Rutgers et al. [33] demonstrated that changes in BALF do not reflect changes in the lung tissue. Because airway inflammation was induced in all age groups by i.n. sensitization with OVA in adjuvant followed by OVA challenges, our study suggests that differences in BALF

and tissue inflammation may be influenced by age. The percentage of PAS staining cells was affected by age in the same way as epithelial DAPT cell shedding (as observed in BALF) and, thus, suggests that the pulmonary epithelium is actively involved in the allergic airway response in the i.n. model. In the i.p. model, the largest epithelial shedding was also observed in 6-week-old mice. Our study was designed to cover an age span which is usually

employed in Caspase-independent apoptosis experimental research. The largest differences for both models were between the 1-week-old mice and the older mice. However, the allergic response continued to change also from 6 to 20 weeks of age in the i.n. model. Other studies based on i.p. sensitization demonstrate both decreases [21] and increases [20, 24, 34] in IgE and airway inflammation within the age span investigated here. IFNγ has been described to increase with age, while TH2 cytokine responses decreased [20, 21], but we found no such pattern for IFNγ (Table 3). The published studies used BALB/c or C57Bl/6 mice, which may differ immunologically from the NIH/OlaHsd strain. We have previously shown that the NIH/OlaHsd strain is a good IgE producer [35, 36] and that the 10 μg OVA i.p. immunization produces comparable IgE and IgG1 patterns in the NIH/OlaHsd, BALB/cJ and C57Bl/6 strains although the antibody levels were higher in the NIH/OlaHsd strain (unpublished data). Although the observed sex differences in the NIH/OlaHsd strain

were comparable to those of the BALB/c and C57Bl/6 strains (see above and unpublished data), it is possible that strain differences may explain the discrepant observations on age. However, from our study, it must be concluded that the influence of age on specific IgE and allergy outcomes in two different Phospholipase D1 mouse models is highly dependent on immunization dose and route (Table 3). TH17 activity is generally associated with neutrophil and eosinophil inflammation in allergy [37, 38], but IL-17 has also been observed to downregulate pulmonary eosinophil recruitment during an active allergic response [39]. It was previously reported that following airway sensitization, cytokine production was low in SLNs in contrast to MLNs [40, 41]. Except for IL-17A, the same was observed in the present study. Further, we observed that MLN but not SLN cell numbers were affected by immunization with adjuvant. De Haar et al. [42] found that T cells from SLNs in contrast to lung-draining lymph nodes do not proliferate following i.n. sensitization with OVA and adjuvant.

5A and data not shown). However, a decrease in CXCR3 surface expression was observed. NK cells did not proliferate, displayed no change in GrzB levels and were unable to lyse K562 cells in response to LASV- and MOPV-infected MΦs (data not shown). NK-cell activation is triggered by some NK-cell surface molecules and receptors. The blockade of CD40L, NKG2D, NKp30, NKp44, or NKp46 with neutralizing Ab had no effect on the expression of NK-cell surface

molecules (data not shown). We show here that cell contacts between NK cells and infected MΦs are essential for activation of NK cells and increase cytotoxicity while they do not seem to be involved in the modulation of CXCR3 expression. We previously showed that LDK378 MΦs secrete type I IFNs in response to MOPV infection, but that only low levels of these compounds

are produced during LASV infection. CXCL9, CXCL10, and CXCL11 are secreted in response to type I and II IFNs and bind CXCR3. The presence of type I IFN and CXC chemokines was analyzed in the supernatants of NK/MΦ cocultures. In cocultures HIF inhibitor review with NK cells, MOPV-, and to a lesser extent LASV-, infected MΦs secreted significant amounts of type I IFN and CXCL11 (Fig. 5B). Neutralizing mAbs directed against IFN-R and IFNα were used to inhibit type I IFN, and NK-cell stimulation by CXCL9, CXCL10, and CXCL11 was prevented with neutralizing mAbs directed against CXCR3 or CXC chemokines themselves. Our experiments with an irrelevant Ab gave results similar to those reported in Fig. 2. The inhibition of type I IFN reduced the increase in CD69 and NKp30 expression (Fig. 5C). However, neutralizing mAbs against type I IFN induced a decrease

in CXCR3 surface expression, although this decrease was smaller than that obtained with the irrelevant Ab. Moreover, we observed a global increase in CXCR3 expression (Fig. 5C). NK-cell proliferation Megestrol Acetate and the intracellular GrzB expression induced by LASV- and MOPV-infected MΦs were also abolished by the blockade of type I IFN (data not shown). After CXCR3 neutralization, NK cells remained activated in terms of the upregulation of CD69 and NKp30, proliferation and enhanced GrzB expression (data not shown). Neutralizing mAbs against CXC chemokines gave similar results. In addition, they induced a decrease in CXCR3 surface expression, but smaller than that obtained with the irrelevant Ab. Thus, our findings demonstrate that the type I IFN secreted by MΦs are necessary for NK-cell activation during LASV and MOPV infection but CXC chemokines have minor effects. We developed a model of NK cells cocultured with infected APCs, for studies of the role of NK cells and the importance of interactions during LASV and MOPV infections. We used LPS-activated APCs as a positive control for the APC-mediated activation of NK cells. We confirmed that LPS did not activate NK cells directly (data not shown).

2A) and primary human T cells (Supporting Information Fig. 3A). TPEN potentially even slightly increased STAT5 phosphorylation in response to IL-2. In addition, treatment with zinc and pyrithione had no impact on STAT5-phosphorylation (Fig. 2A). It is important to consider that TPEN may not click here only chelate free zinc, but also interact with tightly protein bound zinc, such as in zinc fingers. This has recently been investigated

in vitro by monitoring the DNA-binding capacity of the Zn3-SP1 zinc finger transcription factor. TPEN removed zinc from zinc fingers in vitro, whereas incubation of LLCPK1 cells with 100 μM for 30 min had no effect on DNA-binding of Zn3-SP1. Even after 24 h, 30 μM TPEN were required to affect DNA binding 24. Consequently, the conditions used in our experiments are significantly lower than the ones shown to interfere with tightly protein bound zinc. In

light of the differential role of free zinc in ERK and STAT5 activation, an effect on IL-2R tyrosine phosphorylation seems unlikely as a mechanistic explanation, because it should affect both pathways in a similar manner. ERK is activated via a cascade originating from Tyr338 on the IL-2R β chain via the Shc/Grb2/SOS/Ras/Raf/MEK/ERK pathway 10. TPEN had no effect on the IL-2-induced activating phosphorylation of Raf on serine 338 (Fig. 2B). These results were confirmed in primary T cells, where TPEN had no effect on IL-2-induced Raf phosphorylation, but inhibited MEK1/2 and ERK1/2 phosphorylation in a concentration-dependent manner (Supporting Information Fig. 3A). This indicates that zinc signals regulate ERK signaling MLN8237 nmr downstream of Raf. Several members of the DUSP family and PP2A dephosphorylate ERK 13, and both types of phosphatases are inhibited by zinc 25–27. Therefore, we performed an assay to measure the impact of zinc on total phosphatase activity (Fig. 2C). There was a clear, concentration-dependent effect of zinc, but it Calpain was observed at significantly higher (micromolar)

concentrations than the nanomolar amounts found in intact cells (Supporting Information Fig. 1C). However, when free zinc in the lysate was measured with FluoZin-3, we found that the lysate buffers zinc by more than three orders of magnitude, resulting in concentrations in the nanomolar range (Fig. 2D). When these actual concentrations are considered, phosphatase inhibition is observed at physiologically relevant concentrations of free zinc (Fig. 2E). Next, we used an in vitro dephosphorylation assay to investigate the impact of zinc on MEK and ERK phosphorylation, showing that zinc protected both kinases from dephosphorylation (Fig. 2F). Notably, the effect on ERK was observed in the presence of the MEK inhibitor U0126, demonstrating that it was not simply a result of preserved MEK activity, but that dephosphorylation of both kinases was inhibited by zinc.

Serum MMCP-1 has been shown to be a marker for

mucosal mastocytosis and increased gut permeability [32] as well as for mast cell dependent intestinal inflammation [33]. A strong correlation between anaphylactic score and levels of MMCP-1 was found. However, cross-allergy did not reveal any signs of mast cell activation, as the levels of MMCP-1 in animals challenged with cross-reactive legumes were comparable with the levels of immunized, not challenged animals. This suggests selleck screening library that intestinal mast cells are less activated in the cross-allergic reactions observed. It has been reported that food induced anaphylaxis may depend more on macrophages and basophils than on mast cells [34], and more studies are needed to elucidate the roles of macrophages and basophils in cross-allergy. That no cross-reactivity could be observed in the PCA-test may also support the notion that cross-allergic reactions are not mediated through a mast cell dependent pathway. However, because of the functionality of the test, it could also be a reflection of the difference in affinity between epitopes. Two distinct mechanisms have been reported to induce systemic anaphylaxis in the mouse [35]. The classical pathway is mediated by allergen cross linking of IgE bound to the high affinity receptor (FcεRI) on mast cells. The alternative

pathway is thought to involve macrophages, FcγRIII, IgG antibodies and platelet activating factor [36]. A partial inhibition Tau-protein kinase of lupin specific IgG1 by peanut and soy and of fenugreek specific IgG1 by peanut was observed. A role for both IgE and Selleck Pexidartinib IgG1 in the cross-allergic responses in mice is therefore possible. Several studies have implied that both the classical and the alternative pathway of food induced anaphylaxis are involved simultaneously in mice, and that abrogation of one pathway only partially abrogates anaphylactic responses [37–39]. Tsujimura

et al. [40] demonstrated that basophils play a crucial role in IgG mediated anaphylaxis in their mouse model. It has also been reported that mast cells contribute to anaphylaxis through both IgE and IgG1, whereas macrophages contribute through IgG1 exclusively. The role of IgG1 in anaphylactic reactions in mice complicates the extrapolation of findings from mouse to man, as IgG-mediated anaphylaxis to food has not yet been described in man. The relevance to human anaphylaxis of the different pathways observed in mice needs to be investigated. Strait et al. have shown that although the IgE pathway is more sensitive and requires lower threshold levels of antigen for full activation, IgG mediated responses can also be severe [36, 41]. Our studies support the involvement of IgG1 in cross-allergy, while we were unable to confirm the involvement of IgE and mast cells.

[53] In vivo, newly generated peripherally find more induced Treg cells (within their first week) retain some plasticity (~ 50% maintain FOXP3 expression) whereas mature peripherally induced Treg cells achieve remarkable stability (~ 99%),[54] through mechanisms also involving CpG demethylation and autoregulation.[45] Hence, the plasticity and stability

phenotypes of distinct CD4 T-cell subsets are varied and developmentally regulated, and are controlled by transcriptional and epigenetic mechanisms. Several recent studies described here detail the relative roles and co-operative function of transcription factors in the initiation of T-cell subset differentiation and provide consensus on a primary role for ERFs in the early activation of enhancers and see more associated gene transcription. Indeed, with MRFs dispensable for much of the early Th cell transcriptional programme, and their relatively small regulatory footprint, some may see fit to question their ‘master’ status. However, while the in vitro studies are detailed and incisive in their control over comparative

conditions, it is crucial to consider what we have learned from in vivo loss-of-function studies, and to appreciate the function of MRFs in heritable maintenance of cellular phenotype, environmental responsiveness and plasticity (see above), as well as the complexity of Th cell phenotypic delineation in the organism. The role of FOXP3 in Treg cell biology illustrates this distinction in perspective well. Stimulation of naive CD4 T-cells through the TCR, together with environmental sensing of TGF-β and IL-2 can recapitulate a significant fraction of the Treg cell transcriptional signature, independent of Foxp3 expression.[35, 55] Perhaps this is analogous to the minor role for TBET, GATA3 and RORγt in initializing Th1, Th2 and Th17 enhancer activation and transcriptional signatures. However, in vivo, FOXP3 is critical for Treg cell identity and loss of Foxp3 in mature Treg cells results in their dedifferentiation, acquisition of alternative T-cell subset phenotype,

extensive immunopathologies and old death.[29, 56] Although we can appreciate the major role of ERFs in the initial differentiation process and the mechanistic insights gained from these studies, we can also acknowledge that the transcriptional programmes they induce are insufficient for complete in vivo, faithful, CD4 T-cell subset commitment and maintenance. As quantitatively inferior as their roles may seem in the initialization of enhancers and transcriptional programmes, minute features such as modulation of a key set of genes or establishment of stabilizing positive feedback loops, establish MRFs as central and defining factors in CD4 T-cell subsets. Studies of mechanisms employed by MRFs to orchestrate these cellular phenotypes are important for a general understanding of cellular differentiation and identity.

By contrast, on Ag-experienced CD8+ T cells we found that whereas IFN-α enhances the effector functions, it decreases fold cell expansion. No differences were found between IFN-α2b and IFN-α5 subtypes, suggesting redundancy in the system. The magnitude of the stimuli and

the inputs from different stimulatory/inhibitory receptors are critical parameters for the outcome of the T-cell response. Thus, the need of choosing a fixed dose of stimuli, a single costimulatory signal and few time points for the array analyses provides a limited and static picture of the transcriptional changes induced on human T cells. Despite this limitation, our array data provided a baseline definition of the IFN-α transcriptional effects on human CD8+ Fulvestrant T cells and will form the basis for further and more detailed studies. The results of the transcriptional analysis of human CD8+ T cells stimulated with IFN-α alone agree with previous studies of IFN-α stimulation of unfractionated PBL 18, 19. The overall similarity suggests that IFN-α imprints a common transcriptional

signature on the peripheral blood immune cell populations. Despite induction of relevant genes for effector functions, human CD8+ T cells treated only with IFN-α experienced no sign of activation. However IFN-α-derived signals synergize with signals elicited by CD3/CD28-triggering and promote the acquisition of effector functions on human CD8+ T cells. The biological meaning of the regulation of all these genes relevant for CD8+ T-cell functions by IFN-α itself

is still unknown. One possibility is that pre-exposure to IFN-α induces mRNA Anacetrapib that facilitate T-cell activation selleck chemical upon an eventual Ag encounter. Transcriptional analyses performed in human CD8+CD45RO− cells stimulated with Beads and either IFN-α2b and/or IFN-α5 show that, as a signal-3 cytokine, IFN-α regulates outstanding genes involved in the overall activation of T cells. Among these genes we found IL2. IL-2 is an important cytokine for survival, clonal expansion and differentiation of T cells 20. The fact that IFN-α also promotes the surface expression of CD25 strengthens the idea that IFN-α may promote the CD8+ T-cell response, at least in part, by inducing additional cytokines that could further stimulate CD8+ T cells in an autocrine manner. Importantly, the chief transcriptional signature of IFN-α, as a third signal, encompasses the up-regulation of transcripts involved in effector functions (IFNG, GZB and TRAIL) as well as production of chemokines (CXCL10 and CXCL11). A similar transcriptional signature has been found in OT1 cells stimulated in vitro with artificial DC and IFN-α 14, suggesting that IFN-α may promote the conversion of CD8+ T cells not only into highly effector cells but also into efficient chemotactic attractants of additional effector cells. This transcriptional effect was substantiated at the protein level and verified by functional assays.

marneffei may have different levels of power to survive under oxidative stress. “
“We investigated the epidemiological characteristics of both symptomatic and asymptomatic dermatophytic Protein Tyrosine Kinase inhibitor groin infections in 1970 women (age: 36.2 ± 12.5) during routine gynaecologic examinations. Bilateral groin samples were collected with sterile cotton swabs premoistened with sterile physiological saline. The samples were then separately inoculated onto Sabouraud glucose agar. Fungi were identified by sequencing the rDNA internal transcribed spacer region. Dermatophytes were recovered from

five patients (four Trichophyton rubrum and one Arthroderma vanbreuseghemii, 0.25%) with a diagnosis of asymptomatic carriers (four) and tinea inguinalis (one). In one case, groin carriage converted into tinea inguinalis after 3 weeks. Analysis of risk factors indicated that patients of at least 49 years were more likely to be positive for dermatophyte isolation (P = 0.002). In conclusion, groin dermatophyte carriage is more common than tinea inguinalis and can potentially convert into a symptomatic infection. “
“Invasive fungal diseases (IFD) are a major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). Their incidence

has risen dramatically in recent years. The diagnosis of IFDs remains difficult, even if the European Organisation for the Research and Treatment of Cancer (EORTC)/Mycosis Study Group (MSG) criteria find more are applied for study purposes to classify the www.selleckchem.com/GSK-3.html likelihood of these infections. These criteria have been developed for clinical trials, and their relevance in clinical settings outside a clinical trial remains unknown. We evaluated the impact of the EORTC/MSG criteria and a modification thereof for clinical purposes in patients with AML. We retro-spectively analysed 100 AML patients for

the occurrence of IFD. First, EORTC/MSG criteria were applied to classify the patients. Second, a modified version of these criteria already used in clinical trials was used to re-classify the patients. Fifty-seven patients developed an invasive fungal infection. Following the original criteria, 43% were classified as ‘possible’ IFD, whereas 7% each were classified as ‘probable’ and ‘proven’ IFD. After application of the modified criteria, only 9% of the patients remained ‘possible’ IFD, whereas 41% were ‘probable’. The occurrence of ‘proven’ cases was not altered by the modification and thus remained 7%. The application of modified criteria for the classification of IFD in AML patients leads to a considerable shift from ‘possible’ IFD (according to conventional EORTC criteria) towards ‘probable’ IFD. Nevertheless, neither the old EORTC criteria nor their modification was designed for use in clinical practice. As this study underscores the uncertainty in the diagnosis of IFD, the need for a clinically applicable classification is obvious.

Platelet factor 4 (PF4) was the first discovered CXC chemokine and is found

in platelet granules at very high concentration. In our current study, we provide strong evidence that PF4 is involved directly in liver innate immune response against IRI by regulating Th17 differentiation. PF4 deficiency aggravates Obeticholic Acid molecular weight liver IRI, as shown by higher serum alanine aminotransferase (ALT) levels and Suzuki scores. PF4 deficiency promotes Th17 response with higher levels of IL-23, IL-6, and IL-17, which aggravates liver IRI. Furthermore, PF4 deficiency limits suppressor of cytokine signaling 3 (SOCS3) expressions and PF4 fails to suppress expression of IL-17 in cells transfected with SOCS3 SiRNA. In conclusion, PF4 limits liver IRI through IL-17 inhibition via up-regulation of SOCS3.

This article is protected by copyright. All rights reserved. “
“T-cell re-constitution after allogeneic stem cell transplantation (alloSCT) is often dampened by the slow differentiation of human peripheral blood CD34+ (huCD34+) hematopoietic stem cells (HSCs) into mature T cells. This process may be accelerated by the co-transfer of in vitro-pre-differentiated committed T/NK-lymphoid progenitors (CTLPs). Here, we analysed the developmental potential of huCD34+ HSCs compared with CTLPs from a third-party donor in a murine NOD-scid IL2Rγnull model of humanised chimeric haematopoiesis. CTLPs (CD34+lin−CD45RA+CD7+) could be generated in vitro within 10 days upon co-culture of huCD34+ or cord blood CD34+ (CB-CD34) HSCs on murine OP9/N-DLL-1 Caspase pathway stroma cells but not in a novel 3-D cell-culture matrix with DLL-1low human stroma cells. In both in vitro systems, huCD34+ and CB-CD34+ HSCs did not give rise to mature T cells. Upon transfer into 6-wk-old immune-deficient mice, CTLPs alone did not engraft. However, transplantation of CTLPs together with huCD34+ HSCs resulted in rapid T-cell engraftment in spleen, bone marrow and thymus at day 28. Strikingly, at this early time point mature T cells originated exclusively from CTLPs, whereas

descendants of huCD34+ HSCs still expressed a T-cell-precursor most phenotype (CD7+CD5+CD1a+/−). This strategy to enhance early T-cell re-constitution with ex vivo-pre-differentiated T-lymphoid progenitors could bridge the gap until full T-cell recovery in severely immunocompromised patients after allogeneic stem cell transplantation. T-cell re-constitution critically influences outcome and treatment-related mortality after allogeneic stem cell transplantation (alloSCT). Normalization of the T-cell compartment after myeloablative therapy requires thymus-derived T-cell neogenesis; however, thymic resources are often compromised due to a damaged thymic microenvironment and older recipient age 1.

The five Proteasome inhibitor SLE patients ascertained to have TSGA10 autoantibodies were further analysed for autoantibodies against common APS1 autoantigens by ITT and immunoprecipitation. The female patient with high-titre autoantibodies against TSGA10 was found to have very low-titre GAD autoantibodies. One of the SLE patients with low-titre TSGA10 autoantibodies

was determined to have low-titre autoantibodies against both GAD and NALP5, whereas another patient had very low-titre autoantibodies against AADC. No autoantibodies were detectable against the autoantigens SCC, TPH, TH, 17-OH, CYP1A2, 21-OH or IA2. The single healthy blood donor with a positive TSGA10 autoantibody index did not have autoantibodies against any of the APS1 autoantigens. To determine the age at which TSGA10 autoantibodies manifest and if there are any fluctuations in TSGA10 autoantibody titres over the duration of the disease, ITT was conducted on

PARP inhibitor all serum samples collected from the five autoantibody-positive APS1 patients collected from the time of diagnosis (Fig. 2). Serum samples were available from a range of 4.5 years post-diagnosis to 23.5 years post-diagnosis with a median of 14.5 years for each patient. Three of the five patients had autoantibodies against TSGA10 from the first available serum sample at ages 7, 9 and 14 years. Seroconversion to a positive TSGA10 autoantibody index was observed in the remaining two patients at age 8 years and the second at 29 years of age. Autoantibody titres remained constant for each patient with every sample available with the longest follow-up period of 23.5 years. The tissue expression of TSGA10 was examined in various organs by quantitative PCR. TSGA10 mRNA was predominantly Tobramycin expressed in testicular tissue (Fig. 3), with expression also being detected in almost all tissues studied, albeit at very low levels in most organs.

Virtually undetectable TSGA10 mRNA expression was observed only in the heart, skeletal muscle, leucocytes and adrenal cortex. Pituitary manifestations are a rare feature of APS1 presenting as either single or multiple hormonal deficiencies. Autoantibodies against pituitary tissue have been repeatedly shown by immunofluorescence in the sera of APS1 patients, yet a major pituitary specific autoantigen remains to be identified. A cDNA clone encoding TSGA10 was isolated and identified as a minor autoantigen in APS1 from the immunoscreening of a human pituitary cDNA expression library. While conducting the present study, the TSGA10 autoantigen was also independently isolated from a human testis cDNA expression library and characterized using sera from within the same Finnish APS1 patient series [20].

This study was supported by Alzheimers Research UK and Alzheimer’s Society through their funding of the Manchester Brain Bank under the Brains for Dementia Research (BDR) initiative. Nancy Allen did immunohistochemistry, all microscopical assessments and data analysis, and helped with paper writing.

Andrew Robinson prepared sections for staining and immunohistochemistry. Julie Snowden helped with statistical advice and clinical data. Yvonne Davidson provided technical support and training. David Mann provided study design, supervision and wrote the paper. “
“Primitive polar spongioblastoma selleckchem was first described by Russell and Cairns in 1947. However, the polar spongioblastoma pattern is often seen in many neuroepithelial tumors, and this category was deleted in the previous World Health Organization (WHO) classification. In 2010, Nagaishi et al. reported on a case involving a neuroepithelial

tumor with the typical histological pattern of polar spongioblastoma and suggested that this tumor might Bioactive Compound Library not be suited to any of the neuroepithelial tumors in the current WHO classification. We report on an autopsy case involving an unclassified high-grade glioma with polar spongioblastoma pattern that was very similar to the case described by Nagaishi et al. A 44-year-old man who presented with a headache exhibited a tumor of the right frontal lobe on MRI. Histological diagnosis of the tumor obtained by gross total resection was high-grade glioma, which was composed of the parallel palisading of spindle tumor cells expressing

GFAP, without microvascular proliferation (MVP) and necrosis. Conventional chemoradiotherapy was performed, but the case was complicated by cerebrospinal fluid (CSF) dissemination that resulted in multiple extraneural metastases through systemic diversionary CSF shunting. Finally, the patient died approximately 13 months after the initial treatment. Both the cerebral and Douglas pouch tumors that were obtained at autopsy were diagnosed as typical glioblastomas, and they were composed of the proliferation of atypical astrocytes with MVP and pseudopalisading necrosis without the formation of rhythmic palisading. Although mafosfamide the histological findings were different from that of the first operation, immunohistochemical and genetic profiles demonstrated almost the same results. This tumor was not classified as a typical glioblastoma by the initial findings, but it had the nature of a glioblastoma. These findings suggest that the tumor might be classified as a new subset of glioblastoma called glioblastoma with polar spongioblastoma pattern. “
“The effect of combustion smoke inhalation on the respiratory system is widely reported but its effects on the central nervous system remain unclear. Here, we aimed to determine the effects of smoke inhalation on the cerebellum and hippocampus which are areas vulnerable to hypoxia injury.