Biomedical subjects

M Carmona

Publications and source records attributed to M Carmona.

At least 37 records · Page 2Linked to original sources

PubMed2001

Phosphorylated c-MYC expression in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration.

Phosphorylated c-Myc (c-Myc-P) expression has been examined by immunohistochemistry, using an antibody that recognizes phosphorylated c-Myc at Thr58 and Ser62, in the brains of Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and age-matched control cases, as well as in human medulloblastomas and central neuroblastomas. Strong c-Myc-P immunoreactivity was seen in dystrophic neurites and neurones with neurofibrillary tangles in AD, and in neurones and glial cells bearing abnormal tau deposits in PiD, PSP and CBD. Previous studies have shown active Ras and increased mitogen-activated protein kinase (MAPK/ERK) expression in neurones and glial cells with abnormal tau deposition in AD and other tauopathies. Since MAPKs phosphorylate c-Myc at Thr58 and Ser62, these observations implicate the Ras/MAP kinase pathway in c-Myc phosphorylation and accumulation in AD and other tauopathies. Previous studies have also shown activation of cell cycle associated proteins in neuronal death. The present results have shown colocalization of nuclear c-Myc-P and active, cleaved caspase-3, a major executioner of apoptosis, in medulloblastomas and central neuroblastomas, thus suggesting phosphorylated c-Myc expression in caspase-3-dependent apoptosis of tumour cells. However, no evidence of caspase-3 activation has been observed in neurones and glial cells with strong phosphorylated c-Myc immunoreactivity in AD, PiD, PSP and CBD. Therefore, it is not clear that the activation of the Ras/MAPK/c-Myc subprogramme leads to neuronal death in AD and other tauopathies.

Aged↗

PubMed2001

Phosphorylated map kinase (ERK1, ERK2) expression is associated with early tau deposition in neurones and glial cells, but not with increased nuclear DNA vulnerability and cell death, in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration.

Abnormal tau phosphorylation and deposition in neurones and glial cells is one of the major features in taupathies. The present study examines the involvement of the Ras/MEK/ERK pathway of tau phosphorylation in Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), by Western blotting, single and double-labelling immunohistochemistry, and p21Ras activation assay. Since this pathway is also activated in several paradigms of cell death and cell survival, activated ERK expression is also analysed with double-labelling immunohistochemistry and in situ end-labelling of nuclear DNA fragmentation to visualise activated ERK in cells with increased nuclear DNA vulnerability. The MEK1 antibody recognises one band of 45 kD that identifies phosphorylation-independent MEK1, whose expression levels are not modified in diseased brains. The ERK antibody recognises one band of 42 kD corresponding to the molecular weight of phosphorylation-independent ERK2; the expression levels, as well as the immunoreactivity of ERK in individual cells, is not changed in AD, PiD, PSP and CBD. The antibody MAPK-P distinguishes two bands of 44 kD and 42 kD that detect phosphorylated ERK1 and ERK2. MAPK-P expression levels, as seen with Western blotting, are markedly increased in AD, PiD, PSP and CBD. Moreover, immunohistochemistry discloses granular precipitates in the cytoplasm of neurones in AD, mainly in a subpopulation of neurones exhibiting early tau deposition, whereas neurones with developed neurofibrillary tangles are less commonly immunostained. MAPK-P also decorates neurones with Pick bodies in PiD, early tau deposition in neurones in PSP and CBD, and cortical achromatic neurones in CBD. In addition, strong MAPK-P immunoreactivity is found in large numbers of tau-positive glial cells in PSP and CBD, as seen with double-labelling immunohistochemistry. Yet no co-localisation of enhanced phosphorylated ERK immunoreactivity and nuclear DNA fragmentation is found in AD, PiD, PSP and CBD. Finally, activated Ras expression levels are increased in AD cases when compared with controls. These results demonstrate increased phosphorylated (active) ERK expression in association with early tau deposition in neurones and glial cells in taupathies, and suggest activated Ras as the upstream activator of the MEK/ERK pathway of tau phosphorylation in AD.

Aged↗

PubMed2001

Effect of policies directed at youth access to smoking: results from the SimSmoke computer simulation model.

OBJECTIVES: To develop a simulation model to predict the effects of youth access policies on retail compliance, smoking rates, and smoking attributable deaths. METHODS: A model of youth access policies is developed based on empirical research and a theory of perceived risk. The model incorporates substitution into other sources as retail sales are restricted, and is used to project the number of smokers and smoking related deaths. Various policies to limit youth access to cigarettes are evaluated, and we explore how efficient policies may be developed. RESULTS: The model predicts that a well designed and comprehensive policy that includes sufficient compliance checks, penalties, and community involvement has the potential to reduce the number of young smokers. Because smoking related deaths occur later in life, the effects on health are largely delayed. CONCLUSIONS: A well designed youth access policy has the ability to affect youth smoking rates in the short term, and will lead to savings in lives in future years. The ability of retail oriented policies to reduce youth smoking, however, is limited. Other tobacco control policies, including those directed at non-retail sources of cigarettes, are also needed.

Adolescent↗

PubMed2000

Autologous stem cell transplantation (ASCT) with immunologically purged progenitor cells in patients with advanced stage follicular lymphoma after early partial or complete remission: toxicity, follow-up of minimal residual disease and survival.

The role of autologous stem cell transplant (ASCT) in indolent lymphomas is a controversial issue. From 1994 to 1999, we performed ASCT with immunologically purged progenitor cells in 15 patients with advanced stage follicular lymphoma (FL) after early partial or complete remission. Results of the purging strategy and follow-up of minimal residual disease after transplant were analyzed with PCR amplification of bcl-2/IgH rearrangement for the t(14;18) translocation. A comparison of transplanted patients with a group of controls was carried out to evaluate differences in progression-free survival and overall survival. Eighty percent of patients received one chemotherapy regimen before ASCT and were in first remission. All the patients received cyclophosphamide plus hyperfractionated total body irradiation as the conditioning regimen. Nine patients were transplanted with bone marrow (BM) and six with peripheral blood progenitor cells (PBPC). Engraftment was delayed in one patient transplanted with BM. Two patients died during the transplant procedure. Ten of 12 evaluable patients were PCR positive in the BM for bcl-2 rearrangement at diagnosis. Six of them (60%) were still positive after chemotherapy, and one patient was transplanted with a positive hematopoietic product after purging. With a median follow-up of 27 months, six of eight evaluable patients still remain PCR negative in the BM. With a median follow-up of 4.7 years from diagnosis, progression-free survival was 83% (95% CI: 63-100). The risk of disease progression of non-transplanted patients was 19.2 times higher than that of transplanted patients (P = 0.01), but no differences were found in overall survival. Regarding patients in first remission, the risk of relapse was 12.6 times higher in non-transplanted than in transplanted patients (P = 0.04). This procedure seems to offer a good chance to achieve a PCR-negative state and prolonged freedom from recurrence. According to these results, prospective randomized trials are warranted.

Adult↗

PubMed2000

In vivo and in vitro effects of (p)ppGpp on the sigma(54) promoter Pu of the TOL plasmid of Pseudomonas putida.

The connection between the physiological control of the sigma(54)-dependent Pu promoter of the TOL plasmid pWW0 of Pseudomonas putida and the stringent response mediated by the alarmone (p)ppGpp has been examined in vivo an in vitro. To this end, the key regulatory elements of the system were faithfully reproduced in an Escherichia coli strain and assayed as lacZ fusions in various genetic backgrounds lacking (p)ppGpp or overexpressing relA. Neither the responsiveness of Pu to 3-methyl benzylalcohol mediated by its cognate activator XylR nor the down-regulation of the promoter by rapid growth were affected in relA/spoT strains to an extent which could account for the known physiological control that governs this promoter. Overexpression of the relA gene [predicted to increase intracellullar (p)ppGpp levels] did, however, cause a significant gain in Pu activity. Since such a gain might be the result of indirect effects, we resorted to an in vitro transcription system to assay directly the effect of ppGpp on the transcriptional machinery. Although we did observe a significant increase in Pu performance through a range of sigma(54)-RNAP concentrations, such an increase never exceeded twofold. The difference between these results and the behavior of the related Po promoter of the phenol degradation plasmid pVI150 could be traced to the different promoter sequences, which may dictate the type of metabolic signals recruited for the physiological control of sigma(54)-systems.

Amino Acids↗

PubMed1999

Recruitment of RNA polymerase is a rate-limiting step for the activation of the sigma(54) promoter Pu of Pseudomonas putida.

The activity of the sigma(54)-promoter Pu of Pseudomonas putida was examined in vitro with a DNA template lacking upstream activating sequences, such that RNA polymerase can be activated by the enhancer-binding protein XylR only from solution. Although the transcription activation pathway in this system lacked the step of integration host factor (IHF)-mediated looping of the XylR.DNA complex toward the prebound RNA polymerase, IHF still stimulated promoter activity. The positive effect of IHF became evident not only with XylR from solution, but also with other sigma(54)-dependent activators such as NtrC and NifA. Furthermore, an equivalent outcome was shown for the nonspecific DNA-binding protein HU. This stimulation of transcription in the absence of the enhancer was traced to the recruitment of RNA polymerase (i.e. increased efficiency of formation of closed complexes) brought about by IHF or HU binding. Thus, under limiting concentrations of the polymerase, the factor-mediated binding of the enzyme to Pu seems to enter a kinetic checkpoint in the system that prevents the XylR-mediated formation of an open complex.

Bacterial Proteins↗

PubMed1999

Ex-vivo expansion and maturation of CD34-positive hematopoietic progenitors optimization of culture conditions.

The aim of this study was to look for an ex vivo culture system for clinical application. We evaluated the ex vivo expansion of peripheral blood CD34+ cells in gas-permeable bags and whether or not an exogenous protein source would be required in these kind of cultures. We also evaluated maturation of the cells during culture. Cells were cultured for 15 days in medium supplemented with SCF, G-CSF, IL3 and IL6. The bags supported the expansion of hematopoietic cells in a similar manner to small scale flasks system: (a) the expansion means of total nucleated cells on day +5 were 12.5-fold for bag versus 5-fold for flask, on day +10 were 44.12-fold for bag versus 41-fold for flask and on day +15 were 67.7-fold for bag versus 84.2-fold for flask, (b) the peak values of CFU-GM were reached on day +10 (9.2-fold for bag vs. 12-fold for flask), and (c) maximal expansion of CD15+/CD11b- population occurred on day +10 (517.5-fold for bag vs. 2959.2-fold for flask). So, we did not find any advantages by culturing further than day +10. We subsequently investigated the use of serum-free medium. The study showed better results when we used medium supplemented with autologous plasma versus serum-free system. In summary, these data described a strategy of culture clinically feasible and safe, using gas-permeable bags, and the kinetics and differentiation of neutrophils and neutrophil precursors from selected CD34+ cells in liquid cultures. Ex vivo expansion of this population might result in earlier engraftment as compared with that for selected stem cells alone.

Adult↗

PubMed1999

Immunomagnetic bone marrow (BM) and peripheral blood progenitor cell (PBPC) purging in follicular lymphoma (FL).

Twenty-nine B cell follicular lymphoma (FL) patients had their BM (n = 12) or PBPC (n = 17) purged using a panel of monoclonal antibodies and immunomagnetic beads (IMB). The median recovery of nucleated cells (NC) and CD34+ cells was 59.3% (40.5-74) and 56.1% (30.8-82.9) in BM and 77.2% (64.7-88.3) and 73.5% (61.5-98.6) in PBPC (P<0.0005). A median of >1.62 and >1.02 log of target cell depletion was achieved as judged by flow cytometry analysis in BM and PBPC, respectively. Of 29% of initial harvests that had a bcl2 PCR-amplified signal, 37.5% became PCR negative in the final purged products. Absorbed cells containing IMB-target cell complexes gave bcl2 rearrangement signal in 20% of samples in which the start and final purged components were negative. Twenty-three of 26 patients receiving an autologous purged product are evaluable for engraftment. Median time to reach an ANC >0.5x10(9)/l and platelet count >20x10(9)/l was 21 (11-43) and 41 days (13-70) for BM (n = 9) and 14 (10-31) and 14 (8-37) for PBPC (n = 14) autografted patients (P = 0.01 and 0.001). One patient did not engraft and was rescued with a back-up BM. These data demonstrate that this indirect immunomagnetic technique is able to achieve a high grade of lymphoma cell depletion in BM and PBPC and that these purged products are capable of rapid engraftment after autologous transplantation.

Adult↗

PubMed1999

Cardiac involvement and molecular staging in a fatal case of mycosis fungoides.

Polymerase chain reaction (PCR) amplification of T-cell receptor-gamma gene rearrangement was used for molecular staging in a case of primary cutaneous T-cell lymphoma (CTCL) with fatal evolution. Although initial evaluation was negative for systemic involvement, the patient died due to heart failure. Autopsy findings revealed lymphomatous myocardial infiltration, but other tissues and organs examined, including lymph nodes, liver, spleen, lung and bone marrow, appeared to be free of disease. Molecular analysis from frozen samples obtained during the initial evaluation, as well as paraffin-embedded material obtained during autopsy, revealed the presence of clonal rearranged bands in all tissues examined except the bone marrow. Subsequent hybridization of PCR products with a tumour-specific oligoprobe confirmed the PCR results, suggesting widespread dissemination of the lymphomatous process. The use of molecular analysis can add significant information about the extent of disease in patients with CTCL and may be helpful in the establishment of therapeutic options.

Fatal Outcome↗

PubMed1999

Involvement of the FtsH (HflB) protease in the activity of sigma 54 promoters.

The effect of FtsH, an essential inner membrane-bound protease, in the regulation of the sigma 54-dependent Pu promoter has been examined in vivo. Escherichia coli cells lacking FtsH failed to activate a Pu-lacZ fusion in response to the cognate enhancer-binding protein XylR. However, the intracellular concentrations of XylR and sigma 54, as well as their apparent physical integrity were the same regardless of the presence or absence of the protease. The loss of Pu activity in FtsH-minus cells was not due to the imbalance between sigma factors caused by the lack of the protease. ftsH mutants could not grow in media with glutamine as the only nitrogen source and failed also to induce the sigma 54 promoters PnifH by NifA and PpspA by PspF. These lesions were fully complemented by a ftsH+ plasmid. Therefore, part of the pleiotropic phenotype of FtsH-less cells corresponded to the lack of sigma 54 activity. Overproduction of sigma 54, however, restored both transcriptional activity of Pu and growth in glutamine of a ftsH strain. These observations suggested that the activity of sigma 54 is checked in vivo by an interplay of factors that ultimately determine the performance of cognate promoters under given physiological conditions.

ATP-Dependent Proteases↗

PubMed1997

High-titer retroviral vectors containing the enhanced green fluorescent protein gene for efficient expression in hematopoietic cells.

Retroviral vectors constitute the most efficient system to deliver and integrate foreign genes into mammalian cells. We have developed a producer cell line that yields high titers of amphotropic retroviral vectors carrying the enhanced green fluorescent protein (EGFP) gene, a codon humanized, red-shifted variant of the green fluorescent protein (GFP) gene, which can be used as a selectable marker. We have used a hybrid vector that has been shown to efficiently drive gene expression in hematopoietic cells. Virtually all murine and human cell lines and primary human hematopoietic cells tested were transduced with varying efficiency after incubation with vector-containing supernatants. Human CD34(+) cells obtained from cord blood or aphereses products were transduced using a protocol that involves daily addition of vector-containing supernatants for 6 consecutive days. At day 6, up to 16% of the cells expressed EGFP, as assessed by flow cytometry. Sorted EGFP-expressing cells were able to produce fluorescent hematopoietic colonies. EGFP's main advantages are its fast flow cytometry determination and the possibility of cell sorting and simultaneous evaluation of the transduction efficiency along with other phenotypic markers.

3T3 Cells↗

PubMed1997

DNA bending and the initiation of transcription at sigma54-dependent bacterial promoters.

We have examined the effects on transcription initiation of promoter and enhancer strength and of the curvature of the DNA separating these entities on wild-type and mutated enhancer-promoter regions at the Escherichia coli sigma54-dependent promoters glnAp2 and glnHp2 on supercoiled and linear DNA. Our results, together with previously reported observations by other investigators, show that the initiation of transcription on linear DNA requires a single intrinsic or induced bend in the DNA, as well as a promoter with high affinity for sigma54-RNA polymerase, but on supercoiled DNA requires either such a bend or a high affinity promoter but not both. The examination of the DNA sequence of all nif gene activator- or nitrogen regulator I-sigma54 promoters reveals that those lacking a binding site for the integration host factor have an intrinsic single bend in the DNA separating enhancer from promoter.

Bacterial Proteins↗

PubMed1997

Repopulation of circulating T, B and NK lymphocytes following bone marrow and blood stem cell transplantation.

A variety of T, B and natural killer (NK) cell subsets defined by surface markers were analyzed by double immunofluorescence flow cytometry in the peripheral blood of patients following autologous bone marrow transplantation (ABMT, n = 14), autologous peripheral blood stem cell transplantation (PBSCT, n = 10) and allogeneic bone marrow transplantation (allo-BMT, n = 6). Patients following ABMT were divided in 2 groups, those who did not received G-CSF post-transplant (ABMT, n = 6) and those who did (ABMT + G, n = 8). All patients following PBSCT or allo BMT received G-CSF. In all the groups prolonged significant decreases with respect to normal numbers were observed for the T CD3+, CD2+ and CD25+ subsets, more profound for the CD4+ subset but less for the CD8+ subset, especially following PBSCT (only decreased at 1 month). A significant expansion of the CD3+CD57+ and CD8+CD57+ phenotypes was noticed between 9 and 12 months following ABMT, the group of longer follow-up. Long-lasting expansion of the NK-like CD3+CD56+ and CD3+CD16+ subsets was also observed. The B CD19+ and CD20+ subsets had a significant overexpression from 4 months after ABMT, showing a normally balanced Igk+:Ig1+ ratio. Concordantly, the HLA-DR+ and HLA-DQ+ subsets showed significant increases. The NK CD56+ and CD16+ subsets had a faster recovery than the T or B subsets in all the groups. However, the CD3-CD56+, CD3-CD16+, CD16+CD56+, CD3-CD8+, and especially the CD3-CD57+, CD16+CD57+, and CD56+CD57+ subsets had a slower recovery than the global CD56+, CD16+, or CD57+ subsets. The biological and clinical implications of these findings are discussed.

B-Lymphocyte Subsets↗

PubMed1997

Is rhodamine 123 an appropriate fluorescent probe to assess P-glycoprotein mediated multidrug resistance in vinblastine-resistant CHO cells?

Cellular drug resistance, which involves several mechanisms such as P-glycoprotein (P-gp) overexpression, kinetic and metabolic quiescence, or the increase in the intracellular levels of glutathione, limits the effectiveness of cancer treatment. It has been reported that functional assessment of the cationic dye rhodamin 123 (Rho123) efflux reveals accurately the drug-resistant phenotype. To study cellular drug resistance, we have obtained a CHO-K1 derived cell line resistant to vinblastine by means of multistep selection. This cell line (CHOVBR) displays high reactivity with a monoclonal antibody (MAb) (C219) directed against an internal domain of P-gp, and an active Rho123 efflux, as shown by parallel flow cytometric and fluorometric assays. However, under similar experimental conditions, the drug-sensitive parental cell line CHO-K1 (as well as the myeloblastic KG1 and KG1a cell lines), was also able to pump Rho123 out. These parental CHO-K1 cells had a very low reactivity against the C219 Mab, as confirmed by Western blot analysis. Both vinblastine and verapamil inhibited Rho123 efflux in CHO-K1 cells, but had no effect on CHOVBR cultures. Also, deprivation of vinblastine for one month did not affect Rho123 efflux in these cells. Our results suggest that the activity of P-gp appears to be essential, but not sufficient to confer drug resistance, and that Rho123-based functional assays of drug resistance should be evaluated for each cellular experimental model.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

[Evaluation of bone-marrow cell cryopreservation using long-term cultures].

PURPOSE: Autologous bone marrow transplantation (ABMT) is frequently used in the treatment of neoplastic diseases. It involves several manipulations of bone marrow cells in vitro that can damage the stem cells responsible for grafting. Long-term marrow cultures (LTBMC) support hematopoiesis in vitro for several weeks. We analyzed the effect of bone marrow cryopreservation on haematopoiesis when using this technique. PATIENTS AND METHODS: 9 bone marrow from healthy donors (Group A) and 15 from patients who were about to undergo ABMT (Group B) were assayed in LTBMC. In all cases, cultures were initiated after cell concentration and also after cryopreservation in group B patients. Adherent cell layer formation, supernatant nucleated cell counts and CFU-GM growth from the non-adherent fraction were assessed. Statistical analysis were evaluated using Wilcoxon test for paired results and Mann-Whitney test for unpaired results. RESULTS: No significant statistical differences were observed when the LTBMC from group A controls were compared to those from group B patients prior to cell cryopreservation. There was a significant statistical difference between cumulative cell recoveries among the cultures developed prior to and after cryopreservation of BM cells from group B patients. CONCLUSION: The results supports the use of LTBMC to obtain information on the extent of the injury of BM cells during manipulations.

Adipose Tissue↗

PubMed1997

Genotypic analysis of cutaneous T-cell lymphoma: a comparative study of Southern blot analysis with polymerase chain reaction amplification of the T-cell receptor-gamma gene.

The diagnosis of early cutaneous T-cell lymphoma (CTCL) is a difficult point in dermatology. Recently, Southern blot analysis (SBA) and polymerase chain reaction (PCR) have been used to detect clonality in initial lesions in which clinical and histological findings are unspecific. Forty-one samples from 25 patients with CTCL were investigated for the presence of T-cell receptor-gamma gene rearrangement using a nested PCR technique and analysed by polyacrylamide gel electrophoresis (PAGE). Conventional SBA was also performed on 28 samples from 20 of these patients. In addition, 20 samples corresponding to patients with large plaque parapsoriasis (LPP), cutaneous B-cell lymphoma (CBCL) and eczema were analysed by PCR in the same way as were the CTCL specimens. Most of the CTCL specimens (81%) showed clonality on PCR analysis. Among patients with mycosis fungoides, 71% of initial patch lesions and 100% of plaques and tumours showed clonal disease. Clonality could be detected in three of four histologically negative post-treatment lesions. Clonal rearrangement was detected in one of three patients with LPP and in three of 10 patients with CBCL. None of the samples corresponding to patients with eczema showed positive results. SBA was significantly less sensitive than PCR in detecting clonality in CTCL patients (42% among early disease and 60% among advanced cases). The results indicate that this PCR/PAGE technique is a reliable and useful method for the detection of clonality in early skin lesions of CTCL patients and probably in the identification of silent extracutaneous involvement.

Adolescent↗

PubMed1996

Activation of transcription at sigma 54-dependent promoters on linear templates requires intrinsic or induced bending of the DNA.

The initiation of transcription (open complex formation) on supercoiled DNA templates carrying the sigma 54-dependent promoters glnAp2 or glnHp2 can be readily activated by NR1-phosphate bound to sites located 100 bp upstream from the transcriptional start site. In the case of glnAp2, open complex formation can also be activated by NR1-phosphate on a linear template, but in the case of glnHp2 activation on a linear template requires in addition to NR1-phosphate, a DNA-bending protein such as the histone-like protein HU or integration host factor (IHF). Moving the binding sites for NR1 200 bp further away from glnHp2 allows transcription to be activated equally well in the absence or presence of HU, and in this case IHF inhibits the open complex formation. Furthermore, replacement of the DNA segment separating the binding sites for NR1 from glnAp2 by a random sequence of bases of equal length, does not reduce open complex formation on supercoiled DNA but prevents open complex formation on linear DNA unless HU is provided. These observations indicate that with binding sites for NR1 located in their usual position, 100 bp from the transcriptional start site, the DNA segment separating these sites from the promoter must be either intrinsically bent or bent by HU or, in the case of glnHp2, by IHF to allow contact between activator and the sigma 54-RNA polymerase-promoter complex. Computer simulation of the shape of the DNA suggests that in the case of glnAp2, but not of glnHp2 or the altered glnAp2, this segment has an intrinsic curvature of 70 degrees.

Bacterial Proteins↗

PubMed1996

CREB-1 and CREB-2 immunoreactivity in the rat brain.

This study is focused to learn about the cellular localization of transcription factors binding to the cAMP response element-CREBs-in the brain of normal rats and in animals subjected to excitotoxic cell damage. For this purpose, CREB-1 and CREB-2 immunoreactivity is examined in the developing and adult rat brain under physiological conditions, and following systemic kainic acid (KA) injection at convulsant doses in the adult, as a validated experimental model of excitotoxic injury. CREB-1 immunoreactivity is constitutively expressed in periventricular glia and Bergmann glia, and appears in reactive astrocytes following KA-induced excitotoxic cell damage. In contrast, CREB-2 is constitutively expressed in all neurons of the cerebrum, cerebellum and brain stem in the developing and adult brain. CREB-2 immunoreactivity is not increased following KA excitotoxic cell damage. These results demonstrate that CREB-1 and CREB-2 in the brain of the rat are localized in separate cellular compartments and that their expression is differentially regulated in pathologic states.

Animals↗