Neurological Deficit and Structural Changes in Lymphoid Structures of the Tracheal Wall in the Immediate Stage of Experimental Hemorrhagic Stroke in Rats with Different Behavioral Activity.

Specific features of neurological deficit and changes in the cellular composition of tracheal lymphoid structures during the immediate stage (day 1) of hemorrhagic stroke were studied in rats with various behavioral parameters. Modeling of hemorrhage in the left caudate nucleus of the brain was followed by the development of motor disturbances in the forelimb use asymmetry test and corner rotation paradigm. These animals preferred to use the left forelimb (ipsilateral to the side of hemorrhage) to lean on the cylinder wall. The frequency of using the right forelimb or both forelimbs was reduced under these conditions. The number of left-sided rotations increased, while the percentage of right-sided rotations decreased. The observed changes were accompanied by immune dysfunction. It was manifested in the depletion of lymphoid aggregates of the tracheal wall in lymphocytes and plasma cells. The severity of abnormal neurological symptoms and disturbances in immune homeostasis during the immediate stage of hemorrhagic stroke was greater in behaviorally passive rats than in active specimens.

Low-frequency fluctuation characteristics in rhesus macaques with SIV infection: a resting-state fMRI study.

Simian immunodeficiency virus (SIV)-infected macaque is a widely used model to study human immunodeficiency virus. The purpose of the study is to discover the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) changes in SIV-infected macaques. Seven rhesus macaques were involved in the longitudinal MRI scans: (1) baseline (healthy state); (2) SIV infection stage (12 weeks after SIV inoculation). ALFF and fALFF were subsequently computed and compared to ascertain the changes caused by SIV infection. Whole-brain correlation analysis was further used to explore the possible associations between ALFF/fALFF values and immune status parameters (CD4+ T cell counts, CD4/CD8 ratio and virus load). Compared with the baseline, macaques in SIV infection stage displayed strengthened ALFF values in left precuneus, postcentral gyrus, and temporal gyrus, and weakened ALFF values in orbital gyrus and inferior temporal gyrus. Meanwhile, increased fALFF values were found in left superior frontal gyrus, right precentral gyrus, and superior temporal gyrus, while decreased fALFF values existed in left hippocampus, left caudate, and right inferior frontal gyrus. Furthermore, ALFF and fALFF values in several brain regions showed significant relationships with CD4+ T cell counts, CD4/CD8 ratio, and plasma virus load. Our findings could promote the understanding of neuroAIDS caused by HIV infection, which may provide supplementary evidences for the future therapy study in SIV model.

Changes in Activity of Cysteine Cathepsins B and L in Brain Structures of Mice with Aggressive and Depressive-Like Behavior Formed under Conditions of Social Stress.

We studied activity of lysosomal cysteine proteases, cathepsins B and L, in brain structures (frontal cortex, caudate nucleus, hippocampus, and hypothalamus) of C57Bl/6J mice with aggressive and depressive-like behavior formed under conditions of chronic social stress (repeated experience of victories and defeats within 20 days). Mice with depressive-like behavior showed increased activity of cathepsin В in the hypothalamus and nucleus caudatus and increased activity of cathepsin L in the hippocampus compared to control animals not subjected to agonistic confrontations. In mice with aggressive behavior, protease activity in the studied brain structures was not changed. In 4 h after immune system activation with LPS (250 µg/kg), cathepsin L activity in the hippocampus of control mice increased in comparison with mice receiving saline. In contrast to control animals, LPS caused a decrease in activity of the enzyme in the caudate nucleus and frontal cortex of aggressive mice and in the hippocampus of mice with depressive-like behavior.

[Effects of repeated electroacupuncture on gene expression of cannabinoid receptor-1 and dopamine 1 receptor in nucleus accumbens-caudate nucleus region in inflammatory-pain rats].

OBJECTIVE: To observe the effect of repeated electroacupuncture (EA) on the expression of cannabinoid receptor-1 (CB 1) mrRNA and dopamine 1 receptor (D 1) mRNA in Nucleus Accumbens (NAC)-Caudate Nucleus (CN) region in inflammatory-pain rats, so as to study its underlying mechanism in analgesia. METHODS: A total of 30 SD rats were randomized into normal control, model, EA, EA+ AM 251 and WIN 55212-2 groups, with 6 cases in each group. EA (2 Hz/100 Hz, 1 -3 mA) was applied to "Zusanli"(ST 36) and "Kunlun"(BL 60) for 30 min, once every other day, and 4 sessions all together. Arthritis model was established by injection of Freund's complete adjuvant 0.05 mL in the rat's left ankle. Thermal pain threshold (paw withdrawal latency, PWL) was detected before and after modeling and after repeated EA and/or intraperitoneal injection of AM 251(an inverse antagonist at the CB 1 cannabinoid receptor, 0. 1 mg/100 g) and WIN 55212-2 (a potent cannabinoid receptor agonist, 0. 2 mg/100 g). The expression of CB 1 receptor mRNA and D 1 receptor mRNA in the NAC-CN region was measured by real time fluorescence quantitative-polymerase chain reaction. RESULTS: Compared with the control group, the pain threshold values of the model group was decreased significantly (P<0.01). In comparison with the model group, the pain threshold values of the EA group and WIN 55212-2 group were increased considerably on day 10 (P<0. 01). No significant differences were found between the EA+ AM 251 and model groups and between the EA and WIN 55212-2 groups in PWL after the treatment (P>0.05). Compared with the control group, both CB 1 R mRNA and D 1 R mRNA expression levels in the model group were increased slightly, while in comparison with the model group and EA+ AM 251 group, CB 1 R mRNA and D 1 R mRNA expression levels in the EA group and WIN 55212-2 group were upregulated obviously. No significant differences were found between the EA + AM 251 and model groups and between the EA and WIN 55212-2 groups in CB 1 R mRNA and D 1 R mRNA expression levels.

Antineuronal antibodies in OCD: comparisons in children with OCD-only, OCD+chronic tics and OCD+PANDAS.

Autoimmunity associated with a streptococcal infection has been proposed as a pathogenic mechanism for obsessive-compulsive disorder (OCD) in children. Antibrain antibody profiles were compared in children with OCD-only (n = 13; 14.1 +/- 3.1 years), OCD+PANDAS (n = 20; 11.3 +/- 1.5 years), OCD+Chronic Tic Disorder (n = 23; 13.4 +/- 3.5 years), and controls (n = 29; 12.4 +/- 2.4 years) using ELISA (orbitofrontal (OFC) and dorsolateral prefrontal cortex (DLPFC), caudate (CD), cingulate gyrus (CG)), immunoblotting (four regions plus putative antigens), and immunohistochemistry. ELISA and immunohistochemistry showed no differences among groups. Immunoblot showed that a greater percentage of individuals in the OCD+PANDAS cohort had reactive bands at 27 kDa (CD, CG, DLPFC), 36 kDa (CD), and 100 kDa (CD, OFC) and increased peak height at 67 kDa (all regions). Immunoblotting studies using the putative antigens (pyruvate kinase M1, aldolase C, alpha- and gamma-enolase) did not differ among groups. ASO titers were similar in all groups and did not correlate with immunoassays. It remains controversial whether childhood OCD is associated with autoimmune mechanisms.

Changes in hyporesponsiveness to acute amphetamine and age differences in tyrosine hydroxylase immunoreactivity in the brain over adolescence in male and female rats.

We investigated hyposensitivity after amphetamine in early (postnatal Day 30; P30) and late (P45) adolescent rats compared to adults (P70) in experiment 1. Locomotor activity was measured for 1 hr after the first (acute) and second (24 hr later) injection of amphetamine (0.5 or 1.5 mg/kg). P30 and P45 rats were transiently hypoactive compared to adults, as indicated by reduced locomotor activity after acute amphetamine and enhanced activity after the second injection in adolescents only. In experiment 2, ovariectomy did not alter locomotor activity during habituation at any age compared to intact rats, and, as for intact adolescents, ovariectomized adolescents continued to be less active after amphetamine than adults, suggesting gonadal immaturity alone cannot account for age differences in experiment 1. However, ovariectomy attenuated the increase in activity after the second treatment. In experiment 3 involving untreated rats, tyrosine hydroxylase immunoreactivity was reduced in P30, P40, and P50 compared to P90 rats in the nucleus accumbens core and the medial prefrontal cortex. Thus, adolescents may have an increased threshold of behavioral activation that can be overcome with either a higher dose or with repeated amphetamine treatment, and may be related to changes in the dopamine system over development.

Transplantation of rat neural stem cells reduces stereotypic behaviors in rats after intrastriatal microinfusion of Tourette syndrome sera.

Tourette syndrome (TS) is a heterogenous neuropsychiatric disorder. In most cases, tics are self-limited or can be treated by behavioral or pharmacological therapy. However, for some individuals, tics can cause lifelong impairment and life-threatening symptoms, which are intractable to traditional treatment. Neural stem cell (NSC) is a potential tool to treat certain neurological diseases. In this study, we proposed to use neural stem cell transplantation as a novel therapy to treat TS and discussed its efficacy. Wistar rats were microinfused with TS sera into the striatum followed by the transplantation of NSCs or vehicle at the infusion site. The sera of the TS patients were identified to have enriched antineural antibodies. Prior to grafting, rat embryonic NSCs were co-cultured with 5-bromodeoxyuridine (Brdu) for 24 h. Stereotypic behaviors were counted at 1, 7, 14 and 21 days after transplantation of NSCs. Morphological analyses revealed that NSCs survived and differentiated into neurons and astrocytes in the striatum 3 weeks after grafting. To sum it up, rat embryonic neural stem cell grafts survived and differentiated in the striatum of TS rat may help relieve stereotypic behaviors of the host. Our results suggest that transplantation of NSCs intrastriatum may have therapeutic potential for TS.

Effect of dopamine injection into caudate nucleus on immune responsiveness in rats: a pilot study.

Caudate nucleus (CN) plays a role in neural-immune interactions and dopamine is an important neurotransmitter in it. Hence, the effect of injection of dopamine and spiperone, a dopamine antagonist into the nucleus and lesion of caudate nucleus on humoral immunity was evaluated in albino rats. Dopamine injection into caudate nucleus at a dose of 4 microg/rat/day for 6 days was found to significantly attenuate antibody response following primary immunization of rats with sheep red blood cells (SRBC), decreased the spleen and body weight ratio and total globulin levels. Bilateral lesion of caudate nucleus also had similar effects whereas injection of spiperone (4 microg/rat/day for 6 days) into caudate nucleus enhanced the primary antibody response. The observed changes following dopamine or dopamine antagonist into caudate nucleus indicate that dopaminergic pathway of caudate nucleus negatively modulates humoral immunity in rats.

Regional changes of brain serotonin and its metabolite 5-hydroxyindolacetic Acid and development of immunosuppression in submissive mice.

The production of submissive behavior in C57BL/6J mice during 10 or 20 days of social confrontations resulted in increases in serotonin (5-HT) content in the amygdala, hippocampus, nucleus caudatus, Al1, A10, A9, and hypothalamus. The level of 5-hydroxyindolacetic acid (5-HIAA) was higher in most structures after 20 daily encounters compared to animals tested for 10 days. The ratio 5-HIAA/5-HT was increased in the nucleus raphe, accumbens, A9, and hypothalamus in mice displaying submission during 10 and 20 confrontations. The experience of defeats during 10 days accompanied with 5-HT system activation in a number of brain structures (nucleus raphe, accumbens, and A9) produced immunosuppression. With increasing number of confrontations the ratio 5-HIAA/5-HT was decreased in the same structures and a tendency to the immune response elevation appeared.

Prevalence of serum antibodies to caudate nucleus in autistic children.

Autism may involve autoimmunity to brain. We studied regional distribution of antibodies to rat caudate nucleus, cerebral cortex, cerebellum, brain stem and hippocampus. The study included 30 normal and 68 autistic children. Antibodies were assayed by immunoblotting. Autistic children, but not normal children, had antibodies to caudate nucleus (49% positive sera), cerebral cortex (18% positive sera) and cerebellum (9% positive sera). Brain stem and hippocampus were negative. Antibodies to caudate nucleus were directed towards three proteins having 160, 115 and 49 kD molecular weights. Since a significant number of autistic children had antibodies to caudate nucleus, we propose that an autoimmune reaction to this brain region may cause neurological impairments in autistic children. Thus, the caudate nucleus might be involved in the neurobiology of autism.

Ceruloplasmin immunoreactivity in neurodegenerative disorders.

Ceruloplasmin (CP) is a 132 kd cuproprotein which, together with transferrin, provides the majority of anti-oxidant capacity in serum. Increased iron deposition and lipid peroxidation in the basal ganglia of subjects with hereditary CP deficiency suggest that CP may serve as an anti-oxidant in the brain as well. The present study compared CP immunoreactivity in brain specimens from normal controls and subjects with neurodegenerative disorders (Alzheimer's disease [AD], Parkinson's disease [PD], progressive supranuclear palsy [PSP], and Huntington's disease [HD]) (n = 5 per group). The relative intensity of neuronal CP staining and the numbers of CP-stained neurons per 25x microscope field were determined in hippocampus (CA1, subiculum, and parahippocampal gyrus), parietal cortex, frontal cortex, substantia nigra, and caudate. CP was detected in both neurons and astrocytes in all specimens, and in senile plaques and occasional neurofibrillary tangles in AD brain. Neuronal CP staining intensity tended to increase in most AD brain regions, but was statistically significant vs controls only in the CA1 region of hippocampus (p = .016). Neuronal CP staining in brain specimens from other neurodegenerative disorders showed a slight but nonsignificant increase vs controls. The numbers of CP-stained neurons per field did not differ between the various neurodegenerative disorders and controls. These results suggest that a modest increase in neuronal CP content is present in the AD brain, and lesser elevations in neuronal CP occur in the other neurodegenerative disorders in this study. Though CP functions as both an acute phase protein and an anti-oxidant in peripheral tissues, whether it does so in the brain remains to be determined.

Antibodies against human putamen in adolescents with anorexia nervosa.

OBJECTIVE: To examine whether antiputamen antibodies are present in adolescents with anorexia nervosa (AN). METHOD: Using enzyme-linked immunosorbent assay (ELISA) with an extract of human putamen as an antigen, sera samples obtained from 22 adolescents with active AN and from 22 healthy adolescents (control group) were assayed for antibodies to neuronal components RESULTS: Mean optical density (OD) readings for serum antibodies against human putamen in adolescents with AN was significantly greater than the mean OD readings in the control group (0.492 +/- 0.086 vs. 0.275 +/- 0.028, p =.02). When serum positivity was defined as an OD level greater than 2 SD above the mean control group value (0.541), antiputamen antibodies were detected in the blood of 6 AN patients (27%) whereas they were detected in the blood of 1 patient (5%) in the control group (p <.05; Fisher's exact test). DISCUSSION: The detection of antiputamen antibodies in adolescents with AN suggests an underlying immune process at the putamen level in some patients with this eating disorder.

[Participation of the rat caudate nucleus in the immunostimulating effect of DAGO]. / Uchastie khvostatogo iadra krys v realizatsii immunostimuliruiushchego éffekta DAGO.

The data obtained suggest that administration of the DAGO increased the number of plaque- and rosette-forming cells after immunisation with the sheep red blood cells in the sham-operated Wistar rats. Following destruction of the caudate nucleus, the DAGO administration prevented the immune activation. Bilateral destruction of the caudate nucleus resulted in a considerable inhibition of the immune response as compared with the control rats. Thereupon the caudate nucleus seems to be involved in realisation of the DAGO-induced immune activation.

Inflammatory responses and their impact on beta-galactosidase transgene expression following adenovirus vector delivery to the primate caudate nucleus.

An E1, E3 deleted adenovirus vector, serotype 5, carrying the marker gene LacZ was bilaterally microinfused into the caudate nuclei of 10 St Kitts green monkeys. The location and number of cells expressing transgene and host immunologic response were evaluated at 1 week (n = 2) and 1 month (n = 8) following vector infusion. A large number of cells expressed beta-galactosidase in some monkeys, exceeding 600000 in one monkey, but no expression was seen in three of 10. All monkeys had positive adenoviral antibody titers before vector infusion, indicating the possibility of previous exposure to some adenovirus, but only one showed a significant increase in titer afterwards. Inflammatory cell markers revealed an inverse correlation between transgene expression and the extent of inflammatory response. Dexamethasone administered immediately before and for 8 days following vector delivery, however, had no effect on transgene expression. The demonstration of significant inflammatory responses in the brain of some individual primates, including demyelination, indicates the need for new generations of adenovirus vectors, or the successful suppression of inflammatory responses, before this vector is suitable for non-cytotoxic clinical applications in the CNS.

Restricted unilateral Sydenham's chorea: reversible contralateral striatal hypermetabolism demonstrated on single photon emission computed tomographic scanning.

Sydenham's chorea results from group A streptococcus infection and subsequent generation of antineuronal antibodies directed at the caudate nucleus and putamen. Predominantly bilateral, in up to 30% of cases the chorea can be unilaterally restricted. Imaging studies, both structural (magnetic resonance imaging) and functional (positron emission tomography), in patients with bilateral Sydenham's chorea have suggested reversible striatal abnormalities. Two patients with unilateral Sydenham's chorea are presented. Computed tomographic and magnetic resonance imaging were normal in both. However, hexamethylpropylenamine oxime single photon emission tomographic (HMPAO SPECT) studies demonstrated hypermetabolism in the contralateral basal ganglia. Resolution of symptoms in one of the patients coincided with normalization of the SPECT scan. Thus, unilateral striatal hypermetabolism appears to underlie the contralateral chorea observed. A SPECT scan probably should be included in the work-up of new-onset chorea.

Antineuronal antibodies in rheumatic chorea.

The objectives of our study were to examine the sera of rheumatic chorea (RhCh) patients (those with acute or chronic RhCh or with a past history of RhCh) for the presence of antineuronal antibodies (ANeurA) and to correlate the results with disease activity, chronicity, and the number and durations of choreic attacks. Subjects were inpatients of the Pediatric Hospital, Ain Shams University, and outpatients of the Outpatient Pediatric Cardiology Clinic (both in Cairo, Egypt). Forty children with RhCh (mean age, 10.9 years) and 40 healthy controls were tested. An indirect-immunofluorescence technique was used for the detection of ANeurA. ANeurA were present in the sera of 100, 93, and 44% of the patients with acute, chronic, and past histories of RhCh, respectively. A definition of chronic chorea is presented for the first time. None of the control subjects had ANeurA in their sera. The presence of ANeurA correlated with disease activity. A statistically significant increase (P < 0.01) in the prevalence of ANeurA was found for patients with active chorea (acute and chronic) compared with the prevalence in patients with past histories of RhCh (controlled chorea). ANeurA were present in the sera of both patients with acute RhCh and patients with chronic RhCh, yet patients with acute RhCh showed more brightness and cell staining than chronic patients. The severity, number, and duration of each attack were not related to the presence of ANeurA. These results strengthen further the concept of autoimmunity being the basis for the pathogenesis of RhCh. The presence of ANeurA correlated with the activity of RhCh but not with the severity, number, or duration of attacks. Humoral immunity definitely plays a role in RhCh; thus, routine administration of corticosteroids to patients with acute RhCh is suggested to prevent neuron damage and chronicity. The chronicity of chorea is not due to a further increase in ANeurA but is probably due to sensitivity to these antibodies.

Antineuronal antibodies: tics and obsessive-compulsive symptoms.

Fluorescent serum antibody determinations were used to examine whether children with obsessive-compulsive disorder (OCD) or less pervasive obsessive-compulsive symptoms (OCS) would show evidence of caudate nucleus involvement. Recent studies of OCD have documented smaller caudate nucleus volumes in adults with childhood onset than in normal controls, but not smaller putamen volumes. Thirty-eight cases were recruited from an ongoing study of childhood neurodevelopmental disorders. Nineteen samples from clinical cases had existing or previously documented OCS and attention-deficit hyperactivity disorder (ADHD) with or without concomitant tics. Nineteen additional clinical controls with ADHD, but without tics or OCS, were identified. The sera from clinical cases showed antibodies directed against caudate [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.0 to 4.1], putamen (OR 3.0; 95% CI 1.5 to 5.8), or both (OR 2.9; 95% CI 1.58 to 5.7) at a rate significantly higher than that of clinical controls, providing evidence of basal ganglia involvement in OCS. These preliminary data do not support a differential effect against caudate compared to putamen for these children, but suggest a more generalized central nervous system response.

[Serotonin antibodies and their possible role in parkinsonism]. / Antitela k serotoninu i ikh vozmozhnaia rol' pri parkinsonizme.

Serotonin antibodies (SAb) were found in the blood sera of middle-aged and elderly parkinsonian patients. The incidence of Sab in young and middle-aged healthy subjects was less, but increasing with age. Injected into the rabbit caudate nuclei, Sab suppressed the main pathogenetic mechanism of parkinsonian syndrome, the generator of pathologically enhanced excitation (GPEE) and parkinsonian symptoms induced by the MPP injection into substantia nigra. The intracaudate injection of serotonin enhanced GPEE activity and parkinsonian syndrome. The role of serotoninergic system and Sab in parkinsonism is discussed.

Amyotrophic choreo-acanthocytosis: a neuropathological and immunocytochemical study.

A 47 year old man, one of a sibship affected by amyotrophic choreo-acanthocytosis was studied neuropathologically after some years of clinical observation. Besides the classic optical findings (neuronal loss, astrocytic gliosis and "status spongiosus" in the basal ganglia, namely in the caudate nucleus) a few MEnk+ and NPY+ neurons were observed immunocytochemically in the striatum. In the spinal cord also, while no neuronal loss was perceivable, both mild demyelination and interfibrillary astrocytic hyperplasia of the long tracts were present. On the other hand, microscopic findings of muscle and peripheral nerve showed no differences from what was previously intra-vitam appreciated in the same patient. The neuropathological and immunocytochemical findings of this case are discussed in relation to the differential diagnosis between amyotrophic choreo-acanthocytosis and Huntington's disease.

Ovalbumin is more immunogenic when introduced into brain or cerebrospinal fluid than into extracerebral sites.

The magnitudes of serum antibody responses to ovalbumin have been compared following immunization via cerebral or extracerebral sites in Sprague-Dawley rats. In central nervous system (CNS)-immunized rats, conditions were designed to ensure normal brain barrier permeability. Extracerebral immunization was via the footpad or along pathways of antigen outflow from the CNS. The relative immunogenicity of different injection sites is: CSF greater than brain tissue greater than extracerebral sites. Enhancement of the antibody response to CNS-administered antigen appears to depend on events initiated within the CNS, since ovalbumin injected into blood (which reaches the spleen) or nasal submucosa (which drains to cervical nodes) fails to elicit a similar response.