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Biomedical subjects

E M Sternberg

Publications and source records attributed to E M Sternberg.

At least 55 records · Page 3Linked to original sources
PubMed1994

The effect of chronic imipramine administration on the densities of 5-HT1A and 5-HT2 receptors and the abundances of 5-HT receptor and transporter mRNA in the cortex, hippocampus and dorsal raphe of three strains of rat.

We have recently demonstrated that the LEW/N rat contains lower concentrations of cortical and hippocampal 5-HT1A receptors compared with the F344/N and out-bred HSD rats. To further characterize these strains, we investigated the effect of chronic (8 wk) imipramine administration (5 mg/kg/day) on 5-HT1A and 5-HT2 receptor densities and mRNA in the cortex and hippocampus and 5-HT transporter mRNA in the dorsal raphe of LEW/N, HSD, and F344/N rats, using quantitative autoradiography and in situ hybridization histochemistry. After imipramine treatment, a significant increase in the levels of hippocampal 5-HT1A receptors, but not mRNA, was observed in LEW/N rats while the abundance of hippocampal 5-HT1A receptor mRNA, but not 5-HT1A receptor densities, decreased in F344/N rats. Cortical and hippocampal 5-HT2 receptor densities, but not mRNA, significantly decreased after imipramine administration in all three strains. Finally, 5-HT1A receptor densities and the abundance of mRNAs encoding the 5-HT1A receptor and 5-HT transporter in the dorsal raphe remained unaltered after imipramine administration in all three strains. The effects of imipramine on the levels of cortical and hippocampal 5-HT1A and 5-HT2 receptors and their transcripts, therefore, appear to be strain-dependent. The implications of these findings are discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia.

OBJECTIVE: To examine basal and stimulated hypothalamic-pituitary-adrenal (HPA) axis and related hormone levels, including adrenocorticotropin (ACTH), cortisol, arginine vasopressin (AVP), and neuropeptide Y (NPY), in patients with fibromyalgia (FM). METHODS: Basal and ovine corticotropin-releasing hormone (oCRH)-stimulated HPA axis function were assessed in 12 patients with FM and in age- and sex-matched normal subjects. Basal plasma AVP levels and AVP release after postural change were assessed, and plasma NPY levels were measured in the same samples. RESULTS: Patients with FM had low 24-hour urinary free cortisol, but normal peak and elevated trough plasma cortisol levels, compared with normal subjects. The net integrated ACTH response to oCRH in FM was not significantly different from that in normal subjects, but tended toward an exaggerated response. There was a significant decrease in net integrated cortisol response to oCRH in FM patients, indicating adrenal hyporesponsiveness. AVP levels were not significantly different between FM patients and control subjects, but variability was greater among the FM patients. Plasma NPY levels were significantly lower in FM patients than in normal subjects. CONCLUSION: These data support the view that HPA axis function is perturbed in patients with FM. Further study is required to ascertain the cause of HPA axis perturbations and their relationship to symptoms in patients with FM.

Adrenocorticotropic Hormone↗
PubMed1994

The role of the hypothalamic-pituitary-adrenal axis in susceptibility to autoimmune/inflammatory disease.

The central nervous system (CNS) affects the immune system through endocrine, paracrine, and neuronal mechanisms. The immune system in turn communicates with the CNS through many of the same mechanisms. Evidence that this bidirectional communication plays a vital role in susceptibility to inflammatory and infectious disease is derived largely from animal models in which the communication has been interrupted or reconstituted surgically, pharmacologically, or on a preexisting genetic basis. The advantage of animal models for studying the pathophysiologic relevance of such connections is that the systems can be manipulated at several levels and at different times in relation to development of the inflammatory disease and the outcome of the manipulation can be quantified. While in vitro studies may be used to further define the subcellular and molecular mechanisms of these interactions, only an intact organism, in which the central nervous system is connected to the immune system, can be used to fully define the nature of these interconnections. This review describes approaches to studying CNS-immune system interactions, using relatively inflammatory-susceptible and inflammatory-resistant Lewis and Fischer rats as models for evaluating the role of the HPA axis in susceptibility to inflammatory disease.

Animals↗
PubMed1994

Imipramine reduces the local inflammatory response to carrageenin.

Imipramine was administered chronically to LEW/N, outbred and F344/N rats which were then exposed to the aseptic irritant carrageenin in order to determine whether the decreased hypothalamic expression of CRH m-RNA previously shown to be associated with imipramine affects peripheral immune processes. Both LEW/N and outbred but not F344/N rats had vigorous inflammatory responses to carrageenin, and imipramine was associated with significant decreases in the local cellular inflammatory response to carrageenin. Imipramine was also associated with changes in the expression of peripheral blood cell MHC class II expression in LEW/N and outbred rats. These results suggest that at doses comparable to those used clinically imipramine has significant effects on response to an inflammatory stimulus.

Animals↗
PubMed1994

Differential mineralocorticoid (type 1) and glucocorticoid (type 2) receptor expression in Lewis and Fischer rats.

Lewis (LEW/N) and Fischer (F344/N) rats represent two extremes of the spectrum of corticosterone responses to stressful stimuli, from the chronical hyporesponsiveness of LEW/N to the chronical hyperresponsiveness of F344/N. It might be expected that the amount of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) binding, and the levels of their corresponding mRNAs in various tissues in LEW/N and F344/N rats might reflect the overall integrated levels of corticosterone to which these receptors have been exposed. We have found that while the binding affinity (Kd) of MR and GR varies between tissues, there was no strain difference in any tissue. Receptor binding number (Bmax), however, varied not only between tissues, but also between strains. MR Bmax in the hippocampus and pituitary was lower in LEW/N than in F344/N, whereas the GR Bmax in the LEW/N thymus was greater than that found in F344/N rats. The hippocampal levels of MR mRNAs in Adx LEW/N and F344/N rats were in good agreement with, and paralleled, the functional levels of these receptors as determined by binding assays. On the other hand, the number of hippocampal GR binding sites and the level of GR nRNA while similar were not identical in the two strains: the hippocampal GR Bmax did not differ between strains, while the hippocampal GR mRNA level was slightly, but significantly, lower in Adx LEW/N compared to F344/N rats.

Aldosterone↗
PubMed1994

Multiple sclerosis is associated with alterations in hypothalamic-pituitary-adrenal axis function.

In the LEW/N rat model, a decreased hypothalamic-pituitary-adrenal (HPA) axis response to inflammatory and immune mediators confers susceptibility to the development of a variety of inflammatory and immune diseases, including experimental allergic encephalomyelitis. In humans with optic neuritis, early intervention with steroids is associated with a decrease in the number of patients who go on to develop multiple sclerosis (MS). The current study was designed to determine whether patients with MS show evidence of a hypoactive HPA axis. Thirteen patients with MS were studied at baseline and with provocative tests of HPA axis function [ovine CRH, arginine vasopressin (AVP), and ACTH stimulation]. Compared to matched controls, patients with MS had significantly higher plasma cortisol levels at baseline. Despite this hypercortisolism and in contrast to patients with depression who had similar elevations in plasma cortisol levels, patients with MS showed normal, rather than blunted, plasma ACTH responses to ovine CRH, suggesting that the pathophysiology of hypercortisolism in MS is different from that in depression. Patients with MS also showed blunted ACTH responses to AVP stimulation and normal cortisol responses to high and low dose ACTH stimulation. Taken together, these findings are compatible with data from studies of experimental animals exposed to chronic inflammatory stress, which showed mild increased activation of the HPA axis with increased relative activity of AVP in the regulation of the pituitary-adrenal axis. These data do not support a role for hypocortisolism in MS once the disease is established.

Adrenal Glands↗
PubMed1994

The stress response in critical illness.

Under normal, unstressed conditions, the body maintains a dynamic equilibrium known as homeostasis--a complex interplay balancing the conflicting demands presented by many internal and external forces. In the face of threatened or actual disruptions (i.e., stress), molecular, cellular, physiologic, and behavioral responses act to restore homeostasis. These responses can be specific to a particular stressor and relatively circumscribed (e.g., secretion of insulin in response to an increase in blood glucose), or can be generalized and relatively nonspecific (e.g., behavioral manifestations of severe anxiety). Typically, more nonspecific and generalized responses occur in the setting of severe and threatening disruptions in homeostasis, and taken together, these responses are known as the "general adaptation or stress syndrome". We will describe the elements and organization of the generalized stress response with particular attention to the hypothalamic-pituitary-adrenal axis as it interacts with the immune system, and we will review what is known about this interactive network in the setting of critical illness.

Animals↗
PubMed1993

Release of hypothalamic corticotropin-releasing hormone and arginine-vasopressin by interleukin 1 beta and alpha MSH: studies in rats with different susceptibility to inflammatory disease.

The susceptibility of Lewis rats is related to blunted hypothalamic-pituitary-adrenal (HPA) axis responsiveness to a variety of inflammatory and neuroendocrine stimuli. In contrast resistance to inflammatory disease of histocompatible Fischer rats is associated with their intact HPA axis responses to the same stimuli. We have examined the contribution of IL-1 beta to in vitro corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) release from hypothalamic explants derived from LEW/N and F344/N rats. The same animal model has been used to investigate the regulatory effect of alpha MSH, an immunosuppressive neurohormone, on IL-1 beta stimulated CRH and AVP secretion. CRH basal release in both strains was similar. However, LEW/N hypothalamic AVP basal secretion was significantly elevated. CRH relative response of LEW/N hypothalamic explants to IL-1 beta stimulation was lower compared to Fischer, which is consistent with their hyporesponsiveness to inflammatory mediators. AVP secretion however, was significantly decreased in hypothalamic explants from both strains after 40 min exposure to IL-1 beta. alpha MSH suppressed basal CRH and AVP release in both LEW/N and F344/N rats and prevented IL-1 beta stimulated CRH secretion in these strains. AVP was further diminished in F344/N explants following incubation with alpha MSH + IL-1 beta, while LEW/N level was significantly elevated. However, AVP levels remained significantly below baseline in explants from both strains after final incubation with IL-1 beta. Although our findings indicate a modulatory action of alpha MSH in HPA axis regulation in vitro, the physiological importance of this phenomenon in Lewis and Fischer rats requires further investigation.

Animals↗
PubMed1993

Role of CRH in glucopenia-induced adrenomedullary activation in rats.

Acute glucoprivation profoundly stimulated hypothalamic-pituitary-adrenocortical (HPA) and adrenomedullary outflows. Whether these responses reflect a single central mechanism regulated by corticotropin-releasing hormone (CRH) has been unclear. This study examined the role of endogenous CRH in HPA and adrenomedullary responses to hypoglycemia in Sprague-Dawley rats, by using anti-CRH immune serum or a CRH antagonist (alpha-helical h/r CRH9-41, and in Lewis rats, a strain characterized by deficient hypothalamic CRH responses during stress. In conscious Sprague-Dawley rats with indwelling arterial and venous cannulas, insulin (0.3 U/kg was injected iv, and responses of serum glucose concentrations and plasma levels of corticotropin (ACTH) and catechols (including epinephrine, EPI; norepinephrine, NE; dihydroxyphenylalanine, DOPA; dihydroxyphenylglycol, DHPG; and dihydroxyphenylacetic acid, DOPAC) were assessed, with or without pretreatment with anti-CRH immune serum (0.5 or 1.0 ml iv or 10 microl icv) or alpha-helical h/r CRH9-41 (130 nmol iv or 13 nmol icv). Responses to insulin (1.0 U/kg iv) were also measured in conscious juvenile Lewis and Fischer 344/N rats. Insulin-induced hypoglycemia markedly increased plasma levels of EPI and ACTH in all groups. Pretreatment iv with 1/0 ml of anti-CRH immune serum blocked the ACTH response to insulin but failed to attenuate the EPI response. alpha-helical h/r CRH9-41, whether given iv or icv, failed to alter ACTH or EPI responses to insulin, although the antagonist did block EPI responses to icv CRH. Hypoglycemia elicited similar increments in ACTH levels in Lewis rats and Fischer 344/N control rats; and although Lewis rats had lower baseline EPI and smaller responses of NE, DHPG, DOPA, and DOPAC levels, the groups did not differ in proportionate increments in EPI levels. The results indicate that the ACTH response to hypoglycemia depends on availability of CRH outside the blood-brain barrier--presumably in the pituitary gland. The findings with icv alpha-helical h/r CRH9-41 can be explained by failure of the antagonist to reach effective concentrations at central sites of action of endogenous CRH, or by mechanisms other than CRH release determining the adrenomedullary response to hypoglycemia. Lewis rats seem to have less adrenomedullary secretion at baseline and smaller responses of NE synthesis and release during hypoglycemia than do Fischer 344/N rats. Neurochemical evidence for differential adrenomedullary and sympathoneural responses during hypoglycemia in all three rat strains is inconsistent with Cannon's view of a functionally unitary sympathoadrenal system. Lewis rats have deficient CRH responses to some stressors but not to others, or else pituitary-adrenomedullary responses in this setting depend on mechanisms other than CRH release in the brain. Both explanations are inconsistent with the doctrine of non-specificity, the main tenet of Selye's stress theory.

Adrenal Medulla↗
PubMed1993

A decomposition product of a contaminant implicated in L-tryptophan eosinophilia myalgia syndrome affects spinal cord neuronal cell death and survival through stereospecific, maturation and partly interleukin-1-dependent mechanisms.

The L-tryptophan eosinophilia myalgia syndrome (L-TRP-EMS), an inflammatory syndrome characterized by eosinophilia, myalgias, perimyositis, fasciitis and neuropathies, occurred in epidemic proportions in the United States in the summer and fall of 1989. The neuropathic clinical features in L-TRP EMS are complex and mixed. In the present study, one of the impurities most highly associated with development of L-TRP EMS, 1,1'-ethylidenebis[L-tryptophan] (EBT), and two of its diastereoisomeric breakdown products, were compared for evidence of neurotoxicity in vitro. In 1-month-old spinal cord cultures derived from fetal mice, synthetic (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (1S-beta-C) produced a 30 to 35% loss in numbers of neurons. Toxicity was not apparent after treatment with the R-isomer of the same compound or with the parent compound, EBT. Cotreatment of cultures with 1S-beta-C and neutralizing antiserum to interleukin-1 alpha (IL-1 alpha), or with 1S-beta-C and neutralizing antiserum against the murine IL-1 receptor, prevented neuronal cell death associated with 1S-beta-C. Recombinant IL-1 alpha also produced neuronal killing that was not additive to that observed with the 1S-beta-C treatment. In contrast, in immature spinal cord neuronal cultures, the 1S-beta-C, but not the 1R-beta-C or EBT, prevented the 30% cell death which normally occurs in these cultures. Neither neutralizing anti-IL-1 antibody, nor anti-IL-1 receptor antibody blocked the neuronal survival effect, suggesting that 1S-beta-C induces neuronal survival through a receptor-mediated mechanism independent of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The stress response and the regulation of inflammatory disease.

The molecular and biochemical bases for interactions between the immune and central nervous systems are described. Immune cytokines not only activate immune function but also recruit central stress-responsive neurotransmitter systems in the modulation of the immune response and in the activation of behaviors that may be adaptive during injury or inflammation. Peripherally generated cytokines, such as interleukin-1, signal hypothalamic corticotropin-releasing hormone (CRH) neurons to activate pituitary-adrenal counter-regulation of inflammation through the potent antiinflammatory effects of glucocorticoids. Corticotropin-releasing hormone not only activates the pituitary-adrenal axis but also sets in motion a coordinated series of behavioral and physiologic responses, suggesting that the central nervous system may coordinate both behavioral and immunologic adaptation during stressful situations. The pathophysiologic perturbation of this feedback loop, through various mechanisms, results in the development of inflammatory syndromes, such as rheumatoid arthritis, and behavioral syndromes, such as depression. Thus, diseases characterized by both inflammatory and emotional disturbances may derive from common alterations in specific central nervous system pathways (for example, the CRH system). In addition, disruptions of this communication by genetic, infectious, toxic, or pharmacologic means can influence the susceptibility to disorders associated with both behavioral and inflammatory components and potentially alter their natural history. These concepts suggest that neuropharmacologic agents that stimulate hypothalamic CRH might potentially be adjunctive therapy for illnesses traditionally viewed as inflammatory or autoimmune.

General Adaptation Syndrome↗
PubMed1992

Repeated coronary artery spasm in a young woman with the eosinophilia-myalgia syndrome.

We report a case of repeated coronary artery spasm with myocardial injury in a 37-year-old woman with the eosinophilia-myalgia syndrome. This patient did not have a medical history of cardiac-related illness or risk factors for coronary artery disease. The presence of eosinophil granule major basic protein in otherwise normal-appearing myocardial tissue, along with normal plasma levels of tryptophan metabolites, suggests that the mechanism of vasospasm in this patient might involve toxic eosinophil proteins or focal myocardial lesions, but not the production of excess tryptophan metabolites.

Adult↗
PubMed1992

Corticotropin releasing hormone related behavioral and neuroendocrine responses to stress in Lewis and Fischer rats.

We have recently shown that susceptibility to streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats is related to a lack of glucocorticoid restraint of inflammation while the relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats is related to their greater hypothalamic-pituitary-adrenal (HPA) axis response. The difference in pituitary-adrenal responsiveness results from decreased inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion in LEW/N rats. Because CRH not only activates the pituitary-adrenal axis, but also is associated with behavioral responses that are adaptive during stressful situations, we wished to determine if the differential LEW/N and F344/N CRH responsiveness to inflammatory mediators could also be associated with differences in neuroendocrine and behavioral responses to physical and emotional stressors. In this study, LEW/N rats exhibited significant differences compared to F344/N rats, in plasma adrenocorticotropin hormone (ACTH) and corticosterone responses during exposure to an open field, swim stress, restraint or ether. Furthermore, hypothalamic paraventricular CRH mRNA expression was also significantly lower in LEW/N compared to F344/N rats after restraint. These differences in neuroendocrine responses were associated with differences in behavioral responses in LEW/N compared to F344/N rats in the open field. Outbred HSD rats, which have intermediate and overlapping arthritis susceptibility compared to LEW/N and F344/N rats, exhibited intermediate and overlapping plasma corticosterone and behavioral responses to stressful stimuli compared to the two inbred strains. These data suggest that the differences in CRH responses in these strains may contribute to the behavioral and neuroendocrine differences we have observed. Therefore these strains may provide a useful animal model for studying the relationship between behavior, neuroendocrine and inflammatory responses.

Adrenocorticotropic Hormone↗
PubMed1992

Arthritis-susceptible Lewis rats fail to emerge from the stress hyporesponsive period.

Susceptibility to streptococcal cell wall (SCW)-induced arthritis in 4- to 6-week-old Lewis (LEW/N) rats is associated with blunted glucocorticoid production secondary to a profound defect in inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion. The relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats, on the other hand, is associated with robust hypothalamic-pituitary-adrenal (HPA) axis responses to inflammatory mediators. In this study, we investigated HPA axis responses to SCW during the postnatal developmental period in LEW/N and F344/N rats. We found that SCW-induced plasma corticosterone (CORT) responses do not significantly increase during development in LEW/N, while such responses clearly appear at postnatal day 14 in F344/N and outbred Harlan-Sprague-Dawley (HSD) rats. Additionally, LEW/N rats fail to exhibit the normal ontogenic increase in CRH mRNA levels in the paraventricular nucleus (PVN), whereas their SCW-induced PVN CRH mRNA responses are blunted compared to F344/N at postnatal day 14. Taken together, these results suggest that LEW/N rats fail to emerge completely from their stress hyporesponsive period. This may account for the lack of stress responsiveness in young adult LEW/N rats, and consequently, for their susceptibility to SCW-induced arthritis and other inflammatory diseases.

Animals↗
PubMed1992

Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats.

We have previously demonstrated that susceptibility of Lewis (LEW/N) rats to inflammatory disease, compared to relatively resistant Fischer (F344/N) rats, is related to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone (CRH) responsiveness to inflammatory and other stress mediators. The GABA/benzodiazepine receptor complex is an important negative modulator of CRH secretion and responsiveness to excitatory stimuli. In this study, we have examined in vitro binding of [3H]flunitrazepam to hypothalamic membrane preparations from LEW/N and F344/N rats. LEW/N rats had significantly more hypothalamic benzodiazepine binding sites (Bmax) than F344/N rats, but there were no differences in benzodiazepine binding affinities (Kd) between these two strains. The differences in benzodiazepine receptor number were consistent with the respective plasma corticosterone levels in the two strains, and with previous work indicating a negative correlation between corticosterone levels and benzodiazepine binding site number. Adrenalectomy of F344/N rats increased benzodiazepine binding to levels comparable to LEW/N animals and treatment of adrenalectomized F344/N rats with DEX resulted in lowering of benzodiazepine Bmax to levels that did not differ significantly from those of intact F344/N rats. There was no significant change in receptor number in either adrenalectomized or DEX-treated LEW/N rats. These findings suggest that basal benzodiazepine receptor differences between these strains may be partially related to strain differences in corticosterone levels, however that additional factors may contribute to maintenance of these differences in LEW/N rats. Since benzodiazepines attenuate hypothalamic CRH secretion through GABAergic inhibition, we suggest that strain differences in receptor number could also augment strain differences in hypothalamic-pituitary-adrenal axis function through differential sensitivity to GABA-mediated feedback.

Adrenalectomy↗
PubMed1992

Tryptophan metabolism via the kynurenine pathway in patients with the eosinophilia-myalgia syndrome.

OBJECTIVE: To investigate the metabolism of L-tryptophan (LT) via the kynurenine pathway in patients with the eosinophilia-myalgia syndrome (EMS). METHODS: Measurement of LT, L-kynurenine, and quinolinic acid in plasma and cerebrospinal fluid (CSF) from subjects with EMS, from asymptomatic users of LT, and from normal subjects. RESULTS: Plasma LT concentrations were lower in untreated EMS patients (n = 5) than in corticosteroid-treated EMS patients (n = 5; P less than 0.05) and in asymptomatic users of LT (n = 5; P less than 0.05). Untreated EMS patients, who had discontinued LT weeks to months prior to study, had significantly higher plasma levels of L-kynurenine and quinolinic acid than did corticosteroid-treated EMS patients (P less than 0.05), normal subjects (P less than 0.02), and asymptomatic users of LT (P less than 0.05). EMS patients also had significantly elevated levels of L-kynurenine (P less than 0.05) and quinolinic acid (P less than 0.001) in CSF compared with normal subjects. After a 1-gm oral dose of LT, untreated EMS patients (n = 4) showed lower peak levels of LT and accentuated synthesis of L-kynurenine and quinolinic acid, compared with these values in corticosteroid-treated EMS patients (n = 2), who responded like normal subjects (n = 5). CONCLUSION: These data demonstrate that during the active phase of EMS, LT metabolism via the kynurenine pathway was accentuated, probably secondary to induction of the enzyme indoleamine-2,3-dioxygenase. Ingestion of large amounts of LT (median daily dose 1.5 gm) resulted in high concentrations of kynurenine-pathway metabolites in blood and extrahepatic tissues, which was accentuated in EMS patients and which may have played a significant role in the pathogenesis of the disease.

Adrenal Cortex Hormones↗
PubMed1992

Differential behavioral response in LEW/N and F344/N rats: effects of corticotropin releasing hormone.

1. Previous studies have documented that LEW/N rats exhibit an inflammatory response when challenged with a variety of stressful stimuli while histocompatible F344/N rats do not. These differences are thought to be regulated by the HPA axis. 2. In order to examine behavioral correlates of suspected differences in HPA activity in these strains, the baseline response to an open field as well as the effects of 3 micrograms/rat of CRH i.c.v. were compared across strains. 3. Significant differences in the pattern of activity in the open field, rearing, and grooming, as well as effects of CRH were found between strains. 4. The differences found are consistent with the notion that differences in endogenous CRH may form the basis for the differential susceptibility of these strains to autoimmune disease, and provide a model to study genetic determinants of CNS-immune system interactions.

Animals↗