mechanisms.

Functional capacity and assistance from the caregiver during daily activities in Brazilian children with cerebral palsy

Abstract Background Cerebral Palsy (CP) presents changes in posture and movement as a core characteristic, which requires multiprofessional clinical treatments during children’s habilitation or rehabilitation. Besides clinical treatment, it is fundamental that professionals use evaluation systems to quantify the difficulties presented to the individual and their families in their daily lives. We aimed to investigate the functional capacity of individuals with CP and the amount of assistance required by the caregiver in day-to-day activities. Methods Twenty patients with CP, six-year-old on average, were evaluated. The Pediatric Evaluation Inventory of Incapacities was used (PEDI - Pediatric Evaluation Disability Inventory), a system adapted for Brazil that evaluates child's dysfunction in three 3 dimensions: self-care, mobility and social function. To compare the three areas, repeated measures analysis of variance (ANOVA) were used. Results We found the following results regarding the functional capacity of children: self-care, 27.4%, ±17.5; mobility, 25.8%, ±33.3 and social function, 36.3%, ±27.7. The results of the demand of aid from the caregiver according to each dimension were: self-care, 9.7%, ±19.9; mobility, 14.1%, ± 20.9 and social function, 19.8%, ±26.1. Conclusion We indicated that there was no difference between the performance of the subjects in areas of self-care, mobility and social function considering the functional skills and assistance required by the caregiver.