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Biomedical subjects

B D Janković

Publications and source records attributed to B D Janković.

At least 19 recordsLinked to original sources
PubMed1995

Experimental allergic encephalomyelitis in adult DA rats subjected to neonatal handling or gentling.

The present study investigated the effect of daily handling and gentling between postnatal days 1 and 28 on experimental allergic encephalomyelitis (EAE) in 8-week old DA rats. Handling consisted of removing pups from the mother, and placing them in the novel cage for 15 min. The gentling procedure included handling accompanied by 3 min of dorsal tactile stimulation before returning the pups to the nest cage. Adult rats of both sexes handled in infancy showed increased susceptibility to EAE, as revealed by higher incidence of the disease, and more severe clinical signs. Anti-myelin basic protein (MBP) autoantibodies were increased in handled males, and decreased in handled females, compared to controls. Gentling induced aggravation of clinical signs and histopathological lesions of EAE in males, while in gentled females suppression was observed. These results indicated that both neonatal handling and gentling aggravated EAE induced in adult male rats. In female rats handling exacerbated, and gentling suppressed clinical EAE. The overall effect of neonatal manipulations was more pronounced in males. Furthermore, in mothers separated from their offspring due to handling and gentling, and immunized for EAE at day 28 postpartum, earlier appearance of clinical signs, and increased frequency of relapses compared to control dams was recorded.

Animals↗
PubMed1995

Maternal deprivation and early weaning modulate experimental allergic encephalomyelitis in the rat.

The present experiment deals with the effect of maternal deprivation (MD) and early weaning (EW) on the development and course of experimental allergic encephalomyelitis (EAE) in Dark August (DA) rats. Five litters (five to nine pups per liter) were subjected to MD (4 h daily) from Day 1 until Day 28. EW rats were weaned on Day 15 (EW-15, five litters) or Day 21 (EW-21, four litters). Control rats and MD rats were weaned on Day 28. At the age of 8 weeks, rats were immunized with guinea pig spinal cord in complete Freund's adjuvant and clinical signs of EAE were recorded daily. On Day 18 after immunization, rats were bled and sacrificed. Brain and spinal cord were examined histologically for EAE lesions. Serum anti-rat myelin basic protein (MBP) antibodies were detected by ELISA. MD female rats exhibited suppression of neurological and histological signs of EAE in comparison with control rats. MD and control females showed elevated anti-MBP antibody level compared to MD and control males. EW-15 female rats demonstrated potentiation of neurological signs of EAE compared to control females. EW-21 females developed more severe clinical signs and histological lesions compared to control females. These results show that neonatal experiences, such as maternal deprivation and early weaning, influence the development of EAE in adult DA rats.

Age Factors↗
PubMed1995

Opioid receptor-mediated suppression of humoral immune response in vivo and in vitro: involvement of kappa opioid receptors.

The selective kappa opioid receptor agonist MR 2034 exerted pronounced suppression of plaque-forming cell (PFC) response following intraperitoneal (i.p.) administration in the rat. Pretreatment with preferential kappa and mu opioid receptor antagonists MR 2266 and naloxone, respectively, revealed that this effect was mediated mainly by kappa, and to a low extent by mu opioid receptors. Intracerebroventricular (i.c.v.) administration of quaternary naltrexone (QNtx) moderately attenuated, whereas i.p. given QNtx completely prevented the suppressive effect of MR 2034, suggesting a peripheral mechanism of action, and only minor involvement of brain opioid receptors. MR 2034 markedly decreased the PFC response of spleen cells obtained from in vivo immunized rats, treated in vitro with the opiate. The immunosuppressive action of MR 2034 in vitro was completely and partially blocked by equimolar concentrations of MR 2266 and naloxone, respectively. Antagonists alone produced stimulation of PFC following i.p. administration in the rat, but did not affect PFC response upon in vitro treatment. These results suggest that peripheral kappa opioid receptors down-regulate primary humoral immune response in the rat, and that this effect may be produced by direct interference with plasma cell activity.

Animals↗
PubMed1995

Suppression of experimental allergic encephalomyelitis in offspring of DA and Wistar rats following immunization of mother with encephalitogen.

Immunization of female rats with encephalitogen before gestation, during gestation, and during lactation differentially decreased susceptibility to experimental allergic encephalomyelitis (EAE) in their offspring. The most pronounced suppression, revealed by lowered incidence and weaker clinical signs of the disease, was observed in offspring of mothers immunized before gestation and during lactation in both Dark August (EAE-susceptible), and Wistar (EAE-relatively resistant) rat strains. Induction of EAE in mothers during pregnancy only delayed the onset of the disease in DA progeny. The overall effect on EAE in offspring did not depend on the disease intensity in mothers. Our results suggest that anti-myelin basic protein (MBP) antibodies passively transferred from mothers are not responsible for the observed protection in offspring.

Animals↗
PubMed1994

Opposing activities of brain opioid receptors in the regulation of humoral and cell-mediated immune responses in the rat.

The role of brain delta- and kappa-opioid receptors in the regulation of PFC response, Arthus hypersensitivity reactions and delayed hypersensitivity reactions was studied following intracerebroventricular (i.c.v.) administration of opioid receptor agonists and antagonists. Eight-week-old male Wistar rats, with polyethylene cannulae inserted into the lateral brain ventricles, were i.c.v. treated with different doses of delta-opioid receptor agonist methionine-enkephalin (Met-Enk), delta-opioid receptor antagonist ICI 174864, kappa-opioid receptor agonist MR 2034, and kappa-opioid receptor antagonist MR 2266. In rats sensitized for plaque-forming cell (PFC) assay, the first drug injection was given 1 h prior to immunization, and then every 24 h until day 4. One h after the last treatment, rats were sacrificed and (PFC) assay performed. In rats immunized for hypersensitivity skin reactions, the first drug injection was given 1 h before immunization, and then every 48 h until day 14. Skin reactions were elicited one h after the last drug administration. Opioid receptor agonists Met-Enk and MR 2034 stimulated and suppressed PFC response, Arthus and delayed skin reactions respectively. ICI 174864 decreased the number of PFC and intensity of hypersensitivity skin reactions whereas MR 2266 increased the number of PFC, but did not affect to a greater extent hypersensitivity reactions. Stimulation of PFC produced by 1 microgram/kg of Met-Enk was completely blocked with 10 and 50 micrograms/kg of ICI 174864. MR 2034-induced suppression was partially and completely antagonized with 10 and 50 micrograms/kg of MR 2266 respectively. The present results suggest that brain opioid receptors differentially affect humoral and cell-mediated immune responses.

Analysis of Variance↗
PubMed1994

Behavioral and immunological events induced by electrical stimulation of the rat midbrain periaqueductal gray region.

We report here on the immunological and behavioral alterations induced by stimulation of the mesencephalic periaqueductal gray matter (PAG), a component of the brain aversive system. Male Wistar rats were implanted with stimulating electrodes in the caudal dorsolateral part of the PAG. After recovery, animals were screened for aversive behavior, characterized by running, jumping, vocalization or freezing reaction. Then, rats were subdivided to those which could control aversive stimulation (AS) by switch-off response (cAS group) and those which could not interrupt AS (uAS group). After sensitization with bovine serum albumin (BSA) in complete Freund's adjuvant, rats were stimulated 3 times/week for 40 days, each session lasting 30 min/rat. Immunological assessment included antibody production and hypersensitivity skin reactions to BSA 14 and 21 days after immunization. A behavioral profile of aversively stimulated animals was determined by a poststartle response, open field (OF) activity and two-way shuttle-box avoidance task. The results revealed elevated antibody production to BSA in cAS and lowered in uAS rats, compared to sham-stimulated and intact controls. Arthus and delayed hypersensitivity skin reactions increased in PAG-stimulated animals on day 14 but not on day 21 after immunization. Poststartle response was enhanced both in cAS and uAS rats. Along with immunopotentiation, administration of cAS produced hyperactivity in OF test and facilitation of the active avoidance learning, whereas uAS caused only moderate suppression of rearing in a novel OF environment. Physiological implications and possible mechanisms that may account for PAG-mediated immunobehavioral changes are outlined.

Animals↗
PubMed1994

Asymmetrical modulation of immune reactivity in left- and right-biased rats after ipsilateral ablation of the prefrontal, parietal and occipital brain neocortex.

We report here on the lateralized brain immunomodulation in male Wistar rats, a phenomenon related to the rotational bias of animal and the site of cortical lesion. Rats assigned to left- and right-rotators in a cylindrical Plexiglass rotometer were subjected to the ablation of the ipsilateral prefrontal cortex (PFC), parietal cortex (PC) and occipital cortex (OC) and sensitized with bovine serum albumin (BSA) in complete Freund's adjuvant. Intact and sham-lesioned left-biased animals demonstrated increased Arthus and delayed hypersensitivity skin reactions and antibody production to BSA in comparison with corresponding right-biased animals. PFC ablation decreased humoral and cellular immune responses to BSA in left- but increased in right-biased rats. Lesioning of PC decreased humoral immune reactions in left- but increased in right-rotating animals. OC ablation failed to produce immunological abnormalities. These results suggest that immunopotentiation is associated with the left neocortex, and immunosuppression with the right neocortex. The prefrontal cortex appears to be particularly associated with immune reactions.

Animals↗
PubMed1994

Neonatal sound stress and development of experimental allergic encephalomyelitis in Lewis and DA rats.

This experiment deals with the effect of neonatal sound stress on the susceptibility of rats in adult life to the induction of experimental allergic encephalomyelitis (EAE). Two inbred strains of rats, Lewis and DA, highly susceptible to EAE were used. On postnatal days 15, 18 and 21, animals of both sexes were sound stressed in a sound attenuated chamber (90dB, 60 rings/5 sec during 1 h, on a variable interval schedule) in the presence or absence of the mother. Experimental groups were as follows: (a) pups stressed without the mother (SP); (b) pups stressed in the presence of the mother (SPM); (c) control nonstressed pups separated from the mother (CP), and (d) control nonstressed pups undisturbed in their nest cages (CPM). Rats were weaned on postnatal day 28. At the age of 8 weeks, all groups were immunized with guinea pig spinal cord in complete Freund's adjuvant. Signs of EAE were recorded daily until the day 20 after immunization when animals were bled and sacrificed. Serial sections of cerebrum, cerebellum and spinal cord were examined histologically for the presence of mononuclear cell infiltrates. Anti-myelin basic protein (MBP) antibodies were detected in serum samples using ELISA technique. Stressed Lewis rats (groups SP and SPM) compared to control groups CP and CPM, developed more severe EAE as revealed by a higher aggregate clinical score, more pronounced histological lesions and increased production of anti-MBP antibodies. The presence of the mother during stress session (group SPM) prolonged the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of early experience on behavior and immune response in the rat.

The effect of maternal deprivation (MD) and preweaning handling on open field (OF) behavior, body and organ weights (spleen, thymus, and adrenals), and humoral immune response (plaque-forming cell response and antibody production) in adult male and female Wistar rats was studied. Maternal deprivation took place either for 28 postnatal days (2 h/day), or on days 15, 18, and 21 (2 h/day), whereas handling was performed daily during 28 postnatal days for 3 min. Sex differences were found both in behavior and immune response. The MD rats showed ambulatory hyperactivity in OF tests, females being more active than males, and a marked suppression of the PFC response. Handled rat's behavior was distinguishable from MD rats by an increased curiosity. Female handled rats were more active in the OF and their antibody production was higher. Male handled rats showed higher defecation scores and lower plaque-forming cell response. These results present evidence for a deprivation syndrome and immunosuppressive behavior in MD rats. Several mechanisms that may account for these immunobehavioral results are outlined.

Animals↗
PubMed1993

Locus ceruleus and immunity. I. Suppression of plaque-forming cell response and antibody production in rats with lesioned locus ceruleus.

Earlier research had demonstrated that lesions placed in different brain structures may alter the immune responsiveness. Norepinephrine is one of neurotransmitters which plays a role in immune reactions, and the locus ceruleus represents the largest group of norepinephrine-containing neurons in the brain. The present study concerns, therefore, the relationship between the locus ceruleus and humoral immune reactions. For this purpose, rats with electrolytically induced lesions in locus ceruleus were used in the study. Locus ceruleus-lesioned animals showed a decreased ability to produce hemolysin-releasing cells, hemagglutinins, and antibodies to bovine serum albumin. In brain-lesioned rats, thymus tended to the smaller in size, and there was a depletion of CD4+ helper/inducer lymphocyte population in the peripheral blood.

Agglutinins↗
PubMed1993

Locus ceruleus and immunity. II. Suppression of experimental allergic encephalomyelitis and hypersensitivity skin reactions in rats with lesioned locus ceruleus.

Rats with lesions restricted to the locus ceruleus were tested for immune inflammatory reactions. In these rats, Arthus and delayed skin hypersensitivity reactions to bovine serum albumin and old tuberculin were suppressed. The ablation of locus ceruleus completely inhibited the development of clinical signs of experimental allergic encephalomyelitis, markedly diminished the occurrence and intensity of lesions in the central nervous system, and significantly reduced the production of antibody against the rat brain myelin basic protein. These results establish a link between the locus ceruleus and immune inflammatory reactions in the rat.

Animals↗
PubMed1993

Brain-applied magnetic fields and immune response: role of the pineal gland.

In an attempt to clarify the mechanisms underlying immunopotentiation induced by prolonged exposure of the rat brain to static magnetic fields, and to evaluate the role of the pineal gland in that phenomenon, experiments were carried out on the following groups of adult rats (maintained under a 12 hr light/12 hr dark photoperiod): pinealectomized rats (Px); rats with micromagnets implanted to the occipito-parietal region of the skull (M); rats pinealectomized and implanted with micromagnets to the skull (PxM); sham-pinealectomized rats with non-magnetic beads implanted to the occipito-parietal area of the skull (ShPxMx); and intact controls (IC). Twenty-one days after surgery, animals of all groups were immunized with sheep red blood cells and tested for plaque forming cell (PFC) response and serum hemagglutinin level. Humoral immune reactions decreased significantly in Px rats, while increased markedly in M rats in comparison to the ShPxMx and IC controls. Compromised immune function induced by pinealectomy was restored by prolonged exposure of the brain to magnetic fields (PxM rats). Thus reconstituted immune responsiveness in PxM rats reached the level observed in controls, but was lower than that in M rats. The results imply that magnetic fields applied to the rat brain may exert their immunoenhancing activity in the absence of the pineal gland. However, this activity of magnetic fields is more pronounced in the presence of the pineal organ. The latter finding suggests the involvement of the pineal in the immunopotentiation induced by magnetic fields, but does not imply that magnetic fields operate solely via the pineal gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗