Our results showed that microvascular flaps afford successful combined tissue reconstruction of the foot. © 2011 Wiley-Liss, Inc. Microsurgery, 2011. “
“Reconstruction of bony defects in the surgical management of vertebral osteomyelitis is a challenging endeavor. Our objective is to report the use of intra-abdominal vessels as the recipient vessels for microanastomosis of vascularized bone graft and the use of a spinal cage for fixation. Three patients failed conservative treatment for vertebral osteomyelitis and suffered pathologic fracture. Their treatment consisted of staged posterior irrigation and debridement with segmental fixation, followed by a thoracoabdominal approach multiple-level find more corpectomy. Reconstruction

was performed with a free vascularized fibular graft placed within a custom, expandable cage. The vascularized fibular graft was anastomosed to an intra-abdominal recipient vessel. All patients improved clinically with no neurologic deficits noted. All showed evidence of successful fusion. Free vascularized bone grafts Sotrastaurin continue to be an excellent option for multi-level spinal defects related to osteomyelitis. Intra-abdominal recipient vessels are appropriate recipient vessels, as their diameter, length, and accessibility allow vascularized bone graft reconstruction of vertebral column defects of the thoracolumbar region. These

vessels are also easily accessible and the anastomoses can be performed in the superficial operating incision. Fluorometholone Acetate © 2013 Wiley Periodicals, Inc. Microsurgery 33:560–566, 2013. “
“Background: Animal models and clinical cases of facial allotransplantation have been performed as a single stage procedure. A staged surgery might offer some advantages in selected cases. In this study, a two-stage face transplantation approach was performed on rat and the feasibility and safety were evaluated. Methods: Brown Norway rats were used as donors and Lewis rats as recipients in the allotransplantation

groups. A total of 33 hemiface-scalp transplantations were performed. Syngeneic orthotopic transplantations were performed either in one-stage (one single stage surgery; N = 3), local two-stage [heterothopic transplantation to the neck during the first stage and graft rotation as a pedicled flap to cover the facial defect on postoperative day (POD) 2; N = 3], or distant two-stage approaches (heterothopic transplantation to the groin during the first stage and free graft transfer to the face on postoperative day 2; N = 3). In the allotransplantation groups using the same approaches, 12 received no treatment (N = 4 each subgroup) and 12 received the same tapering dose of cyclosporine (10 to 2 mg/Kg/day; N = 4 each subgroup). Graft survival and the rejection grades were assessed clinically and pathologically. Results: All syngeneic transplants survived for the follow-up period of 180 days. The mean rejection-free survival and total survival of the allograft in the no treatment group was 6 ± 0.3 and 14.3 ± 4.

Therefore we employed physiologically relevant concentrations in our

ex-vivo studies (Fig. 4a). A time–course study demonstrated NET-DNA release between 30 and 70 min (Fig. 5a), and as expected the process was more rapid than mechanisms involving receptor-ligand binding or phagocytosis. Finally, given the in-vivo abundance of taurine within neutrophils and its cytoprotective role in removing HOCl and thus upstream H2O2 by forming taurine chloramines, we investigated MK-8669 cost the effects of adding taurine exogenously to stimulated neutrophils. The taurine effectively prevented both PMA and HOCl-induced NET release, confirming previous studies performed prior to the advent of NET biology, that taurine is capable of rescuing neutrophils from programmed cell death. As discussed previously, whether NET release is followed immediately

by cell death or whether cells remain viable after NET release appears to depend upon the conditions of stimulation, and both outcomes are documented. Although the reports of NETs released from viable cells were not performed using the same stimuli as reported here, the fate of the cells after NET release was not the focus of these studies, and it is recognized that cells may remain viable for a significant period following NET extrusion. The data reported in the current paper demonstrate a pivotal role for HOCl in NET release by peripheral blood neutrophils, identifying for the first time the trigger-point downstream of H2O2. Further studies of this pathway may provide opportunities for therapeutic developments in patients with CGD or in sepsis where AZD3965 research buy NET production may enhance the

resolution of infection or, conversely, may contribute to autoimmune and/or autoinflammatory disease mechanisms. This work was funded by the University of Birmingham. The authors declare that they have no competing interests. “
“Regulatory T cells [Tregs; CD4+CD25+ NADPH-cytochrome-c2 reductase forkhead box protein 3 (FoxP3+)] are subsets of T cells involved in the maintenance of peripheral self-tolerance by actively suppressing the activation and expansion of autoreactive T cells. Signalling through the interleukin-2 receptor (IL-2R) contributes to T cell tolerance by controlling three important aspects of regulatory T cell (Treg) biology. CD25 is the α-chain of the IL-2R that, in concert with the β-chain and γ-chain, constitutes the complete IL-2R. CD25 contributes only to IL-2 binding affinity but not to the recruitment of signalling molecules. However, its importance in the development of a normal immune response is emphasized by the finding that a truncation mutant of CD25 results in an immunodeficiency in humans characterized by an increased susceptibility to viral, bacterial and fungal infections. In 1997, Sharfe et al. described an infant with severe bacterial, viral and fungal infections.

, 2002; Alemán et al., 2007). In the present study, early apoptosis was significantly decreased, whereas the late apoptosis

showed an increasing trend in H37Rv-infected neutrophils. Such accelerated apoptosis of neutrophils after interaction with mycobacteria is essential for the resolution of inflammation (Alemán et al., 2002; Hedlund et al., 2010). Apoptosis is also affected by the secretion of antiapoptotic or pro-apoptotic cytokines. TNF-α is one of Alpelisib the best known pro-apoptotic cytokine. The increased secretion of TNF-α in H37Rv-infected neutrophils suggests its role in inducing late apoptosis and necrosis of these cells. On the other hand, the pro-inflammatory cytokine IFN-γ is antiapoptotic for neutrophils (Colotta et al., 1992) and gets secreted upon stimulation with appropriate agents (Ethuin et al., 2004). However, in this study, only basal expression of IFN-γ was observed under all infected conditions. This indicates that none of the strains were effective in the release of IFN-γ by neutrophils within a short span of 4 h culture. It is reported that TNF-α produced

by infected neutrophils is also involved in the activation of alveolar macrophages in noncontact cultures (Sawant & McMurray, Erlotinib research buy 2007). To determine whether TNF-α produced by infected neutrophils modulates monocyte functions, the expression of CCR5 and CCR7 on monocytes was studied. Usually, the expression of CCR7 by peripheral monocytes is low or negative, and little upregulation happens after differentiation

into macrophages. Similarly, in this study, the expression of CCR7 dipyridamole was low and not significant on monocytes stimulated with BCG- and Mw-infected NU sups. However, increased expression of CCR7 was observed with H37Rv-infected Nu sup. This might be due to increased secretion of TNF-α in H37Rv-infected Nu sup; however, this requires further experimental proof. On the other hand, CCR5 expression on peripheral monocytes is usually greater, and accordingly, its upregulation was observed under all infected conditions in this study. Although the exact mechanism for this upregulation is not known, it is sure to be neutrophil-mediated. In our previous report, we did not find any increase in the levels of MIP-1α (chemokine ligand of CCR5) at early time point of 3 h after infection of neutrophils with H37Rv (Pokkali et al., 2009). This basal level of chemokine may not be sufficient to bind to CCR5 and downregulate its expression level; instead, it may act as a trigger for the monocytes to upregulate CCR5 expression. In another study, when mononuclear cells were stimulated with MTB antigen, CCR5 expression on monocytes was increased, but CCR7 was hardly detectable (Arias et al., 2006). Interestingly, we observed increase in the expression of both the receptors on monocytes, supporting the fact that both CCR5- and CCR7-mediated monocyte signaling functions occur with the help of neutrophils.

[124] Myeloid cells have also been shown to regulate susceptibility to EAE following activation of type I NKT cells by αGalCer.[134] Hence, depletion of immunosuppressive myeloid-derived suppressor cells from the spleen results in the loss of αGalCer-induced protection from EAE.

These reports suggest that activation of NKT cell subsets Roscovitine clinical trial in different tissues may not only lead to their interaction with professional APCs but also with other immune regulatory cells, including myeloid-derived suppressor cells and Treg cells, and that they can cooperate to provide protection from autoimmune pathology. In this review, we have attempted to identify key outstanding issues related to the role of NKT cell subsets in health and disease, and how some of these issues may be addressed experimentally and clinically. Based on current evidence, we have proposed a hypothesis that states that while type I NKT cells have pathogenic and protective roles in autoimmune disease susceptibility, type II NKT cells possess mainly a protective role. We have discussed how new experimental mouse models coupled with the application of novel techniques, namely intravital cellular imaging in vivo and mass cytometry, may test this hypothesis and also

provide important insights into the role of NKT–DC interactions and cytokine/chemokine secretion profiles in determining the outcome of health versus disease. As the CD1d-dependent

antigen recognition pathway is highly conserved from mice to humans, several key features of NKT cell Small molecule library manufacturer subsets are shared between them. Although most studies in mice have analysed NKT cells from the thymus, spleen or liver, the systemic results of their manipulation indicate that follow-up clinical studies are warranted. Therefore, discoveries in experimental models can be translated into the clinical setting,[1, 128] and allow the application of murine studies to humans. Fortunately, type II NKT cells occur more frequently than type I NKT cells Decitabine in humans, which facilitates their further characterization using appropriate lipid ligands. A detailed characterization of type II NKT cells and their ligands in humans is important for their appropriate manipulation in disease conditions. Phase I/II clinical trials of the anti-tumour effects of human type I NKT cells stimulated by αGalCer have yielded promising results.[129, 130, 71, 131] Other analogues of αGalCer that skew conventional CD4+ T-cell responses towards either a Th1- or a Th2-like profile remain to be tested in similar trials. In the near future, it may be possible to differentially activate or inhibit type I and type II NKT cells for the development of novel immunotherapeutic protocols in the treatment and prevention of autoimmune disease.

Results  When compared to the

post-partum samples, significant pregnancy-related changes in IFNγ, TNFα, VEGF, GCSF, Eotaxin, and MCP-1 expression were observed. These changes have significant immunologic effects in vivo and in culture. Conclusion  Pregnancy-associated changes to steady state serum cytokines may have important immunologic consequence. “
“We studied early NK-cell recovery in 29 allografted patients undergoing different lymphoreductive regimens. Already at 2 wk after graft take, the number of NK cells had Ferroptosis phosphorylation reached (supra)normal levels but NK-cell subsets were skewed. The number of CD56dimCD16bright NK cells was low and correlated strongly with the level of hematopoiesis, whereas the number of the more abundant NK cells expressing high levels of CD56 did not. Post-transplant CD56bright NK cells (ptCD56bright) differed from CD56bright NK cells in normal controls (CD56bright) in being HLA-DR- and perforin-positive, CCR7−, CD27−, CD127− and mostly

c-kit−. CD56bright from normal controls stimulated by IL-15 in vitro (NKIL-15) acquired all the characteristics FK228 chemical structure distinguishing CD56bright from ptCD56bright. IL-2 exerted similar effects. Moreover, when cultured without cytokines, ptCD56bright, CD56bright and NKIL-15 responded similarly by upregulating CD127 and c-kit but not CCR7. IL-12 stimulated IFN-γ production in ptCD56bright, whereas CD56bright responded only to IL-12 plus IL-15. Hence, ptCD56bright have all the features of cytokine-stimulated CD56bright. Because only patients with low numbers of T cells had high numbers of ptCD56bright, we conclude that ptCD56bright are activated CD56bright that expand while competing with T cells for the elevated post-transplant level of IL-15. In humans, most lymphocytes without Molecular motor rearranged antigen-receptors express CD56 and are referred to as NK cells. Accordingly, they can be identified on the basis of a CD3−CD56+ phenotype 1–3, which excludes the subpopulation of T cells that coexpress CD56. However, this long-established definition of NK cells may be inadequate because CD3−CD56+ lymphocytes

are heterogeneous and capable of exerting various effector functions other than killing cells with altered expression of self-MHC. Furthermore, many CD3−CD56+ lymphocytes do not lyse NK-cell targets when tested ex vivo and only acquire lytic activity after in vitro stimulation with cytokines. In fact, the large granular CD3−CD56+ lymphocytes with “natural” cytotoxicity that express low levels of CD56 (CD56dim) and high levels of the Fcγ-receptor type III (CD16) 1–4 represent only a minority of all of the CD3−CD56+ lymphocytes in the body 5, 6. CD56dim that provide first-line defense against viruses 7, 8 make out 90% of NK cells in human peripheral blood. They express killer immunoglobulin-like receptors (KIR), contain perforin and granzymes and are considered to be end-stage cytotoxic effector cells. A substantial percentage of CD56dim lacks CD94 4.

TAMs with ionized calcium-binding adaptor molecule 1 (Iba1) positivity and morphology of activated, non-phagocytic microglia increased within and around the tumors in malignant gliomas and anaplastic astrocytomas. The Iba1-positive TAMs of

the tumor core were significantly more activated than Iba1-positive microglia of non-neoplastic brain tissue in intraparenchymal anaplastic oligodendrogliomas. Iba1 expression showed a significant positive correlation to Ki-67 expression in all the gliomas. Most TAMs showed no or little expression against CD68, CD163 or CD204, although CD204-positive TAMs were observed in necrosis as well as in the proliferating vascular wall. In conclusion, S-100β-v-erbB TG rats may serve as a useful animal find more model for further

analysis of TAMs in terms of tumor cell proliferation, microvascular proliferation and phagocytosis, and as a tool for therapeutic use in malignant gliomas, although it should be noted that the polarization of TAMs toward the M2 phenotype remains unclear. “
“Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used in various industries and the field of dentistry. The consequent increase in BPA exposure among humans has led us to some concerns regarding the potential deleterious effects on reproduction and brain development. The emphasis of this review is on the effects of prenatal and lactational Atezolizumab clinical trial exposure to low doses of BPA on brain development in mice. We demonstrated that prenatal exposure to BPA affected fetal murine neocortical development by accelerating neuronal differentiation/migration during the early embryonic stage, which

was associated with up- and down-regulation of the genes critical for brain development, including the basic helix-loop-helix transcription factors. In the adult mice brains, both abnormal neocortical architecture and abnormal corticothalamic projections persisted in the group exposed to the BPA. Functionally, BPA exposure disturbed murine behavior, accompanied with a disrupted neurotransmitter system, including monoamines, in the postnatal development period and in adult Adenylyl cyclase mice. We also demonstrated that epigenetic alterations in promoter-associated CpG islands might underlie some of the effects on brain development after exposure to BPA. “
“S. J. Connelly, E. B. Mukaetova-Ladinska, Z. Abdul-All, J. Alves da Silva, C. Brayne, W. G. Honer and D. M. A. Mann (2011) Neuropathology and Applied Neurobiology37, 366–380 Synaptic changes in frontotemporal lobar degeneration: correlation with MAPT haplotype and APOE genotype Aims: This immunohistochemical study quantified synaptic changes (synaptophysin and SNAP-25) in the frontal lobe of subjects with frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD), and related these to APOE genotype and MAPT haplotype.

1− donor cells nor to a significant conversion into Foxp3+ WT Treg cells (Fig. 2B, right panel). These results

could be confirmed in a different experimental system by employing luciferase-expressing Treg cells 36 with a WT TCR repertoire. Monitoring Foxp3-specific light emission clearly showed similar WT Treg-cell expansion in OT-II TCR-Tg hosts over time (Fig. 2C). In addition, the same effect of efficient competition with the less diverse endogenous host Treg cells was observed after transfer into a different strain of TCR-Tg hosts, namely OT-I (Fig. 2C). Furthermore, WT donor Alvelestat supplier Treg-cell frequency in TCR-Tg hosts correlated to the input dose (Fig. 2D) and their expansion was associated with higher proliferation rates and an activated phenotype (Fig. 2E and F). Re-analysis of recovered donor Treg cells 2 months after transfer revealed a reduced but still highly diverse TCR repertoire when compared with similar numbers of the control group (Supporting Information Fig. 2). Therefore, sustained survival and expansion was not restricted to a small number of clones but included a broad set of donor Treg cells. This suggests that TCR diversity and continuous self-antigen recognition control the total size of the peripheral Treg-cell pool independently of homeostatic factors such as IL-2. Of note, exogenous administration of recombinant IL-2 increased Treg-cell proliferation and absolute numbers in both

WT and TCR-Tg mice (Supporting Information Fig. 3). Taken together, these adoptive transfer experiments revealed a hitherto unappreciated role for TCR diversity in Treg-cell homeostasis and imply that find more Cyclooxygenase (COX) it is probably a combination of TCR specificity and TCR-independent factors that determine on the one hand the competitive/homeostatic fitness of Treg cells and on the other hand the total pool/niche size. In principle, endogenous rearrangements in TCR-Tg mice were able to produce any potential TCR chain combination and thus there were no distinct gaps in their Treg-cell repertoire. However, we still observed a few qualitative differences on the Treg-cell population level. Jα-usage of the analyzed Vα8 family sequences in

Treg cells from TCR-Tg mice showed an increased proportion of the elements TRAJ5*01 and TRAJ34*02 (Supporting Information Fig. 4), while Jα-element usage was consistent in independent experiments for both types of Treg cells (Supporting Information Fig. 4). It is likely that this biased Jα-usage reflects preferential selection of Tcra rearrangements that can efficiently pair with the clonotypic Tcrb chain. Furthermore, productive VJ rearrangements in TCR-Tg mice included on average more non-templated N-nucleotides compared with WT Treg cells (6.679±0.079 versus 5.89±0.050 N-nucleotides; p<0.0001). Also, we found lower isoelectric point (pI) values of pH 9.289±0.029 for the Treg cells from TCR-Tg mice versus pH 9.473±0.021 (p<0.0001) in WT.

In crustaceans the enzymes of proPO system have been detected in LGH and SGH. Several authors reported degranulation from numerous SGH and LGH in shrimp LO. Moreover, using histochemical procedures, Shao et al. (20) and Anggraeny and Owens (21) detected PO activity in LO and LOS, respectively. However, melanization is absent in the filtering process and LOS formation. Since α2-macroglobulin has been involved in the regulation of the proPO system (35), its presence could help explain the absence of melanization in immune reactions

that occur in the LO. According to Rusaini and Owens (9) the LOS may be disposed of through the antennal gland. The coelomosac podocytes might play a role in removing waste substances. The immunolabeling

of podocytes of the antennal gland with the MAB 40E10 could indicate a possible role of podocytes removing LOS debris. selleck chemical We can not rule out the possibility that this cross-reactivity was the result of an antigenic relationship between SGH, and other cells involved in clearance such as the podocytes in the antennal gland and fixed phagocytes in the heart (5). Phagocytic reserve heart cells are involved in endocytosis, and the positive signal for α2-macroglobulin could indicate a process of internalization selleck kinase inhibitor of complexes α2-macroglobulin – protease by these cells. Moreover, hemocyte subpopulations exhibited specific tissue tropism. Immunostaining for HH hemocytes was detected in the connective tissues close to the digestive system, while a positive signal to GH was observed in connective tissues in the oral region. In conclusion, our results indicate that

the three hemocyte subpopulations SGH, LGH, and genuine HH have an important role in clearance processes that occur in the LO. Two molecules, peneidins and α2-macroglobulin, that are involved in pathogen destruction and phagocytosis, are released from hemocytes in the tubule walls of LO. WSSV is filtered in the LO tubule walls being possibly agglutinated, opsonised and engulfed by hemocytes (likely SGH and HH), which become part of LOS. This work was supported by the Escuela Superior Politécnica del Litoral (ESPOL), Guayaquil, Ecuador and the Belgian Technical Cooperation (BTC), Belgium, through a Master grant to Martha Maldonado. None of the authors has any conflicts of interest associated with this study. “
“Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune selleck screening library disorder caused by mutations in the autoimmune regulator (AIRE) gene. High-titre autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in approximately 7% of APS1 patients, with immunoreactivity to pituitary tissue frequently described. Using APS1 patient serum to immunoscreen a pituitary cDNA expression library, testis specific, 10 (TSGA10) was isolated. Immunoreactivity against TSGA10 was detected in 5/99 (5.05%) patients with APS1, but also in 5/135 (3.

However, as shown in Fig. 5B, the intensity and position of the bands of ODN1668 at incubation time 0 were not affected by the see more change in the ratio of DNase I-treated ODN1720 to ODN1668. These results

suggest that the DNase I-treated DNA does not bind to ODN1668. Therefore, other mechanism than the nucleotide binding to ODN would be involved in the DNase I-treated DNA-mediated increase. Therefore, other mechanisms than these should be involved in the increased cytokine production by DNase I-treated DNA. In recent reports, the conformational changes of both TLR9 and CpG DNA were shown to be an important process for the activation of the TLR9 pathway. CpG DNA allosterically changes the TLR9 protein to

the dimer accessible to CpG motif and MyD88, which results in the activation of NF-κB and cytokine release 30. In addition, TLR9 recognition requires an intramolecular or intermolecular double-stranded DNA region at the position of the CpG motif and single-stranded DNA region at the 5′ end 31, 32. Conformational changes in TLR9 would not be involved in the DNase I-treated ODN1720, because the TNF-α production induced by A-type or B-type CpG ODN, other TLR9 ligands, was not increased by DNase I-treated DNA. These ligand-dependent effects of DNase I-treated ODN1720 could be explained by assuming that DNase I-treated ODN1720 has some direct effects on ODN1668 and pCMV-Luc, both of which are the only two PO DNA used in the present study. One possible LY294002 cell line mechanism

is that DNase I-treated DNA alters the conformations of PO-CpG ODN into forms with a high ability to interact with TLR9 protein. This hypothesis is also compatible with the results of an absence of significant effects of DNase I-treated ODN on the non-CpG lipoplex-induced TNF-α production (Fig. 2A), which was mediated by receptors other than TLR9 18, 19. Glutathione peroxidase Further studies are needed to identify the mechanism for the increase in the cytokine release by DNase I-treated DNA. It is reported that DNase I-deficient mice and humans have anti-DNA antibody with high frequency and are prone to SLE 33, 34. Moreover, the DNase I activity was lower in SLE patients than in the control group 35. In the sera of DNase I-deficient individuals, an increasing amount of undegraded self-DNA containing CpG motifs can be an exacerbating factor of CpG-dependent immune response. For the purpose of treatment for lupus nephritis, in which the deposition of self-DNA/anti-DNA antibody complex in glomeruli is thought to be crucial for the disease pathogenesis, recombinant human DNase I was intravenously administered into the patients. Although serum hydrolytic activity of recombinant human DNase I was achieved after administration, there were no significant changes in serum inflammatory cytokines, including TNF-α and IL-6 36.

On the contrary,

carbachol- and EFS-induced contractile-responses in old WHHL-MI rabbits showed significantly lower responses compared to control rabbits. The maximum contractile responses to carbachol and EFS in young and old WHHL-MI rabbits and control rabbits are presented Alectinib order in Table 3. The bladder specimens were also stained immunohistochemically in the presence of mouse monoclonal S-100 protein antibodies and sheep polyclonal calcitonin gene-related peptide (CGRP) antibodies. All stained nerve fibers were counted in at least five high-power field, then the mean nerve density score (MNDS) was calculated, according to the method described by Van Poppel et al.24 The results showed that S-100 protein-positive neurons mainly in smooth muscle layer, and number of the neurons gradually decreased with age, with a significantly lower number in WHHL-MI rabbits compared to the control rabbits. CGRP-positive neurons were observed mainly in urothelium. CGRP-positive neurons had significantly larger MNDS in the tissues of young and old WHHL-MI rabbits compared to control rabbits (Table 4). Azadzoi et al.22,23 studied a rabbit model developed to show moderate bladder ischemia

(MBI) and severe bladder ischemia (SBI), and reported that MBI produced bladder overactivity and increased contractile response to carbachol and EFS stimulation with moderate fibrosis in the bladder wall, whereas SBI showed very weak contraction and decreased response to stimulation.

SBI also showed severe fibrosis. It is interesting that the ischemic bladder models showed almost the same results as the WHHL-MI rabbit Ulixertinib mouse model. In the present study, detrusor overactivity and increased contractile responses to carbachol and EFS were observed in young WHHL-MI rabbits. In addition, young WHHL-MI rabbits showed a significant decrease in S-100 protein-positive neurons. As enough S-100 protein-positive neurons include motor neurons, detrusor overactivity of young WHHL-MI rabbits could be considered as a condition of denervation-induced hypersensitivity. Although the mechanism of denervation is not fully understood, Ca2+-dependent neutral protease calpain may be activated by ischemia and result in proteolysis of neuronal membranes.18 On the other hand, CGRP-positive neurons emerged to increase in WHHL-MI rabbits. CGRP is one of the predominant excitatory neurotransmitters in mediating sensory perception, and is an important nociceptive marker.25 CGRP has a major role in mediating hypersensitivity in many systems, including the lower urinary tract.26 Therefore, the increased CGRP-positive neurons in this study may contribute to the activation of bladder afferents. In addition, nerve growth factor (NGF) seems to control, at least partly, survival and outgrowth of CGRP-positive neurons through its tyrosine kinase receptor A, and increase in NGF and CGRP-positive neurons have a strong relationship with detrusor overactivity in spinal cord-injured rats.