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The most advantageous combination of immunosuppressive agents for cardiac transplant recipients has not yet been established. Between November 2001 and June 2003, 343 de novo cardiac transplant recipients were randomized to receive steroids and either tacrolimus (TAC) + sirolimus (SRL), TAC + mycophenolate mofetil (MMF) or cyclosporine (CYA) + MMF. Antilymphocyte induction therapy was allowed for up to 5 days. The primary endpoint of ≥3A rejection or hemodynamic compromise rejection requiring treatment showed no significant difference at 6 months (TAC/MMF 22.4%, TAC/SRL 24.3%, CYA/MMF 31.6%, p = 0.271) and 1 year (p = 0.056), but it was significantly lower in the TAC/MMF group when compared only to the CYA/MMF group at 1 year (23.4% vs. 36.8%; p = 0.029). Differences in the incidence of any treated rejection were significant (TAC/SRL = 35%, TAC/MMF = 42%, CYA/MMF = 59%; p < 0.001), as were median levels of serum creatinine (TAC/SRL = 1.5 mg/dL, TAC/MMF = 1.3 mg/dL, CYA/MMF = 1.5 mg/dL; p = 0.032) and triglycerides (TAC/SRL = 162 mg/dL, TAC/MMF = 126 mg/dL, CYA/MMF = 154 mg/dL; p = 0.028). The TAC/SRL group encountered fewer viral infections but more fungal infections and impaired wound healing. These secondary endpoints suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients, including fewer ≥3A rejections or hemodynamic compromise rejections and an improved side-effect profile.

Background: Chronic renal allograft failure (CRAF) is the leading cause of graft loss post-renal transplantation. This study evaluated the efficacy and safety of tacrolimus as secondary intervention in cyclosporine-treated kidney transplantation patients with impaired allograft function as indicated by elevated serum creatinine (SCr) levels. Methods: Patients receiving cyclosporine-based immunosuppression who had an elevated SCr at least 3 months post-renal transplantation were enrolled. Treatment allocation was 2:1 to switch to tacrolimus or continue cyclosporine. This analysis was performed after 2 yr; patients will be followed for an additional 3 yr. Results: There were 186 enrolled and evaluable patients. On baseline biopsy, 90% of patients had chronic allograft nephropathy. Baseline median SCr was 2.5 mg/dL in both treatment groups. For patients with graft function at month 24, SCr had decreased to 2.3 mg/dL in the tacrolimus-treated patients and increased to 2.6 mg/dL in the cyclosporine-treated patients (p = 0.01). Acute rejection occurred in 4.8% of tacrolimus-treated patients and 5.0% of cyclosporine-treated patients during follow-up. Two-year allograft survival was comparable between groups (tacrolimus 69%, cyclosporine 67%; p = 0.70). Tacrolimus-treated patients had significantly lower cholesterol and low-density lipoprotein levels and also had fewer new-onset infections. Cardiac conditions developed in significantly fewer tacrolimus-treated patients (5.6%) than cyclosporine-treated patients (24.3%; p = 0.004). Glucose levels and the incidences of new-onset diabetes and new-onset hyperglycemia did not differ between treatment groups. Conclusions: Conversion from cyclosporine to tacrolimus results in improved renal function and lipid profiles, and significantly fewer cardiovascular events with no differences in the incidence of acute rejection or new-onset hyperglycemia.

Two previous studies from our laboratory have indicated that the ventral glial limitans subjacent to the hypothalamic supraoptic nucleus (SON-VGL) undergoes a reversible thinning upon chronic activation of the magnocellular neuroendocrine cells (MNCs) of the supraoptic nucleus (SON). Numerous other studies have shown that MNC somata hypertrophy with activation. One aim of the current study was to understand better how SON-VGL thinning occurs. A second aim was to quantify overall changes of the MNC somata region due to cellular hypertrophy to compare relative changes in dimensions. Here, we undertook a light microscopic stereological investigation of the SON and the subjacent SON-VGL of Nissl stained material under basal and activated conditions. Astrocyte numbers in the underlying SON-VGL remained stable across hydration state as did the overall volume of the SON-VGL and dendritic zone reference area. How these data are consistent with our earlier observations of SON-VGL thinning was resolved by the finding of a highly significant, 30% increase in the mediolateral dimension of the SON-VGL in dehydrated rats. These observations fit well with previous work from our laboratory that demonstrates a reorientation of SON-VGL astrocytes, from vertical to horizontal, which occurs in the activated SON-VGL. We found a significant, approximately 54%, increase in the overall volume of the MNC region of the SON. No significant rostrocaudal lengthening of the SON was detected, although a trend was evident. All the observed changes reversed with rehydration. These data indicate that elasticity of the SON-VGL acts to accommodate the volume expansion of the MNCs and enables the SON-VGL to continue as an interface between the underlying cerebrospinal fluid in the subarachnoid space and the expanded SON above.

Background. A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years. Methods. Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. Results. The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P =0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. Conclusions. All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Background Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation. Methods A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year. Results There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups. Conclusions All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.

Cultured astroglia express purinergic receptors that initiate phosphoinositide metabolism and calcium mobilization. Experiments were conducted to characterize the purinergic receptor subtype on type 1 astroglia responsible for stimulation these second-messenger systems. Inositol phosphate (IP) accumulation and calcium mobilization were measured after stimulation with ATP or purinergic receptor subtype-selective ATP analogues. ATP (10(-5) M) increased IP accumulation severalfold. Dose-effect assays monitoring astroglial IP accumulation revealed the order of potency that defines the P2Y receptor: 2-methylthioadenosine 5'-triphosphate greater than ATP greater than alpha beta-methyleneadenosine 5'-triphosphate greater than beta gamma-methyleneadenosine 5'-triphosphate. The influence of ATP on intracellular calcium levels in individual type 1 astroglia was examined using the calcium indicator dye, fura-2. Dose-effect experiments indicated that ATP was equally potent for generating inositol phosphates and increasing cellular calcium. The most prevalent response (87% of total responses) to ATP consisted of a rapid increase in calcium to a peak level that was approximately five times greater than the prestimulation level. This peak was followed by a decline to a plateau level that was significantly above baseline. This plateau phase of the calcium increase was maintained for at least 5 min in the presence of ATP and was dependent on external calcium. Many (23%) astroglia exhibited spontaneous calcium oscillations whose frequency and magnitude increased after the addition of 10(-5) M ATP. Immunocytochemical staining indicated that the responses occurred in glial fibrillary acidic protein positive cells. We conclude that type 1 astroglia express the P2Y purinergic receptor which regulates IP production and calcium mobilization.

Type 1 astroglia have been reported to exhibit in excess of 20 different neuroligand receptors in vitro. The aim of this study was to determine if astroglia, like neurons, are heterogeneous with respect to their ability to respond to different neuroligand receptor agonists. Type 1 astroglia were loaded with the calcium indicator dye fura-2 and the influence of six different neuroligands on their intracellular calcium levels was examined using a video-based imaging system. Each of the six different neuroligands tested increased calcium levels in a subpopulation of glial fibrillary acidic protein immunopositive cells (astroglia). The percentage of cerebral cortical type 1 astroglia responding to a given neuroligand varied with the agonist and generally followed the order: 2-methylthio-ATP greater than phenylephrine greater than carbachol = serotonin greater than glutamate = histamine. The results also indicate that a single astroglial cell can respond to one agonist with a sustained rise in calcium levels and to an alternate agonist with oscillations in calcium levels. The pharmacological heterogeneity evident among astroglia does not appear to depend on cell proliferation or association with neurons. The results of our studies indicate that cultures of cerebral cortical type 1 astroglia are composed of distinct subsets of cells that can be distinguished by qualitative differences in their ability to respond to specific neuroligands with a rise in intracellular calcium.

We have used the CA++ indicator dye fura-2 AM and computerized imaging systems to investigate adrenergic regulation of intracellular calcium in cultured cerebral type 1 astroglia. We have found that norepinephrine (NE) and other adrenergic agonists stimulate increases in intracellular calcium in over 80% of type 1 astroglia tested. A wide range in effective NE concentrations was seen. With sufficient agonist concentrations the calcium response was biphasic, exhibiting an initial sharp peak followed by a sustained calcium elevation. This secondary component was sensitive to reductions in extracellular calcium concentrations and dependent on the continued presence of agonist. Pharmacological studies indicated that astroglial calcium responses were mediated by alpha 1- and alpha 2-adrenergic receptors. At times these two receptor subtypes appeared to underlie calcium responses by the same cells, whereas other cells only responded to stimulation of one or the other subtypes of alpha-adrenergic receptor. Finally, we have also observed spontaneous and agonist-evoked oscillations in astroglial calcium levels. The major findings of these studies indicate that 1) astroglial cells respond to alpha-adrenergic receptor stimulation with increased intracellular calcium, 2) these responses can be mediated by alpha 1-and/or alpha 2-adrenergic receptors, and 3) subpopulations of cerebral type 1 astroglia exist with respect to alpha-adrenergic receptor expression.

Microglia are the immune cells of the CNS. In the normal adult mammalian brain, the majority of these cells is quiescent and exhibits a ramified morphology. Microglia are perhaps best known for their swift transformation to an activated ameboid morphology in response to pathological insults. Here we have observed the responsiveness of these cells to events surrounding the normal activation of neurosecretory neurons in the hypothalamic supraoptic nucleus (SON), a well studied model of structural plasticity in the CNS. Neurons in the SON were activated by substituting 2% saline for drinking water. Brain sections were collected from four experimental groups [controls (C), 2 d-dehydrated (2D), 7 d-dehydrated (D7), and 7 d-dehydrated/21 d-rehydrated animals (R21)] and stained with Isolectin-B4-HRP to visualize microglial cells. Based on morphological criteria, we quantified ramified, hypertrophied, and ameboid microglia using unbiased stereological techniques. Statistical analyses showed significant increases in the number of hypertrophied microglia in the D2 and D7 groups. Moreover, there was a significant increase in the number of ameboid microglia in the D7 group. No changes were seen across conditions in the number of ramified cells, nor did we observe any significant phenotypic changes in a control area of the cingulate gyrus. Hence, increased morphological diversity of microglia was found specifically in the SON and was reversible with the cessation of stimulation. These results indicate that phenotypic plasticity of microglia may be a feature of the normal structural remodeling that accompanies neuronal activation in addition to the activation that accompanies brain pathology.

Publisher Summary This chapter reviews that structural plasticity of astrocytes in the normally functioning brain is widespread. Two of the best-studied regions where structural plasticity occurs are the supraoptic nucleus (SON) and posterior pituitary. It discusses the recent developments in understanding of how this structural remodelling, including new finding that show microglia also participate in structural plasticity of the SON. The chapter also introduces other brain areas, where structural plasticity of astrocytes has been demonstrated. Structural plasticity of glia, predominantly that of astrocytes, occurs throughout the nervous system. Sites, where structural plasticity of astrocytes has been documented in normal brains include the hippocampus with long term potentiation induction in the suprachiasmatic nucleus across the diurnal cycle, in the cerebellar cortex with motor learning in the arcuate nucleus of the rat and monkey, across changing estrogen levels, and extensively, in the hypothalamo-neurohypophyseal system (HNS) in response to diverse conditions leading to the synthesis and release of the peptides oxytocin (OX) and vasopressin (VP). The chapter concludes that the factors that are investigated in the SON of the hypothalamus include reorientation of astrocytes, reentry of glial cells into the cell cycle, downregulation of morphoregulatory molecules, dissolution of the basal lamina, changes in the GFAP, concomitant changes in expression of GFAP message, and changes in the population of resident microglia.

A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years.Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years.The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF.All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation.A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year.There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups.All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.

It has been known for more than twenty years that changes in glial coverage of magnocellular neurones in the hypothalamo-neurohypophysial system accompany activation of those neurones. This led to the so-called 'glial retraction hypothesis.' However, until recently, little has been established as to how this structural plasticity of astrocytes develops. This paper will explore a number of hypotheses and supporting data concerning these changes.

Ultrastructural studies of the supraoptic nucleus (SON) of the hypothalamus suggest that an active retraction and extension of astrocytic processes (structural plasticity) from between magnocellular neuroendocrine neurons plays a role in the release of oxytocin, vasopressin, or both peptides that accompanies parturition, lactation, and dehydration. In support of this, Salm et al. (1985) previously demonstrated a lactation-associated reduction in immunoreactive glial fibrillary acidic protein (GFAP), an astrocyte-specific cytoskeletal constituent. To determine if similar changes occur in response to dehydration, and if they are reversible, the present study examined GFAP-immunoreactivity (IR) in the SON under various hydration states. Rats were dehydrated for 7 days by substitution of drinking water with 2% saline (n = 3), or dehydrated for 7 days followed by 7 days of rehydration (n = 3). A control group (n = 3) with free access to tap water was used for comparisons. The optical density of GFAP-IR was obtained from the SON, globus pallidus, and lateral hypothalamic regions. The areas of the ventral glial limitans subjacent to the SON (SON-VGL) and of linearly equivalent segments of glial limitans more distant from the SON were also determined. Dehydration resulted in a significant reduction in GFAP-IR in the SON compared to control and rehydrated levels. We also found that the area of the SON-VGL was significantly larger than that of linearly equivalent segments of glial limitans elsewhere and that it was significantly reduced in dehydrated rats, returning to control levels with rehydration. GFAP-IR and glial limitans thickness in regions unrelated to body fluid homeostasis lateral to the SON, overlying to dorsal cortex, and subjacent to the optic chiasm were not significantly changed by hydration state. These results are similar to the changes of GFAP-IR reported for lactating rats and provide further evidence for a role of structural plasticity of astrocytes in events surrounding the selective functional activation of local neurons.

The present study evaluated the expression of tenascin by astrocytes in the supraoptic nucleus and associated ventral glial limitans (SON-VGL) under conditions that induce reversible changes in neuronal organization (dehydration and rehydration). Immunostaining of astroglia cultured from rat neonatal SON-VGL confirmed that these cells are capable of both expressing and secreting tenascin. Observations of immunostained tissue sections from adult rats revealed tenascin immunoreactivity primarily in the VGL and dendritic zone, subjacent to SON neuronal somata. Comparison of immunostained tissues from hydrated and dehydrated animals showed an apparent decrease in the intensity of immunostaining with dehydration. Subsequent Western blots of similar tissues confirmed the presence of the 210-220-kDa tenascin protein in the SON-VGL. SON-VGL tissues from control, dehydrated, and rehydrated rats were then studied by using SDS-PAGE and quantitative gel densitometry. A consistent decrease in tenascin concentration was observed by 6 days of dehydration that, with rehydration, reversed back toward or beyond control levels. Together, these observations indicate that SON-VGL astrocytes variably express tenascin and that this protein may play a role in adult SON plasticity.

The mitotic activity astrocytes in the adult central nervous system (CNS) is of interest due to their roles in gliosis and tumorigenesis, and their potential in aiding recovery of function following injury or disease. The posterior pituitary offers a potentially powerful model to study proliferation in vivo, since its resident astrocytes, called pituicytes, have been reported to divide concurrently with hormone release from the neurosecretory terminals there. Our aim in this study was to confirm and characterize this proliferative response during dehydration and rehydration in fully adult animals, using contemporary techniques. Adult male rats were given 2% saline in substitution for water for 0–9 days. Proliferation of pituicytes was quantified in tissue sections triple-labeled with the proliferation marker, 5-bromodeoxyuridine (BrdU), the astrocyte marker glial fibrillary acidic protein (GFAP), and the DNA marker 4,6, diamidino-2-phenylindole, HC1 (DAPI). A robust proliferative response began within three days of dehydration and continued at a constant rate thereafter. In animals allowed to rehydrate, this response continued. After 9 days of dehydration, approximately 35% of pituicytes had participated in mitosis. While cell density remained constant across conditions, a reversible increase in posterior pituitary area was seen, suggesting that some cell death also occurs simultaneously. A significant proportion of non-pituicytes also underwent similar changes. These results indicate that pituicytes in the adult posterior pituitary retain characteristics necessary for reentering the cell cycle in response to local factors present during neurosecretory activity. We hypothesize that this proliferative response is directly related to the morphological changes previously reported for these cells under activating conditions. © 1995 Wiley-Liss, Inc.

The score card shown on pages 282-83 has been prepared for the purpose of supervising teaching, not teachers. Moreover, this card has been prepared for the purpose of supervising only one kind of recitation, namely, the question-and-answer type. It is in the personal interview that the supervisor feels the need of definite data on which to base his statements. Generalities merely create differences of opinion. In discussing teacher problems, the supervisor should avail himself of every opportunity to supplant mere generalities with specific facts. Along with standard tests and experimental studies, schemes for rating the teacher and judging the recitation will go far toward supplying these facts to the supervisor. The purpose of this score sheet is not so much to obtain a rating of the individual teachers as to supervise and aid actual classroom teaching. This phase is too often neglected in the secondary schools of today. We assume that high-school teachers are specialists in their particular fields and consequently need no supervision or assistance. Some school authorities have even gone so far as to consider it a mark of weakness on the part of high-school teachers if they ask for assistance along this line. With these facts in mind, the writer has attempted to formulate a series of questions which can be checked by the principal or supervisor during his visit to the classroom; these questions can be checked in duplicate and one copy left with the teacher, who should consider it as a basis for a conference with the principal, later the same day if possible. In fact, the score sheet should be taken up at one of the first teachers' meetings of the year and discussed with the teachers, in order that they may become familiar with it and be able to use it as a self-improving device.

A primary task of lipid chemistry is the elucidation of the following problems of membrane biochemistry: 1. The structure and properties of membrane lipids 2. The molecular basis and the dynamics of lipid-protein binding in those structures in which their interaction has been proved. Because a detailed structural analysis of any membrane lipid is now technologically possible, our present efforts are aimed at the elucidation of lipid-lipid and lipid-protein interactions at the molecular level, utilizing potent methods applied to reasonable artificial and biological models of as little complexity as possible.

Electron-microscopic evidence indicates that during conditions of high hormone demand such as lactation there is a dramatic reduction in the number of fine glial processes which are normally interposed between magnocellular neuroendocrine cell somata in the supraoptic nucleus (SON). The purpose of this study was to corroborate these data at the light-microscopic level and to gain some insight into what underlying events might accompany these apparent morphological changes. The distribution of the glial fibrillary acidic protein (GFAP), an intermediate filament component of the astrocytic cytoskeleton, was visualized in lactating or estrous rats using peroxidase-antiperoxidae immunocytochemistry. Computerized image analysis was employed to determine and compare the staining distributions of this protein for the two groups of rats. Statistical analysis revealed a redistribution of GFAP immunostaining in the SONs of lactating animals as compared to controls. No differences in staining were found in a control area dorsolateral to SON. The pattern of change was to a less dense, more homogeneous distribution of GFAP in lactating rats, a change which could be interpreted as reflective of a reduction in the number of densely staining glial processes.

Astrocytes are the most numerous cell type in the central nervous system. When cultured, these cells express a wide variety of receptors for neurotransmitters. Nonetheless, it has yet to be firmly established that adult astrocytes in situ express receptors for neurotransmitters. In this report the technique of combined receptor autoradiography and immunocytochemistry has been applied to isolated astrocytes from adult animals to examine beta-adrenergic receptor (beta-AR) expression by these cells. It is shown that fibrous and protoplasmic astrocytes isolated from adult rat cerebral cortices specifically bind the beta-AR ligand iodocyanopindolol and that this binding is inhibited by the beta-AR ligands propranolol and isoproterenol. These results indicate that at least two of the major morphological subtypes of adult astrocytes express beta-ARs.