Intrathecal delivery of IFN-gamma protects C57BL/6 mice from chronic-progressive experimental autoimmune encephalomyelitis by increasing apoptosis of central nervous system-infiltrating lymphocytes.
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The exclusive detrimental role of proinflammatory cytokines in demyelinating diseases of the CNS, such as multiple sclerosis, is controversial. Here we show that the intrathecal delivery of an HSV-1-derived vector engineered with the mouse IFN-gamma gene leads to persistent (up to 4 wk) CNS production of IFN-gamma and inhibits the course of a chronic-progressive form of experimental autoimmune encephalomyelitis (EAE) induced in C57BL/6 mice by myelin oligodendrocyte glycoprotein (MOG)(35-55). Mice treated with the IFN-gamma-containing vector before EAE onset showed an earlier onset but a milder course of the disease compared with control mice treated with the empty vector. In addition, 83% of IFN-gamma-treated mice completely recovered within 25 days post immunization, whereas control mice did not recover up to 60 days post immunization. Mice treated with the IFN-gamma-containing vector within 1 wk after EAE onset partially recovered from the disease within 25 days after vector injection, whereas control mice worsened. Recovery from EAE in mice treated with IFN-gamma was associated with a significant increase of CNS-infiltrating lymphocytes undergoing apoptosis. During the recovery phase, the mRNA level of TNFR1 was also significantly increased in CNS-infiltrating cells from IFN-gamma-treated mice compared with controls. Our results further challenge the exclusive detrimental role of IFN-gamma in the CNS during EAE/multiple sclerosis, and indicate that CNS-confined inflammation may induce protective immunological countermechanisms leading to a faster clearance of encephalitogenic T cells by apoptosis, thus restoring the immune privilege of the CNS. (+info)
Clinical usefulness of magnetic resonance cisternography in patients having hemifacial spasm.
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To evaluate the usefulness of MR cisternography fourteen patients that had hemifacial spasm and 20 control patients underwent MR cisternography. All the patients with hemifacial spasm had a confirmed vascular compression after surgery. MR cisternography was performed using a 1.5-tesla superconducting MR magnet in which a 3D (dimensional) heavily T2-weighted turbo spin-echo sequence was used. In 34 randomly selected individuals, we retrospectively determined whether MR cisternography images could be used to evaluate symptoms, and what the benefits of obtaining this image was. The results were correlated with the surgical findings. The sensitivity was 100% and the specificity was 94% in all patients having a hemifacial spasm. The offending vessels were the anterior inferior cerebellar artery (AICA) in six patients cases, the posterior inferior cerebellar artery (PICA) in six, both the vertebral artery and PICA in one, and the vertebral artery in one. All the images showed good resolution and contrast, and also showed the exact correlation between the facial nerve and intracranial vessels in the multiplaner image. The findings of neurovascular compression were well correlated with the surgical findings. We believe that high-resolution 3D MR cisternography is a very useful method for evaluating the neurovascular compression in patients that have hemifacial spasm. (+info)
Cationic polymer and lipids augment adenovirus-mediated gene transfer to cerebral arteries in vivo.
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Adenovirus-mediated gene transfer to blood vessels is relatively inefficient because binding of adenovirus to vessels is limited. The authors have reported that incorporation of cationic polymer and lipids with adenovirus augments gene transfer to blood vessels ex vivo. In this study, the authors determined whether complexes of adenovirus and cations improve efficiency of gene transfer in vivo. Poly-L-lysine, lipofectamine, or lipofectin was complexed with adenovirus encoding beta-galactosidase. Optimum ratios of the cations per adenovirus were determined by gene transfer to fibroblasts. After injection of the adenovirus into the cisterna magna of anesthetized rabbits, transgene activity was greater in the adventitia of intracranial arteries and meninges after injection of the complexes than adenovirus alone. Thirty minutes after application of adenovirus with the cations, binding of adenovirus to fibroblast cells in vitro or the basilar artery in vivo (by Southern blot analysis) was augmented, which suggests that enhanced binding of virus contributes to augmentation of transgene expression. Thus, cationic polymer and lipids improve transgene expression in intracranial arteries, primarily in the adventitia, after adenovirus-mediated gene transfer in vivo. This strategy may be applicable to studies of gene transfer and eventually for gene therapy. (+info)
Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited.
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BACKGROUND AND PURPOSE: Thick cisternal clot on CT is a well-recognized risk factor for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Whether intraventricular hemorrhage (IVH) or intracerebral hemorrhage (ICH) predisposes to DCI is unclear. The Fisher CT grading scale identifies thick SAH but does not separately account for IVH or ICH. METHODS: We studied 276 consecutively admitted patients with an available admission CT scan performed within 72 hours of onset. Demographic, clinical, laboratory, and neuroimaging data were recorded, and the amount and location of SAH, IVH, and ICH on admission CT scans were quantified. The relationship between these variables and DCI was analyzed separately and in combination with multiple logistic regression. RESULTS: DCI developed in 20% of patients (54 of 276). Among SAH variables, thick clot completely filling any cistern or fissure was the best predictor of DCI (P=0.008), and among IVH variables, blood in both lateral ventricles was most predictive (P=0.001). These variables had independent predictive value for DCI in a multivariate analysis of CT findings, and both were included in a final multivariate model when evaluated in conjunction with other clinical risk factors: IVH (OR 4.1, 95% CI 1.7 to 9.8), SAH (OR 2.3, 95% CI 1.5 to 9.5), mean arterial pressure >112 mm Hg (OR 4.9, 95% CI 2.1 to 11.4), and transcranial Doppler mean velocity >140 cm/s within 5 days of hemorrhage (OR 3.8, 95% CI 1.5 to 9.5). Similar results were obtained in a repeat analysis with infarction due to vasospasm as the dependent variable. CONCLUSIONS: SAH completely filling any cistern or fissure and IVH in the lateral ventricles are both risk factors for DCI, and their risk is additive. We propose a new SAH rating scale that accounts for the independent predictive value of subarachnoid and ventricular blood for DCI. (+info)
Endotoxin as a cause of aseptic meningitis after radionuclide cisternography.
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The role of pyrogens in aseptic meningitis after radionuclide cisternography was studied by means of the Limulus test, a sensitive detector of endotoxin. During a 15-month period, 39 reactions associated with cisternography were reported. Ten samples of specific lots of the radioactive drugs implicated in 20 of these reactions were tested and all reacted strongly positive to the Limulus test. The less sensitive rabbit pyrogen test was negative for these preparations when tested on a dose-per-weight basis. Our findings apparently provide clinical evidence for the observation made in animals that endotoxin is at least 1,000 times more toxic intrathecally than intravenously. The data implicate endotoxin contamination as a cause of adverse reactions to radionuclide cisternography. We conclude that the USP pyrogen test is insufficiently sensitive for intrathecal injectables and should be supplemented by the Limulus test. (+info)
Is brain prostaglandin synthesis involved in responses to cold?
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1. Experiments with rats have suggested that prostaglandin synthesis in the C.N.S. may mediate thermoregulatory reactions to cold. This possibility was investigated in cats using two types of experiment. 2. In one series of experiments, c.s.f. collected from the cisterna magna of conscious cats exposed to a cold and a hot environment was assayed for prostaglandin-like activity. During cold exposure there was a slight increase in activity which persisted after return to neutral ambient temperature. There was no correlation between prostaglandin-like activity and rectal temperature. During the heat exposure there was no demonstrable change in activity. 3. In the second series, conscious cats were exposed to cold conditions and given intravenous injections of salicylate, paracetamol, or indomethacin, all of which inhibit prostaglandin synthesis. Indomethacin salicylate nor paracetamol caused any significant change in rectal temperature. 4. The results do not support a role for C.N.S. prostaglandin synthesis in thermoregulatory reactions to cold in cats. (+info)
Cardiovascular effects of dopamine after central administration into conscious cats.
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Dopamine (30 and 45 mug) administered intracerebroventricular (i.c.v.) to a group of 10 conscious normotensive cats caused dose-related increases in blood pressure and heart rate. In 4 of these animals the initial cardiovascular stimulant effects of i.c.v. dopamine were followed by hypotension and bradycardia. 2 alpha-Methyldopamine (30 and 45 mug i.c.v.) produced qualitatively similar responses to dopamine except that the cardiovascular stimulant effects were smaller and the secondary depressant effects somewhat more prolonged. 3 Both stimulant and depressant effects of i.c.v. dopamine and alpha-methyldopamine were greatly inhibited by autonomic ganglion blockade or by adrenergic neurone blockade. 4 The cardiovascular stimulant effects of both i.c.v. dopamine and i.c.v. alpha-methyldopamine were selectively inhibited by beta-adrenoceptor blocking agents whilst the cardiovascular depressant effects of these substances were abolished by the alpha-adrenoceptor blocker phentolamine or by the dopamine-beta-hydroxylase inhibitor disulfiram. 5 Haloperidol by either i.c.v. or the intravenous route abolished both cardiovascular stimulant and depressant effects of i.c.v. dopamine, whilst pimozide by either route inhibited only the cardiovascular stimulant effects. 6 In 2 cats, injection of dopamine into the cisterna magna produced predominantly depressant effects on the cardiovascular system except with a higher dose which induced biphasic responses. (+info)
Influence of imaging parameters on high-intensity cerebrospinal fluid artifacts in fast-FLAIR MR imaging.
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BACKGROUND AND PURPOSE: High-intensity CSF artifacts at the basal cisterns on MR images are often seen when a fast fluid-attenuated inversion recovery (FLAIR) technique is used. We investigated the influences of four optional fast-FLAIR sequence parameters on the high-intensity CSF artifacts. METHODS: A total of 377 patients (age range, 1 week to 91 years; mean 40.6 years; 186 female, 191 male) were examined with axial fast-FLAIR images obtained (TR/TE(eff)/TI, 8800/133/2200) with a 1.5-T system during 6 months. The effects of the optional addition of inferior inflow saturation (thickness, 80 mm), section flow compensation, and tailored radiofrequency (TRF) pulses, plus the choice of interleaving acquisition factors of 2 or 3, were evaluated for the presence of high-intensity CSF artifacts on the fast-FLAIR images. Two radiologists independently reviewed the fast-FLAIR images in 76 patients; afterward, a single observer reviewed the remainder of the images. RESULTS: The interobserver agreement rate in 76 cases was more than 90%. The use of TRF and/or three interleaving acquisitions resulted in a substantial reduction in the incidence of high-intensity CSF artifacts from about 80% to 40% (P <.05, two-sample two-sided Z test). Inferior inflow saturation and section flow compensation did not significantly improve image quality (P >.05). The results were consistent with the image quality ranking obtained in five healthy volunteers. CONCLUSION: The appropriate choice of sequence parameters in fast-FLAIR imaging reduces the incidence of high-intensity CSF artifacts that are frequently encountered in the presence of rapid CSF flow. (+info)