Biomedical subjects

P F Stahel

Publications and source records attributed to P F Stahel.

At least 19 recordsLinked to original sources

PubMed2007

Immunohistochemical characterization of Fas (CD95) and Fas Ligand (FasL/CD95L) expression in the injured brain: relationship with neuronal cell death and inflammatory mediators.

Traumatic brain injury causes progressive tissue atrophy and consequent neurological dysfunction, resulting from neuronal cell death in both animal models and patients. Fas (CD95) and Fas ligand (FasL/CD95L) are important mediators of apoptosis. However, little is known about the relationship between Fas and FasL and neuronal cell death in mice lacking the genes for inflammatory cytokines. In the present study, double tumor necrosis factor/lymphotoxin-alpha knockout (-/-) and interleukin-6-/- mice were subjected to closed head injury (CHI) and sacrificed at 24 hours or 7 days post-injury. Consecutive brain sections were evaluated for Fas and FasL expression, in situ DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling; TUNEL), morphologic characteristics of apoptotic cell death and leukocyte infiltration. A peak incidence of TUNEL positive cells was found in the injured cortex at 24 hours which remained slightly elevated at 7 days and coincided with maximum Fas expression. FasL was only moderately increased at 24 hours and showed maximum expression at 7 days. A few TUNEL positive cells were also found in the ipsilateral hippocampus at 24 hours. Apoptotic, TUNEL positive cells mostly co-localized with neurons and Fas and FasL immunoreactivity. The amount of accumulated polymorphonuclear leukocytes and CD11b positive cells was maximal in the injured hemispheres at 24 hours. We show strong evidence that Fas and FasL might be involved in neuronal apoptosis after CHI. Furthermore, Fas and FasL upregulation seems to be independent of neuroinflammation since no differences were found between cytokine-/- and wild-type mice.

Animals↗

PubMed2005

Erythropoietin is neuroprotective, improves functional recovery, and reduces neuronal apoptosis and inflammation in a rodent model of experimental closed head injury.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young people in industrialized countries. Although various anti-inflammatory and antiapoptotic modalities have shown neuroprotective effects in experimental models of TBI, to date, no specific pharmacological agent aimed at blocking the progression of secondary brain damage has been approved for clinical use. Erythropoietin (Epo) belongs to the cytokine superfamily and has traditionally been viewed as a hematopoiesis-regulating hormone. The newly discovered neuroprotective properties of Epo lead us to investigate its effect in TBI in a mouse model of closed head injury. Recombinant human erythropoietin (rhEpo) was injected at 1 and 24 h after TBI, and the effect on recovery of motor and cognitive functions, tissue inflammation, axonal degeneration, and apoptosis was evaluated up to 14 days. Motor deficits were lower, cognitive function was restored faster, and less apoptotic neurons and caspase-3 expression were found in rhEpo-treated as compared with vehicle-treated animals (P<0.05). Axons at the trauma area in rhEpo-treated mice were relatively well preserved compared with controls (shown by their density; P<0.01). Immunohistochemical analysis revealed a reduced activation of glial cells by staining for GFAP and complement receptor type 3 (CD11b/CD18) in the injured hemisphere of Epo- vs. vehicle-treated animals. We propose that further studies on Epo in TBI should be conducted in order to consider it as a novel therapy for TBI.

Animals↗

PubMed2005

Ultrasonography as a reliable diagnostic tool in old quadriceps tendon ruptures: a prospective multicentre study.

Quadriceps tendon rupture is an uncommon injury. In the majority of cases, predispositions as recurrent microtrauma or degenerative changes are present. The diagnosis of acute quadriceps tendon ruptures can usually be made by clinical examination. Ultrasonography has been shown as a reliable, inexpensive and easily available diagnostic tool to confirm the diagnosis. In this study, we evaluated the clinical value of ultrasonography for establishing diagnosis of old quadriceps tendon ruptures. In the prospective time period of 6 years (01/1998-12/2003), the delayed diagnosis of quadriceps tendon rupture was established in six patients with seven cases of old ruptures (one bilateral rupture). The mean age was 50.2 (SD+/-16.9) years in one woman and five men. The mean interval from trauma until diagnosis was 15.2 (SD+/-7.1; range 8-24) weeks. In all cases, ultrasonography represented a reliable and sensitive tool for establishing diagnosis of old quadriceps tendon rupture. We therefore recommend the use of ultrasonography in the diagnostic work up of cases with knee trauma and potential involvement of tendon injuries.

Adult↗

PubMed2005

[Current concepts of polytrauma management: from ATLS to "damage control"].

In recent years, the implementation of standardized protocols for polytrauma management has led to a significant improvement in trauma care as well as to a decrease in post-traumatic morbidity and mortality. As such, the "Advanced Trauma Life Support" (ATLS) protocol of the American College of Surgeons for the acute management of severely injured patients has been established as a gold standard in most European countries since the 1990s. Continuative concepts to the ATLS program include the "Definitive Surgical Trauma Care" (DSTC) algorithm and the concept of "damage control" surgery for polytraumatized patients with immediate life-threatening injuries. These phase-oriented therapeutic strategies appraise the injured patient of the whole extent of the sustained injuries and are in sharp contrast to previous modalities of "early total care" which advocate immediate definitive surgical intervention. The approach of "damage control" surgery takes into account the influence of systemic post-traumatic inflammatory and metabolic reactions of the organism and is aimed at reducing both the primary and the secondary, delayed, mortality in severely injured patients. The present paper provides an overview of the current state of management algorithms for polytrauma patients, with a focus on the standard concepts of ATLS and "damage control".

Adult↗

PubMed2005

[Traumatic brain injury: impact on timing and modality of fracture care].

Traumatic brain injury (TBI) represents the major "killing factor" after trauma in young individuals. Those patients who survive the initial injury are highly susceptible to secondary insults to the injured brain which are mainly caused by hypotension and/or hypoxia in the early resuscitative period. Furthermore, a potent inflammatory cascade is initiated within the injured brain which leads to the development of brain edema and delayed neuronal cell death. This profound endogenous neuroinflammatory response after TBI, which is phylogenetically aimed at repairing lesioned tissue and defending the brain from invading pathogens, is in large part responsible for the extent of secondary brain damage and adverse outcome. Thus, the optimal management of the multiply injured patient, based on a thorough understanding of the pathophysiological alterations after TBI, should avoid an iatrogenic "second hit" which may be devastating to the injured brain. The standard approach of "early total care" for isolated fractures should be strictly avoided in brain-injured patients in favor of an "orthopedic damage control" concept with temporary external fixation of long bone fractures and priority given to early transfer to intensive care. The present review provides an up-to-date overview on the neuroinflammatory pathophysiology of brain injury and its implications for an optimized concept of fracture care in TBI patients.

Adult↗

PubMed2005

[Emergency management of thoracic trauma].

Thoracic injuries are a major cause of mortality during the "golden hour" of trauma. Many patients with chest trauma die after reaching the hospital. Less than 10% of all blunt thoracic injuries require a thoracotomy, and many potentially life-threatening conditions can be relieved by simple procedures, such as chest tube insertion.Thus, many cases of traumatic deaths due to chest injury may be prevented by prompt diagnosis and a standardized therapeutic approach in the emergency room. A high index of suspicion for lethal injury patterns, based on the mechanism of trauma and the clinical presentation, is a crucial prerequisite for an adequate initial assessment and management of patients with chest trauma. The worldwide implementation of standardized diagnostic and therapeutic guidelines, such as the "Advanced Trauma Life Support" (ATLS) protocol, has led to a significant reduction of early deaths attributed to thoracic injuries.

Adult↗

PubMed2004

[The role of whole body spiral CT in the primary work-up of polytrauma patients--comparison with conventional radiography and abdominal sonography].

PURPOSE: To evaluate the role of routine "whole body spiral CT"in the primary work-up of polytrauma patients for injuries of the thorax, abdomen and spine, and to compare the results with those of conventional radiography of the chest and spine and abdominal ultrasound. MATERIALS AND METHODS: Fifty consecutive polytrauma patients underwent contrast-enhanced single slice spiral CT (5 mm collimation) from the vertex to the floor of the pelvis as part of the primary work-up after emergency room admission. Overlapping high resolution sections and sagittal reformations of the spine were obtained. Reports of additional chest radiographs (n=43), abdominal ultrasound examinations(n = 47) and spine radiographs (n = 36) performed in the emergency room were available for retrospective comparison. The "final diagnoses," which served as the standard of reference, were taken from the patients' records using all information that be-came available until discharge or death, such as findings from further imaging, surgery and autopsy. RESULTS: CT showed 109(97%) of 112 thoracic and abdominal soft-tissue injuries. Relevant injuries missed were an early splenic laceration and an early pelvic hematoma, both of which became clinically apparent several hours later. There were 4 false positive CT findings. Conventional chest radiography demonstrated only 20% of thoracic and sonography 22% of abdominal injuries. Chest radiography and sonography produced 2 false-positive findings each. CT showed 66 (87%) of 76 vertebral fractures including all 19 unstable ones.CT missed 5 anterior vertebral body and 5 spinous/transverse process fractures. Conventional radiography found 71 % of vertebral fractures including only 50 % of the unstable ones. CONCLUSION: Routine performance of whole body spiral CT as part of the primary work-up of polytrauma patients provides a fast and comprehensive survey and detects almost all soft tissue injuries of the chest and abdomen. It is clearly superior to chest radiography and abdominal sonography. All spinal injuries relevant for the acute management were also seen on CT, but not on conventional radiography.

Abdominal Injuries↗

PubMed2003

Predictive value of complement activation fragments C3a and sC5b-9 for development of severe disease in patients with acute pancreatitis.

BACKGROUND: Complement activation has been shown to occur in patients with acute pancreatitis. However, the diagnostic potential of complement activation products in plasma for predicting severe disease remains unclear to date. METHODS: The daily levels of the complement anaphylatoxin C3a and the soluble terminal complement complex sC5b-9 were determined by ELISA in plasma of patients with mild (n = 16) or severe (n = 14) acute pancreatitis during the first week after onset of symptoms, and in healthy control subjects (n = 14). RESULTS: Both C3a and sC5b-9 were significantly elevated during the first 7 days in plasma of patients with severe acute pancreatitis (C3a: 459.3 +/- 407.5 ng/mL (mean +/- s); sC5b-9: 617.9 +/- 297.7 ng/mL), as compared to patients with mild disease (C3a: 172 +/- 149.5 ng/mL; sC5b-9: 306.7 +/- 167.3 ng/mL) or controls (C3a: 102.3 +/- 19.7 ng/mL; sC5b-9: 40.64 +/- 19.7 ng/mL; P < 0.001, repeated measures ANOVA). The analysis of both parameters in combination during the first week after onset of symptoms revealed a high sensitivity (0.93) and specificity (0.88) as well as high negative and positive predictive values (0.93 and 0.87, respectively) with an odds ratio of 91.0 for the development of pancreatic necrosis (P < 0.0001, Fisher exact test). CONCLUSION: In patients with acute pancreatitis, the plasma levels of complement C3a and sC5b-9 measured daily during the first week after onset of symptoms represent highly specific and sensitive parameters for the prediction of severe acute pancreatitis.

Acute Disease↗

PubMed2001

Regulation of chemokines and chemokine receptors after experimental closed head injury.

The expression of the chemokines macrophage inflammatory protein (MIP)-2 and MIP-1alpha and of their receptors CXCR2 and CCR5 was assessed in wild type (WT) and TNF/lymphotoxin-alpha knockout (TNF/LT-alpha-/-) mice subjected to closed head injury (CHI). At 4 h after trauma intracerebral MIP-2 and MIP-1alpha levels were increased in both groups with MIP-2 concentrations being significantly higher in WT than in TNF/LT-alpha-/- animals (p < 0.05). Thereafter, MIP-2 production declined rapidly, whereas MIP-1alpha remained elevated for 7 days. Expression of CXCR2 was confined to astrocytes and increased dramatically within 24 h in both mouse types. Contrarily, CCR5 expression remained constitutively low and was mainly localized to microglia. These results show that after CHI, chemokines and their receptors are regulated differentially and with independent kinetics.

Animals↗

PubMed2001

Pancreatic infection in severe pancreatitis: the role of fungus and multiresistant organisms.

HYPOTHESIS: Recent controlled clinical studies suggest a positive effect of early antibiotic treatment on late morbidity and mortality in severe acute pancreatitis. However, widespread use of antibiotics may lead to an increased number of fungal infections and multiresistant bacteria, thereby worsening the outcome of the disease. DESIGN: Single-center prospective study. SETTING: University hospital, gastrointestinal surgical service. PATIENTS: One hundred three patients with necrotizing pancreatitis seen consecutively in our service. INTERVENTIONS: In addition to standard treatment, patients with proven necrotizing pancreatitis received a prophylactic intravenous antibiotic treatment. Pancreatic infection was regarded as an indication for surgery. MAIN OUTCOME MEASURES: Pancreatic infection, microbiological findings, drug resistance, fungal infections. RESULTS: Thirty-three patients (32%) had infected necrosis. Gram-negative organisms were isolated from 19 patients (58%), Gram-positive organisms were isolated from 18 patients (55%), fungal organisms were isolated from 8 patients (24%), and multiresistant organisms were isolated from 3 patients (9%). In 7 patients (21%), the organisms cultured from the pancreatic tissue were resistant to the antibiotics given in for prophylaxis. Infection with multiresistant organisms or organisms resistant to the antibiotic used for prophylaxis, but not with fungal infection or Gram-positive or Gram-negative infection, was correlated with a negative outcome. CONCLUSIONS: Fungal infection under adequate treatment is not associated with a negative outcome. The occurrence of multiresistant organisms seems to be a rare finding (3 of 103 patients). Antibiotic prophylaxis is effective in preventing infection in necrotizing pancreatitis, but optimal choice and duration of administration of the antibiotic agent(s) need to be carefully determined to avoid the sequelae of multiresistant organisms.

Adult↗

PubMed2001

1 alpha,25-Dihydroxycholecalciferol reduces rejection and improves survival in rat liver allografts.

Vitamin D(3) affects the immuno response and improves experimental autoimmune diseases. We investigated the effect of 1,25-dihydroxycholecalciferol (1,25[OH](2)D(3)) Rocaltrol as a single immunosuppressive agent and in combination with low-dose cyclosporin A (CsA) in vascularized liver allografts in rats in a high-responder strain combination (ACI-->Lewis). Recipients were placed on a low-calcium diet 7 days before transplantation and were treated with 0.1 or 1 microg/kg/d 1,25(OH)(2)D(3) intraperitoneally beginning 3 days before transplantation. Treatment combining 1,25(OH)(2)D(3) with CsA (2 mg/kg/d) was also tested. Graft function and survival, histologic rejection, and concentrations of interleukin (IL)-2, -4, -10, and -12 in serum and in grafts were measured. 1,25(OH)(2)D(3) increased allograft survival in a dose-dependent manner when compared with controls (P <.05 for both groups). Serum bilirubin, aspartate transaminase (AST), and lactate dehydrogenase (LDH) activities were significantly lower in 1,25(OH)(2)D(3)-treated animals. Vitamin D reduced the concentration of IL-2 and IL-12 in serum and in grafts, and increased IL-4 and IL-10 in the grafts. The rejection activity index 10 days after transplantation was significantly lower in low- and high-dose 1,25(OH)(2)D(3)-treated rats compared with vehicle-treated controls (P <.0001 for both groups). The combination of either low-dose or high-dose vitamin D(3) and CsA prolonged graft survival when compared with low-dose CsA only (P <.05 for both groups). After 3 weeks, hypercalcemia developed in high-dose 1,25(OH)(2)D(3)-treated rats. It is concluded that 1,25(OH)(2)D(3) prolongs survival of liver allografts in rats by decreasing the severity of acute rejection. Analogues of vitamin D with fewer hypercalcemic effects may have potential as immunosuppressive drugs in liver transplantation.

Animals↗

PubMed2001

Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury.

It has become evident in recent years that intracranial inflammation after traumatic brain injury (TBI) is, at least in part, mediated by activation of the complement system. However, most conclusions have been drawn from experimental studies, and the intrathecal activation of the complement cascade after TBI has not yet been demonstrated in humans. In the present study, we analyzed the levels of the soluble terminal complement complex sC5b-9 by ELISA in ventricular cerebrospinal fluid (CSF) of patients with severe TBI (n = 11) for up to 10 days after trauma. The mean sC5b-9 levels in CSF were significantly elevated in 10 of 11 TBI patients compared to control CSF from subjects without trauma or inflammatory neurological disease (n = 12; p < 0.001). In some patients, the maximal sC5b-9 concentrations were up to 1,800-fold higher than in control CSF. The analysis of the extent of posttraumatic blood-brain barrier (BBB) dysfunction, as determined by CSF/serum albumin quotient (Q(A)), revealed that patients with a moderate to severe BBB impairment (mean Q(A) > 0.01) had significantly higher intrathecal sC5b-9 levels as compared to patients with normal BBB function (mean Q(A) < 0.007; p < 0.0001). In addition, a significant correlation between the individual daily Q(A) values and the corresponding sC5b-9 CSF levels was detected in 8 of 11 patients (r = 0.72-0.998; p < 0.05). These data demonstrate for the first time that terminal pathway complement activation occurs after head injury and suggest a possible pathophysiological role of complement with regard to posttraumatic BBB dysfunction.

Adolescent↗

PubMed2001

Role of cerebral inflammation after traumatic brain injury: a revisited concept.

Neuroinflammation occuring after traumatic brain injury (TBI) is a complex phenomenon comprising distinct cellular and molecular events involving the injured as well as the healthy cerebral tissue. Although immunoactivation only represents a one of the many cascades initiated in the pathophysiology of TBI, the exact function of each mediator, activated cell types or pathophysiological mechanism, needs to be further elucidated. It is widely accepted that inflammatory events display dual and opposing roles promoting, on the one hand, the repair of the injured tissue and, on the other hand, causing additional brain damage mediated by the numerous neurotoxic substances released. Most of the data supporting these hypotheses derive from experimental work based on both animal models and cultured neuronal cells. More recently, evidence has been provided that a complete elimination of selected inflammatory mediators is rather detrimental as shown by the attenuation of neurological recovery. However, there are conflicting results reported on this issue which strongly depend on the experimental setting used. The history of immunoactivation in neurotrauma is the subject of this review article, giving particular emphasis to the comparison of clinical versus experimental studies performed over the last 10 years. These results also are evaluated with respect to other neuropathologies, which are years ahead as compared to the research in TBI. The possible reciprocal influence of peripheral and intrathecal activation of the immune system will also be discussed. To conclude, the future directions of research in the field of neurotrauma is considered.

Animals↗

PubMed2000

Intracerebral complement C5a receptor (CD88) expression is regulated by TNF and lymphotoxin-alpha following closed head injury in mice.

The anaphylatoxin C5a is a potent mediator of inflammation in the CNS. We analyzed the intracerebral expression of the C5a receptor (C5aR) in a model of closed head injury (CHI) in mice. Up-regulation of C5aR mRNA and protein expression was observed mainly on neurons in sham-operated and head-injured wild-type mice at 24 h. In contrast, in TNF/lymphotoxin-alpha knockout mice, the intracerebral C5aR expression remained at low constitutive levels after sham operation, whereas it strongly increased in response to trauma between 24 and 72 h. Interestingly, by 7 days after CHI, the intrathecal C5aR expression was clearly attenuated in the knockout animals. These data show that the posttraumatic neuronal expression of the C5aR is, at least in part, regulated by TNF and lymphotoxin-alpha at 7 days after trauma.

Animals↗

PubMed2000

[Traumatic paraplegia: surgical measures].

Reduction and fixation of unstable spine injuries in patients with neurological deficit are the prerequisites for early rehabilitation. Diagnostic procedures and surgery in patients with para-/tetraplegia must be performed urgently to avoid further neurological damage and ensure recovery. In parallel administration, high-dose steroids are initiated immediately after admission. In general, unstable spine fractures are reduced in a closed or open manner and stabilised. Bony fragments occluding the spinal channel are removed and, if necessary, the anterior column is reconstructed. Unstable fractures of the cervical spine are operated on either from the back and/or anteriorly, although the techniques used in the upper cervical spine are quite different from those used in the lower cervical spine. Instabilities of the thoraco-lumbar junction are reduced and stabilised via a dorsal and/or anterior-lateral approach (transthoracic or retroperitoneal). Exact preoperative planning is necessary due to the proximity of large vessels and organs, as well as the narrow space for positioning of the implants. With early operative stabilisation of the spine paretic/paralysed patients can be mobilised immediately and personal care is facilitated. In this article the operative techniques are described on the basis of examples chosen from 606 patients treated at the Division of Trauma Surgery, University Hospital of Zurich from 1992 to 1997. 119 patients (19%) were diagnosed with incomplete/complete para-/tetraplegia and 51 with various degrees of neurological deficit.

Decompression, Surgical↗

PubMed2000

Experimental closed head injury: analysis of neurological outcome, blood-brain barrier dysfunction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines.

Cytokines are important mediators of intracranial inflammation following traumatic brain injury (TBI). In the present study, the neurological impairment and mortality, blood-brain barrier (BBB) function, intracranial polymorphonuclear leukocyte (PMN) accumulation, and posttraumatic neuronal cell death were monitored in mice lacking the genes for tumor necrosis factor (TNF)/lymphotoxin-alpha (LT-alpha) (TNF/LT-alpha-/-) and interleukin-6 (IL-6) and in wild-type (WT) littermates subjected to experimental closed head injury (total n = 107). The posttraumatic mortality was significantly increased in TNF/LT-alpha-/- mice (40%; P < 0.02) compared with WT animals (10%). The IL-6-/- mice also showed a higher mortality (17%) than their WT littermates (5.6%), but the difference was not statistically significant (P > 0.05). The neurological severity score was similar among all groups from 1 to 72 hours after trauma, whereas at 7 days, the TNF/LT-alpha-/- mice showed a tendency toward better neurological recovery than their WT littermates. Interestingly, neither the degree of BBB dysfunction nor the number of infiltrating PMNs in the injured hemisphere was different between WT and cytokine-deficient mice. Furthermore, the analysis of brain sections by in situ DNA nick end labeling (TUNEL histochemistry) at 24 hours and 7 days after head injury revealed a similar extent of posttraumatic intracranial cell death in all animals. These results show that the pathophysiological sequelae of TBI are not significantly altered in mice lacking the genes for the proinflammatory cytokines TNF, LT-alpha, and IL-6. Nevertheless, the increased posttraumatic mortality in TNF/LT-alpha-deficient mice suggests a protective effect of these cytokines by mechanisms that have not been elucidated yet.

Animals↗

PubMed2000

Traumatic brain injury elevates the Alzheimer's amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury.

The increased risk for Alzheimer's Disease (AD) associated with traumatic brain injury (TBI) suggests that environmental insults may influence the development of this age-related dementia. Recently, we have shown that the levels of the beta-amyloid peptide (A beta 1-42) increase in the cerebrospinal fluid (CSF) of patients after severe brain injury and remain elevated for some time after the initial event. The relationships of elevated A beta with markers of blood-brain barrier (BBB) disruption, inflammation, and nerve cell or axonal injury were evaluated in CSF samples taken daily from TBI patients. This analysis reveals that the rise in A beta 1-42 is best correlated with possible markers of neuronal or axonal injury, the cytoskeletal protein tau, neuron-specific enolase (NSE), and apolipoprotein E (ApoE). Similar or better correlations were observed between A beta 1-40 and the three aforementioned markers. These results imply that the degree of brain injury may play a decisive role in determining the levels of A beta 1-42 and A beta 1-40 in the CSF of TBI patients. Inflammation and alterations in BBB may play lesser, but nonetheless significant, roles in determining the A beta level in CSF after brain injury.

Acute-Phase Proteins↗

PubMed1999

Receptor for the C3a anaphylatoxin is expressed by neurons and glial cells.

Little is known about the expression of the receptor for complement anaphylatoxin C3a (C3aR) in the central nervous system (CNS). In this study, we provide the first evidence that neurons are the predominant cell type expressing C3aR in the normal CNS. By using in situ hybridization (ISH) and immunohistochemistry, we found that C3aR is constitutively expressed at high levels in cortical and hippocampal neurons as well as in Purkinje cells. Moreover, we showed that primary culture of human astrocytes and microglia express the C3aR mRNA as assessed by RT-PCR. In situ hybridization performed on rat primary astrocytes confirmed the RT-PCR result demonstrating C3aR expression by astrocytes. In experimental allergic encephalitis (EAE), C3aR expression was elevated on microglia, infiltrating monocyte-macrophage cells and a few astrocytes, whereas neuronal expression remained unchanged during the course of the disease. These data demonstrate that the C3aR is expressed primarily by neurons in the normal CNS and that its neuronal expression is not dramatically upregulated under inflammation. This is in contrast to the increased neuronal expression of the C5aR in several inflammatory CNS conditions. The high constitutive expression of the C3aR by neurons suggests this receptor may play an important role in normal physiological conditions in the CNS.

Anaphylatoxins↗