Cerebral Palsy

Estrogen receptor (ER)-mediated neuroprotection has been demonstrated in both in vitro and in vivo model systems. Two types of estrogen receptors, ERalpha and ERbeta, are the major mediators of the biological functions of estrogens. In the hippocampus, ERbeta is prevalent over ERalpha. Recently, we reported that during the final phase of lactation there is a neuroprotective mechanism in the hippocampus of the adult female rat against neuronal damage induced by systemic kainic acid administration vs. virgin (metestrus) rats. In this study, we assessed differential ER expression and localization in CA1, CA3 and dentate gyrus regions of dorsal hippocampus of metestrus and lactating adult rats at day 19 of lactation, during basal conditions (metestrus and L19, respectively) and 24h after systemic kainate administration. ERs were assessed by western blot and immunohistochemistry. We found a significant increase in the expression of ERs in the hippocampus during lactation as compared with metestrus. ERbeta was significantly increased in the CA1 and CA3 of lactating rats after the kainic acid insult. In addition, we observed a relocalization of ERbeta from the cytoplasm to the nucleus of neuronal cells. Our results suggest that there is a strong correlation between expression of ERs, especially ERbeta, in lactating CA1 and CA3 hippocampus regions in response to kainate administration, and neuroprotection observed during this reproductive period. This may be one of the mechanisms involved in the protection of the maternal brain to ensure offspring survival.

BACKGROUND: We evaluated midterm results of endovascular management of traumatic aortic isthmic ruptures. METHODS: Between 2001 and 2008, 10 patients (seven males, mean age 38 years) underwent endovascular treatment of an acute aortic rupture. Eight procedures were emergent, with four cases of hemodynamic instability with Glasgow scores of 3, 5, and 7. Associated traumas were severe brain, liver, and pelvic bone injuries. All procedures were performed with transoesophageal echocardiography monitoring. We used two AneuRx and nine Medtronic Talent or Valiant stent grafts. RESULTS: All patients survived their traumatic isthmic rupture. In nine patients, stent-graft deployment was successful. One patient experienced a distal migration needing a laparotomy and deployment of an additional new thoracic stent graft. The mean intensive care unit stay was 48 hr (range 24-168). The mean hospital stay was 11 days (range 8-43). All patients were controlled clinically and by contrast computed tomography (CT) according to the EUROSTAR protocol. There were no endoleaks, stent graft-related complications, or late deaths during a mean follow-up of 49 months. The control CT showed a lack of apposition of the proximal part of the stent graft at the inner curve of the aortic arch in three patients. CONCLUSION: The midterm results of endovascular treatment of acute traumatic aortic isthmic rupture are encouraging and compare favorably to the surgical approach. Late follow-up is required to exclude possible stent-graft complications, especially in young patients with angulated aortic arches.

INTRODUCTION: Post-traumatic locked-in syndrome may be particularly difficult to recognize, especially when it follows a state of coma and presents the clinical feature of a “total” locked-in syndrome. PATIENT AND METHODS: A 56-year-old male with a closed head injury was admitted in intensive care unit (ICU) with GCS=4 (V1, M2, E1). Computed tomography (CT) scan disclosed a limited subarachnoid haemorrhage in the sylvian region without any brain oedema or ventricular shift. The GCS did not change until day6. At the same time EEG showed a reactivity to acoustic stimuli consisting in the paradoxical appearance of a posterior rhythm in alpha range (10-12c/s), blocked by passive eye opening. Early cortical components (N20-P25) of somatosensory evoked potentials were normal on both hemispheres; middle components were also clearly evident. Magnetic resonance imaging of the brain showed both diffuse and midbrain axonal injuries, particularly in a strategic lesion involving both cerebral peduncles. Event related potentials showed N2 and P3 components to stimulation by rare tones. CONCLUSIONS: A comprehensive multimodal neurophysiological approach, using the more informative tests and the proper time of recording, should be included in protocols for patients with severe head trauma, in order to establish the actual patient’s clinical state and to avoid that a locked-in syndrome state be mistaken for prolonged coma, vegetative state, minimally conscious state or akinetic mutism. Neurophysiological evaluation before discharge from ICU can be a baseline evaluation useful for the follow-up of low-responsive patients in the neuro-rehabilitation unit.

AIMS: To monitor acute brain injury in the neurological intensive care unit (NICU), we used EEG and somatosensory evoked potentials (SEP) in combination to achieve more accuracy in detecting brain function deterioration. METHODS: Sixty-eight patients (head trauma and intracranial hemorrhage; GCS<9) were monitored with continuous EEG-SEP and intracranial pressure monitoring (ICP). RESULTS: Fifty-five patients were considered "stable" or improving, considering the GCS and CT scan: in this group, SEP didn't show significant changes. Thirteen patients showed neurological deteriorations and, in all patients, cortical SEP showed significant alterations (amplitude decrease>50% often till complete disappearance). SEP deterioration anticipated ICP increase in 30%, was contemporary in 38%, and followed ICP increase in 23%. Considering SEP and ICP in relation to clinical course, all patients but one with ICP less than 20mmHg were stable, while the three patients with ICP greater than 40mmHg all died. Among the 26 patients with ICP of 20-40mmHg, 17 were stable, while nine showed clinical and neurophysiological deterioration. Thus, there is a range of ICP values (20-40mmHg) were ICP is scarcely indicative of clinical deterioration, rather it is the SEP changes that identify brain function deterioration. Therefore, SEP have a twofold interest with respect to ICP: their changes can precede an ICP increase and they can constitute a complementary tool to interpret ICP trends. It has been very important to associate SEP and EEG: about 60% of our patients were deeply sedated and, because of their relative insensitivity to anesthetics, only SEP allowed us to monitor brain damage evolution when EEG was scarcely valuable. CONCLUSIONS: We observed 3% of nonconvulsive status epilepticus compared to 18% of neurological deterioration. If the aim of neurophysiological monitoring is to "detect and protect", it may not be limited to detecting seizures, rather it should be able to identify brain deterioration, so we propose the combined monitoring of EEG with SEP.

The concept of reserve has been proposed to account for the disjunction between the degree of brain damage and its clinical outcome. This paper attempts to produce a coherent theoretical account the reserve in general and of cognitive reserve in particular. It reviews epidemiologic data supporting the concept of cognitive reserve, with a particular focus of its implications for aging and dementia. It then focuses on methodologic issues that are important when attempting to elucidate the neural underpinnings of cognitive reserve using imaging studies, and reviews some of our group’s work in order to demonstrate these issues.

Microglia normally exist in a resting state characterized by a ramified morphology, and are responsible for immune surveillance in the CNS. However, the resting microglia rapidly transform towards an activated phenotype in response to brain injury or immunological stimuli. In certain pathological conditions, the unregulated response or over-activation of microglia can provoke severe neuronal damage. Here, we have investigated whether Semaphorin4D (Sema4D/CD100) could function as a potential factor to control activation. Microglia were cultured, activated by bacterial endotoxin lipopolysaccharide (LPS) and then, exposed to Sema4D/CD100 or conditioned medium. We found that Sema4D/CD100 negatively controlled LPS-induced morphological activation. Moreover, intracerebral injection of LPS induced abundant microglial activated forms in mice lacking Sema4D/CD100. Sema4D/CD100 also inhibited other relevant aspects of cell activation. Treatment with Sema4D/CD100 inhibited the production of nitrites and LPS-induced microglia migration. We also provide evidence that LPS markedly upregulated Plexin-B1 expression in microglia and Sema4D/CD100 stimulated RhoA-activation in LPS-activated microglia. Taken together, these findings suggest a novel role of Sema4D/CD100 in the regulation of microglia activation providing a valuable neuroprotective tool to the CNS.

PURPOSE: To investigate postnatal development of left ventricular (LV) cardiac function and myocardium structure. MATERIALS AND METHODS: In vivo cardiac MR and ex vivo diffusion tensor imaging (DTI) were performed in normal Sprague-Dawley rats at postnatal day 2, 4, 7, 14, 21, 28, and 56 (N = 6 per group). RESULTS: Morphologically, LV size increased with age. Functionally, stroke volume and cardiac output increased. Heart rate increased gradually and became stable after day 14. On average, ejection fraction increased within the first 4 days, decreased at day 7, gradually increased until day 21, and became stable afterward. Structurally, double-helical myocardial structure was found as early as day 2. Myocardial fiber parameters, described by fractional anisotropy, mean apparent diffusion coefficient, and axial diffusivity, increased within the first 4 days. Then radial diffusivity increased until day 7 while other parameters decreased up to day 56. CONCLUSION: Postnatal heart development was documented by MRI. DTI findings are in agreement with the two known stages of early postnatal growth: hyperplasia and hypertrophy. These results can serve as the baselines for study of postnatal heart developmental abnormalities. They also demonstrate the ability of DTI to reveal microstructural alterations in myocardium. J. Magn. Reson. Imaging 2009. (c) 2009 Wiley-Liss, Inc.

Phase contrast magnetic resonance imaging is performed to produce flow fields of blood in the heart. The aim of this study is to demonstrate the state of change in swirling blood flow within cardiac chambers and to quantify it for clinical analysis. Velocity fields based on the projection of the three dimensional blood flow onto multiple planes are scanned. The flow patterns can be illustrated using streamlines and vector plots to show the blood dynamical behavior at every cardiac phase. Large-scale vortices can be observed in the heart chambers, and we have developed a technique for characterizing their locations and strength. From our results, we are able to acquire an indication of the changes in blood swirls over one cardiac cycle by using temporal vorticity fields of the cardiac flow. This can improve our understanding of blood dynamics within the heart that may have implications in blood circulation efficiency. The results presented in this paper can establish a set of reference data to compare with unusual flow patterns due to cardiac abnormalities. The calibration of other flow-imaging modalities can also be achieved using this well-established velocity-encoding standard.

It has been established that atherosclerotic coronary artery disease is more frequent and more severe in diabetic compared to non-diabetic subjects, but the reason for the excess risk of developing coronary macroangiopathy in diabetes remains incompletely characterized. Various biochemical mechanisms speculated to being at the “heart” of diabetic cardiac and coronary macroangiopathy are reviewed in the present article. In doing so, this article presents evidence that the labyrinthine interactions of hyperglycemia, insulin resistance, and dyslipidemia in diabetes result in a pro-atherogenic phenotype. Furthermore, the diabetic milieu yields a complex (dys)metabolic environment characterized by chronic inflammation, procoagulability, impaired fibrinolysis, neovascularization abnormalities, and microvascular defects that cumulatively alter blood rheology, artery structure, and homeostasis of the endothelium. The contributory influences of these factors in the pathophysiology of coronary artery disease in diabetes are also discussed.

Hereditary protein S (PS) deficiency is an autosomal disorder caused by mutations in the PS gene (PROS1). Conventional PCR-based mutation detection identifies PROS1 point mutations in approximately 50% of the cases. To verify if gross copy number variations (CNVs) are often present in point mutation-negative hereditary PS deficiency we used multiplex ligation-dependent probe amplification (MLPA) as a detection tool in samples from individuals with a high probability of having true PS deficiency. To this end, DNA samples from nine PS deficient probands with family members (seven type I and two type III) and nine isolated probands (three type I and six type III), in whom PROS1 mutations were not found by DNA sequencing, were evaluated. An independent quantitative PCR (qPCR) was performed to confirm the findings of the MLPA assay. Family members were also tested when DNA was available. Gross abnormalities of PROS1 were found in six out of eighteen probands. In three probands complete deletion of the gene was detected. Two probands had a partial deletion involving different parts of the gene (one from exon 4 through 9 and another from exon 9 through 11). One family showed a duplication of part of PROS1. qPCR analysis was in accordance with these results. In conclusion, this study substantiates that gross gene abnormalities in PROS1 are relatively common in hereditary PS deficient patients and that MLPA is a useful tool for direct screening of CNVs in PROS1 point mutation-negative individuals.