An unusual presentation of varicella zoster virus with acute cerebellitis and SIADH without a rash

We report a case of varicella-zoster virus (VZV) infection with acute cerebellitis and encephalitis with associated Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in an elderly man presenting with acute cerebellar ataxia without antecedent rash. Cerebrospinal fluid examination (CSF) revealed a mononuclear pleocytosis, high protein, normal glucose, positive for VZV polymerase chain reaction (PCR). Early acyclovir treatment is beneficial for acute VZV cerebellitis. Clinicians should consider infectious Central Nervous System (CNS) causes for presentations of acute cerebellar ataxia in adult patients, particularly if there is an accompanying clouded sensorium.     

新型脑白质病变动物模型及其脑小血管的病理学研究

目的建立一个新型的具有高血压及脑小血管病理改变的脑白质病变(white matter lesions,WMLs)动物模型。方法 13只雄性Sprague-Dawley大鼠,随机分为假手术组(n=6)与易卒中型肾血管性高血压-改良的2VO组(stroke-prone renovascular hypertensive rat-modified 2 vessel occlusion RHRSP/Modified 2VO)(n=7),RHRSP/Modified 2VO组先行双肾双夹术制作RHRSP模型,12周后间隔1周先后夹闭双侧颈总动脉。双肾双夹术后20周对大鼠进行水迷宫试验观察大鼠是否存在空间记忆功能的受损,组织病理学检测观察是否存在脑白质病变及相应的脑小血管病理学改变。结果双肾双夹术后12周,RHRSP/Modified 2VO组7只大鼠收缩压均大于180 mm Hg;水迷宫实验:RHRSP/Modified 2VO组的逃避潜伏期较假手术组明显升高(P0.05),穿越平台次数及原平台象限停留时间比较假手术组明显降低[(2.5±1.05 vs.5±1.67);(28.04%±14.13%vs.49.69%±13.12%)],差异具有统计学意义(P0.05);RHRSP/Modified 2VO组脑白质病变的分级明显高于假手术组(2.17±0.75 vs.0.33±0.52),差异具有统计学意义(P0.05),且RHRSP/Modified 2VO大鼠存在脑小血管的病理改变(小动脉管壁增厚、血脑屏障破坏及静脉胶原沉积)。结论 RHRSP/Modified 2VO是适用的WMLs动物模型,可用于探究WMLs的发病机制及治疗靶点。     

Orofacial dyskinesias and dystonia in rats infected with Borna disease virus; a model for tardive dyskinetic syndromes.

The neurochemical and lesion effects of Borna disease virus infection in rats result in a syndrome with phenotypic and pharmacological similarities to tardive dyskinesia.     

可生物降解的聚乳酸阿霉素对胶质瘤缓释化疗系统的研制及实验研究

目的研制一种可生物降解的肿瘤间质内缓释化疗系统,提高和维持胶质瘤内药物浓度,降低全身毒副作用。方法应用聚乳酸和盐酸阿霉素制成聚乳酸－阿霉素缓释片,经高效液相色谱仪测定其缓释速率,动物实验检测其生物相容性、体内杀瘤效果和全身毒副作用。结果　该缓释系统７天可将Ｃ６胶质瘤动物模型皮下肿瘤全部杀灭,骨髓抑制较同剂量静脉给药减少５０％,且程度较轻,无死亡率,无胃肠道反应,脱毛现象减少６０％,对正常组织细胞无刺激损害。结论聚乳酸－阿霉素缓释系统杀瘤效果肯定,毒副作用少,具有良好的生物相容性。     

Acute neuroinflammation in Lewis rats — A model for acute multiple sclerosis relapses

Animal models of experimental allergic encephalomyelitis (EAE) are the most commonly used animal models for studying the pathogenesis of human multiple sclerosis (MS) as well as for target validation and compound characterization in pharmacology. By using an EAE model in Lewis rats, we focus on its neuroimmunological characterization with special attention to disease-involved cytokines, chemokines, and adhesion molecules. Furthermore, we used MR imaging to investigate macrophage infiltration and ICAM-1 expression in lesional spinal cord. Overall, due to its inflammatory character, this model is suggested to be used in early drug discovery particularly directed against acute inflammatory processes.     

Wistar–Kyoto rats as an animal model of anxiety vulnerability: Support for a hypervigilance hypothesis

Inbred Wistar–Kyoto (WKY) rats have been proposed as a model of anxiety vulnerability as they display behavioral inhibition and a constellation of learning and reactivity abnormalities relative to outbred Sprague–Dawley (SD) rats. Together, the behaviors of the WKY rat suggest a hypervigilant state that may contribute to its anxiety vulnerability. To test this hypothesis, open-field behavior, acoustic startle, pre-pulse inhibition and timing behavior were assessed in WKY and Sprague–Dawley (SD) rats. Timing behavior was evaluated using a modified version of the peak-interval timing procedure. Training and testing of timing first occurred without audio–visual (AV) interference. Following this initial test, AV interference was included on some trials. Overall, WKY rats took much longer to leave the center of the arena, made fewer line crossings, and reared less, than did SD rats. WKY rats showed much greater startle responses to acoustic stimuli and significantly greater pre-pulse inhibition than did the SD rats. During timing conditions without AV interference, timing accuracy for both strains was similar; peak times for WKY and SD rats were not different. During interference conditions, however, the timing behavior of the two strains was very different. Whereas peak times for SD rats were similar between non-interference and interference conditions, peak times for WKY rats were shorter and response rates higher in interference conditions than in non-interference conditions. The enhanced acoustic startle response, greater prepulse inhibition and altered timing behavior with audio–visual interference supports a characterization of WKY strain as hypervigilant and provides further evidence for the use of the WKY strain as a model of anxiety vulnerability.     

Methylphenidate affects striatal dopamine differently in an animal model for attention-deficit/hyperactivity disorder—the spontaneously hypertensive rat

The spontaneously hypertensive rat (SHR) is used as a model for attention-deficit/hyperactivity disorder (ADHD) because it has behavioural characteristics (hyperactivity, impulsiveness, poorly sustained attention) similar to those of ADHD. ADHD children have been shown to have reduced striatal activation in certain tasks. SHR have reduced striatal dopamine release in response to electrical stimulation. The present study set out to investigate possible long-term effects of methylphenidate treatment on dopaminergic function in striatal slices of SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. Methylphenidate treatment (3 mg/kg daily for 14 days) did not normalize the decreased electrically-stimulated release of [³H]dopamine from SHR caudate-putamen slices nor did it affect postsynaptic D₂ receptor function. However, the second electrical stimulus caused a relatively greater release of [³H]dopamine from caudate-putamen slices of methylphenidate-treated SHR than from vehicle-treated SHR, suggesting that presynaptic mechanisms controlling dopamine release had been altered. Interestingly, [³H]dopamine release from WKY caudate-putamen slices in response to D₂ autoreceptor blockade by the antagonist, sulpiride, was selectively increased by methylphenidate treatment. This effect was not seen in SHR possibly because D₂ autoreceptor function had already been up-regulated. The results show that methylphenidate is unable to enhance D₂ autoreceptor function in SHR.     

Changes in gene expression after phencyclidine administration in developing rats: a potential animal model for schizophrenia

Repeated administration of phencyclidine (PCP), an N-methyl-d-aspartate (NMDA) receptor antagonist, during development, may result in neuronal damage that leads to behavioral deficits in adulthood. The present study examined the potential neurotoxic effects of PCP exposure (10 mg/kg) in rats on postnatal days (PNDs) 7, 9 and 11 and the possible underlying mechanism(s) for neurotoxicity. Brain tissue was harvested for RNA extraction and morphological assessments. RNA was collected from the frontal cortex for DNA microarray analysis and quantitative RT-PCR. Gene expression profiling was determined using Illumina Rat Ref-12 Expression BeadChips containing 22,226 probes. Based on criteria of a fold-change greater than 1.4 and a P-value less than 0.05, 19 genes including NMDAR1 (N-methyl-d-aspartate receptor) and four pro-apoptotic genes were up-regulated, and 25 genes including four anti-apoptotic genes were down-regulated, in the PCP-treated group. In addition, the schizophrenia-relevant genes, Bdnf (Brain-derived neurotrophic factor) and Bhlhb2 (basic helix-loop-helix domain containing, class B, 2), were significantly different between the PCP and the control groups. Quantitative RT-PCR confirmed the microarray results. Elevated neuronal cell death was further confirmed using Fluoro-Jade C staining. These findings support the hypothesis that neurodegeneration caused by PCP occurs, at least in part, through the up-regulation of NMDA receptors, which makes neurons possessing these receptors more vulnerable to endogenous glutamate. The changes in schizophrenia-relevant genes after repeated PCP exposure during development may provide important information concerning the validation of an animal model for this disorder.     

Neurodegeneration induced by reversed microdialysis of NMDA; a quantitative model for excitotoxicity in vivo

This study characterizes a quantifiable in vivo model of excitotoxicity. In halothane anesthetized rats, microdialysis probe was implanted into somatosensory cortex/striatum and perfused by various concentrations (1, 10, 50 and 100 mmol/l) of N-methyl- -aspartate (NMDA) for 20 min. After 24 h, histological quantification confirmed that NMDA produced a concentration-dependent excitotoxic lesion. With 10 mmol/l NMDA, coadministration of magnesium reduced significantly, and 2-amino-5-phosphonovalerate blocked completely the development of excitotoxic injury.     

NIRS‐measured oxy‐ and deoxyhemoglobin changes associated with EEG spike‐and‐wave discharges in a genetic model of absence epilepsy: The GAERS

Purpose: Absence epilepsy may be severe and is frequently accompanied by cognitive delay, yet its metabolic/hemodynamic aspects have not been established. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an isomorphic, predictive, and homologous model of human absence epilepsy. We studied hemodynamic changes related to generalized spike‐and‐wave discharges (GSWDs) in GAERS by using a technique with high temporal resolution: near‐infrared spectroscopy (NIRS). We hypothesized that conflicting results from other techniques might be due to the averaging of a biphasic response such as the one we described in children. Methods: NIRS is particularly suitable for monitoring changes in the concentrations of oxy‐, deoxy‐, and total hemoglobin (HbO₂, HHb, and HbT), using the specific absorption properties of living tissues in the near infrared range. We obtained concomitant high quality electroencephalography (EEG)–NIRS recordings in six GAERS (total of 444 seizures), and tested whether the discharges were related to changes in cardiac or respiration rates. Results: The onset of GSWDs was preceded by a deactivation, followed by an activation that was possibly due to seizure‐suppression mechanisms. The end was marked by a deactivation. The onset of GSWDs was associated with a decrease and the end with a brief increase in respiratory rate. Discussion: Our results differ partially from those of previous studies on hemodynamic aspects of GSWDs (many of which describe a simple deactivation), probably due to differences in temporal resolution and data processing; however, they are consistent with metabolic studies, functional magnetic resonance imaging (fMRI) studies on WAG/Rij rats, and some results in children with absence epilepsy.     

Intact intracortical microstimulation (ICMS) representations of rostral and caudal forelimb areas in rats with quinolinic acid lesions of the medial or lateral caudate-putamen in an animal model of Huntington's disease

Neurotoxic, cell-specific lesions of the rat caudate-putamen (CPu) have been proposed as a model of human Huntington's disease and as such impair performance on many motor tasks, including skilled forelimbs tasks such as reaching for food. Because the CPu and motor cortex share reciprocal connections, it has been proposed that the motor deficits are due in part to a secondary disruption of motor cortex. The purpose of the present study was to examine the functionality of the motor cortex using intracortical microstimulation (ICMS) following neurotoxic lesions of the CPu. ICMS maps have been shown to be sensitive indicators of motor skill, cortical injury, learning, and experience. Long-evans hooded rats received a sham, a medial, or a lateral CPu lesion using the neurotoxin, quinolinic acid (2,3-pyridinedicarboxylic acid). Two weeks later the motor cortex was stimulated under light ketamine anesthesia. Neither lateral nor medial lesions of the CPu altered the stimulation threshold for eliciting forelimb movements, the type of movements elicited, or the size of the rostral forelimb (RFA) and caudal forelimb areas (CFA) from which movements were elicited. The preservation of ICMS forelimb movement representations (the forelimb map) in rats with cell-specific CPu lesions suggests motor impairments following lesions of the lateral striatum are not due to the disruption of the motor map. Therefore, the impairments that follow striatal cell loss are due either to alterations in circuitry that is independent of motor cortex or to alterations in circuitry afferent to the motor cortex projections.     

Histologic evidence for a toxic polyneuropathy due to exposure to 2,3,7,8 — tetrachlorodibenzo-p-dioxin (TCDD) in rats

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a considerable environmental hazard in industrial societies. Its toxic effects on animals and humans are numerous, but little is known about its neurotoxicity. We studied the neurotoxic effects of TCDD in 80 male, adult Wistar rats. The substance was dissolved in corn oil and a single dose injected intraperitoneally (8.8 μg, 6.6 μg, 4.4μg or 2.2μg/kg). Neurophysiological examinations proved a dose-related, statistically significant slowing of sensory and motor conduction velocities. Ten months after the application of TCDD peripheral nerves showed a progressive, and proximally accentuated neuropathy. The extent of changes, however, differed remarkably between individual animals. Our data indicate that TCDD caused a toxic polyneuropathy in rats.     

Changes in response to metrazole during fever in juvenile rats; a new model for febrile convulsions?

ABSTRACT— Previous models for febrile convulsions have used environmentally induced hyperthermia as the stimulus to induce convulsions. Changes in response to metrazole during yeast-induced fever in juvenile rats are reported here. Animals were more susceptible to metrazole during the rising phase of fever but showed some resistance to its convulsant effects once the fever was established and following defervescence. It is suggested that this may form the basis of a physiologically more appropriate model for the study of the pathogenesis of febrile convulsions.     

Neonatal intrahippocampal injection of lipopolysaccharide induces deficits in social behavior and prepulse inhibition and microglial activation in rats: Implication for a new schizophrenia animal model

Several lines of evidence have suggested that the dysregulation of immune system is involved in the pathogenesis of schizophrenia. Microglia are the resident macrophage of the brain and the major player in innate immunity in the brain. We hypothesized that microglia activation may be closely associated with the neuropathology of schizophrenia. Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (PD7), and they were separately treated with saline or minocycline for consecutive 3 days. Behavioral changes (locomotor activity, social interaction and prepulse inhibition) were examined in adulthood, and the number of microglia was assessed using immunohistochemistry at PD9, PD21 and PD67. The adult rats in LPS-injected group showed obvious behavioral alterations (deficits in social behavior and prepulse inhibition) and a persistently dramatic increase of number of activated microglial cells in the hippocampus, cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, pretreatment with minocycline could significantly rescue the behavioral deficits and prevent microglia activation. Our results suggest that neonatal intrahippocampal LPS injection may serve as a potential schizophrenia animal model, and inhibition of microglia activation may be a potential treatment strategy for schizophrenia.     

Comparison of the antiepileptogenic effects of an early long‐term treatment with ethosuximide or levetiracetam in a genetic animal model of absence epilepsy

Purpose: Epilepsy is a heterogeneous syndrome characterized by recurrent, spontaneous seizures; continuous medication is, therefore, necessary, even after the seizures have long been suppressed with antiepileptic drug (AED) treatments. The most disturbing issue is the inability of AEDs to provide a persistent cure, because these compounds generally suppress the occurrence of epileptic seizures without necessarily having antiepileptogenic properties. The aim of our experiments was to determine, in the WAG/Rij model of absence epilepsy, if early long‐term treatment with some established antiabsence drugs might prevent the development of seizures, and whether such an effect could be sustained. Methods: WAG/Rij rats were treated for ～3.5 months (starting at 1.5 months of age, before seizure onset) with either ethosuximide (ETH; drug of choice for absence epilepsy) or levetiracetam (LEV; a broad‐spectrum AED with antiabsence and antiepileptogenic properties). Results: We have demonstrated that both drugs are able to reduce the development of absence seizures, exhibiting antiepileptogenic effects in this specific animal model. Discussion: These findings suggest that absence epilepsy in this strain of rats very likely follows an epileptogenic process during life and that early therapeutic intervention is possible, thereby opening a new area of research for absence epilepsy and AED treatment strategies.