Cord Inflammation Research Articles

Inhibitory effects of alprazolam on the development of acute experimental autoimmune encephalomyelitis in stressed rats

The progression and development of multiple sclerosis (MS) has long been hypothesized to be associated with stress. Benzodiazepines have been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on their effects on MS, or experimental autoimmune encephalomyelitis (EAE), a model for human MS. We designed experiments conducted to ascertain whether alprazolam could modify the clinical, histological and neuroendocrine manifestations of acute EAE in Lewis rats exposed to a chronic auditory stressor. EAE was induced by injection of an emulsion of MBP and complete Freund's adjuvant containing Mycobacterium tuberculosis H37Ra. Stress application and treatment with drugs (placebo or alprazolam) were initiated 5 days before inoculation and continued daily for the duration of the experiment (days 14 or 34 postinoculation).Our results show significant increases in the severity of neurological signs, the histological lesions of the spinal cord (inflammation), and the corticosterone plasmatic levels in stressed rats compared to those non-stressed ones. Treatment with alprazolam reversed the adverse effects of stress. These findings could have clinical implications in patients suffering from MS treated with benzodiazepines, so besides the psychopharmacological properties of alprazolam against stress, it has beneficial consequences on EAE.

Olprinone Attenuates the Acute Inflammatory Response and Apoptosis after Spinal Cord Trauma in Mice

BackgroundOlprinone hydrochloride is a newly developed compound that selectively inhibits PDE type III and is characterized by several properties, including positive inotropic effects, peripheral vasodilatory effects, and a bronchodilator effect. In clinical settings, olprinone is commonly used to treat congestive cardiac failure, due to its inotropic and vasodilating effects. The mechanism of these cardiac effects is attributed to increased cellular concentrations of cAMP. The aim of the present study was to evaluate the pharmacological action of olprinone on the secondary damage in experimental spinal cord injury (SCI) in mice.Methodology/Principal FindingsTraumatic SCI is characterized by an immediate, irreversible loss of tissue at the lesion site, as well as a secondary expansion of tissue damage over time. Although secondary injury should be preventable, no effective treatment options currently exist for patients with SCI. Spinal cord trauma was induced in mice by the application of vascular clips (force of 24 g) to the dura via a four-level T5–T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, apoptosis, and locomotor disturbance. Olprinone treatment (0.2 mg/kg, i.p.) 1 and 6 h after the SCI significantly reduced: (1) the degree of spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (myeloperoxidase activity), (3) nitrotyrosine formation, (4) pro-inflammatory cytokines, (5) NF-κB expression, (6) p-ERK1/2 and p38 expression and (7) apoptosis (TUNEL staining, FAS ligand, Bax and Bcl-2 expression). Moreover, olprinone significantly ameliorated the recovery of hind-limb function (evaluated by motor recovery score).Conclusions/SignificanceTaken together, our results clearly demonstrate that olprinone treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.

EAE mediated by a non‐IFN‐γ/non‐IL‐17 pathway

Previous studies have shown that EAE can be elicited by the adoptive transfer of either IFN-γ-producing (Th1) or IL-17-producing (Th17) myelin-specific CD4(+) T-cell lines. Paradoxically, mice deficient in either IFN-γ or IL-17 remain susceptible to EAE following immunization with myelin antigens in CFA. These observations raise questions about the redundancy of IFN-γ and IL-17 in autoimmune demyelinating disease mediated by a diverse, polyclonal population of autoreactive T cells. In this study, we show that an atypical form of EAE, induced in C57BL/6 mice by the adoptive transfer of IFN-γ-deficient effector T cells, required IL-17 signaling for the development of brainstem infiltrates. In contrast, classical EAE, characterized by predominant spinal cord inflammation, occurred in the combined absence of IFN-γ and IL-17 signaling, but was dependent on GM-CSF and CXCR2. Our findings contribute to a growing body of data, indicating that individual cytokines vary in their importance across different models of CNS autoimmunity.

Performance of a repetitive task by aged rats leads to median neuropathy and spinal cord inflammation with associated sensorimotor declines

Epidemiological studies have demonstrated a relationship between advancing age and susceptibility to risk factors for median neuropathies and musculoskeletal disorders. In this study, we determined if performance of a voluntary reaching task by aged rats induced sensorimotor declines, median nerve dysfunction and increased inflammatory cytokines in peripheral nerves, muscle and spinal cord neurons. Aged (14 mon) rats were trained for 15 min/day for 4 weeks to learn a high repetition, low force (HRLF) task (19 reaches/min; 15% maximum pulling force). Aged task rats performed the task for 2 h/day, 3 days/wk, for 12 weeks (until they were 18 mon of age). No behavioral changes were detected in normal controls (NC) or food-restricted controls (FR C) as they aged. However, grip strength declined in HRLF rats in weeks 6–12 (P<0.01 each) and 12-week trained-only rats (TR; P<0.05), compared to NC. Mechanical hypersensitivity was present in weeks 9 and 12 HRLF reach limb forepaws (P<0.01 and P<0.05, respectively), and 12-week HRLF support limb forepaws (P<0.01) and hindpaws (P=0.03), compared to NC. By week 12, median nerve conduction velocity declined 23%, bilaterally, in HRLF (P<0.001 each), and 13% in TR (P<0.05), compared to NC. Tumor necrosis factor alpha (TNFα) increased in 12-week HRLF muscle (P=0.005), median nerve (P<0.01), and neurons in superficial lamina of HRLF cervical spinal cords (P<0.01), compared to NC. interleukin 1 beta (IL1β) also increased in superficial lamina neurons (P<0.01). Loss of grip strength was correlated with median nerve conduction slowing (r=0.70) as well as increased nerve and muscle TNFα (r=−0.38 and r=−0.41, respectively); decrease in forepaw withdrawal thresholds was correlated with median nerve conduction slowing (r=0.81), increased nerve TNFα (r=−0.59), and increased TNFα and IL1β in neurons in spinal cord dorsal horns (r=−0.52 and r=−0.47, respectively). Thus, aged rats performing a repetitive task exhibited sensorimotor declines that were associated with decreased median nerve conduction, and increased pro-inflammatory cytokines in the median nerve and cervical spinal cord neurons.

The alternative and terminal pathways of complement mediate post-traumatic spinal cord inflammation and injury

The alternative and terminal pathways of complement mediate post-traumatic spinal cord inflammation and injury

Fetal Inflammatory Response is Often Present at Early Stages of Intra-amniotic Infection, and its Distribution along Cord is Variable

This study investigates the hypotheses that (1) the fetal inflammatory response to intra-amniotic infection can occur in early stages of maternal inflammatory response and (2) a difference in early cord inflammation exists at different sites in the cord. Placentas accessioned in our department over a 4-year period with a differential in umbilical vessel inflammation between proximal and distal sections were evaluated for cord inflammation using a 0 to 4 graded scale. Cases were also evaluated for acute chorionic vasculitis and extent of maternal inflammatory response. Of 5566 placentas, 1004 (18%) had some degree of cord inflammation; 120 (12%) had a differential in inflammation between the 2 cord sites. Greater cord inflammation was divided almost equally between proximal (59) and distal (61) sections. Twenty-two cases had 1 or both arteries involved in 1 cord section only. The proximal section had the greater degree of inflammation in 21 (95%) of these cases. Early or no maternal inflammatory response was seen in 63 of 120 cases (52%). Acute chorionic vasculitis was identified in 57 of 106 cases (54%) with at least 2 chorionic vessels present. Fetal inflammatory response can be seen in early amniotic infection, occasionally without finding maternal inflammatory response. The absence of differences in cord vein inflammation depending on cord site and the finding that arteritis occurs close to the placental cord insertion site suggest that cord vessel blood flow dynamics play a role in neutrophil margination. At least 2 cord sections representing proximal and distal sites are recommended to exclude fetal inflammatory response.

Role of Early Surgical Decompression of the Intradural Space After Cervical Spinal Cord Injury in an Animal Model

The role of decompressing the intradural space through a durotomy as a treatment option for acute traumatic cervical spinal cord injury has not been explored in an animal model, to our knowledge. We sought to determine the role of durotomy and duraplasty in the treatment of acute cervical spinal cord injury and its effects on inflammation, scar formation, and functional recovery. Seventy-two adult female Sprague-Dawley rats were assigned to three groups: contusion injury alone, contusion injury with a decompressive durotomy, and contusion injury with a decompressive durotomy followed by placement of a dural allograft. A mild (200-kdyn [2-N]) contusive injury was delivered to the exposed spinal cord at C5. The injured segment was reexposed four hours after injury, and a durotomy with decompression was performed. When a dural allograft was used it was affixed to the surrounding intact dura with use of a fibrin sealant. The Grip Strength Meter was used to assess forelimb function. Animals were killed at two and four weeks, and immunohistochemical analysis was performed to assess scar formation, inflammatory cell infiltration, and lesional volume. Immunohistochemical analysis revealed increased scar formation, cavitation, and inflammatory response in the animals treated only with a decompressive durotomy. Relative to the group with a contusion injury alone, the animals treated with a durotomy followed by a dural allograft had decreased cavitation and scar formation. Lesional volume measurements showed a significantly increased cavitation size at four weeks in both the contusion-only (mean and standard deviation, 12.6 +/- 0.5 mm(3)) and durotomy-only (15.1 +/- 1 mm(3)) groups relative to the animals that had received a dural allograft following durotomy (6.8 +/- 1.4 mm(3)). Functional recovery after acute cervical spinal cord injury was better in animals treated with decompression of the intradural space and placement of a dural allograft than it was in animals treated with decompression alone. These functional data correlated directly with histological evidence of a decrease in spinal cord cavitation, inflammation, and scar formation.

Immunization with pVAXhsp65 Decreases Inflammation and Modulates Immune Response in Experimental Encephalomyelitis

Background: A DNA vaccine (pVAXhsp65) containing the gene of a heat-shock protein (hsp65) from Mycobacterium leprae showed high immunogenicity and protective efficacy against tuberculosis in BALB/c mice. A possible deleterious effect related to autoimmunity needed to be tested because hsp65 is highly homologous to the correspondent mammalian protein. In this investigation we tested the effect of a previous immunization with DNAhsp65 in the development of experimental autoimmune encephalomyelitis (EAE), a rat model of multiple sclerosis. Methods: Female Lewis rats were immunized with 3 pVAXhsp65 doses by intramuscular route. Fifteen days after the last DNA dose the animals were evaluated for specific immunity or submitted to induction of EAE. Animals were evaluated daily for weight loss and clinical score, and euthanized during the recovery phase to assess the immune response and inflammatory infiltration at the central nervous system. Results: Immunization with pVAXhsp65 induced a specific immune response characterized by production of IgG_2b anti-hsp65 antibodies and IFN-γ secretion. Previous immunization with pVAXhsp65 did not change EAE clinical manifestations (weight and clinical score). However, the vaccine clearly decreased brain and lumbar spinal cord inflammation. In addition, it downmodulated IFN-γ and IL-10 production by peripheral lymphoid organs. Conclusion: Our data demonstrated that this vaccine does not trigger a deleterious effect on EAE development and also points to a potential protective effect.

Evidence for the role of PPAR‐β/δ in the development of spinal cord injury

Evidence suggests a biological role for peroxisome proliferator activated receptor (PPAR)‐β/δ in the pathogenesis of a number of diseases. The aim of the present study was to evaluate the contribution of PPAR‐β/δ in the secondary damage following experimental spinal cord injury (SCI) in mice. Spinal cord trauma was induced by the application of vascular clips to the dura via a four‐level T5–T8 laminectomy. SCI resulted in severe trauma characterized by oedema, neutrophil infiltration, production of inflammatory mediators, tissue damage, and apoptosis. The high affinity PPAR‐β/δ agonist GW0742 (0.3 mg/kg, i.p.) 1 and 6 h after the SCI significantly reduced: (1) the degree of spinal cord inflammation and tissue injury, (2) neutrophil infiltration, (3) nitrotyrosine formation, (4) pro‐inflammmaory cytokines, (5) NF‐κB activation, (6) iNOS expression and (6) apoptosis (TUNEL staining, FasL, Bax and Bcl‐2 expression). Moreover, GW0742 significantly ameliorated the recovery of locomotory function (evaluated by motor score). In order to elucidate whether the protective effects of GW0742 are related to activation of the PPAR‐β/δ, we investigated the function of PPAR‐β/δ antagonist, GSK0660, on the protective effects of GW0742. GSK0660 (1 mg/kg i.p. 30 min prior to GW0742)significantly blunted the protective effect of the PPAR‐β/δ agonist. Our results demonstrate that GW0742 treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.

Evidence for the Role of Peroxisome Proliferator-Activated Receptor-β/δ in the Development of Spinal Cord Injury

Several lines of evidence suggest a biological role for peroxisome proliferator-activated receptor (PPAR)-beta/delta in the pathogenesis many diseases. The aim of the present study was to evaluate the contribution of PPAR-beta/delta in the secondary damage in experimental spinal cord injury (SCI) in mice. To this purpose, we used 4-[[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methylphenoxy]acetic acid (GW0742), a high-affinity PPAR-beta/delta agonist. Spinal cord trauma was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, production of inflammatory mediators, tissue damage, and apoptosis. GW0742 treatment (0.3 mg kg(-1) i.p.) 1 and 6 h after the SCI significantly reduced 1) the degree of spinal cord inflammation and tissue injury (histological score), 2) neutrophil infiltration (myeloperoxidase activity), 3) nitrotyrosine formation, 4) proinflammatory cytokines expression, 5) nuclear factor-kappaB activation, 6) inducible nitric-oxide synthase expression, and 6) apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, FasL, Bax, and Bcl-2 expression). Moreover, GW0742 significantly ameliorated the recovery of limb function (evaluated by motor recovery score). To elucidate whether the protective effects of GW0742 are related to activation of the PPAR-beta/delta receptor, we also investigated the effect of PPAR-beta/delta antagonist methyl 3-({[2-(methoxy)-4 phenyl]amino}sulfonyl)-2-thiophenecarboxylate (GSK0660) on the protective effects of GW0742. GSK0660 (1 mg/kg i.p. 30 min before treatment with GW0742) significantly blocked the effect of the PPAR-beta/delta agonist and thus abolished the protective effect. Our results clearly demonstrate that GW0742 treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.

The clinical course of idiopathic acute transverse myelitis in patients from Rio de Janeiro

The aim of this study was to describe the demographic, clinical and laboratory features of idiopathic acute transverse myelitis (IATM). Patients with non-compressive ATM receiving care at Hospital da Lagoa, Rio de Janeiro (Brazil) between 2000 and 2008 were selected. Of the 70 cases of acute myelopathies, the idiopathic form was identified in 41 following exclusion of the cases associated with systemic lupus erythematosus (n = 1), Sjogren's syndrome (n = 1), herpes zoster (n = 1), cytomegalovirus in an HIV-positive patient (n = 1), Schistosoma mansoni (n = 1), actinic myelitis (n = 1), infectious myelitis of unknown etiology (n = 2) and those that, following the first attack of myelitis, converted to NMO (n = 19) or to clinically defined MS (n = 2). Of the 41 cases of IATM, the majority of patients were female (68.3%) and white (65.9%). Median age at first myelitis was 37.0 +/- 11.8 years. Over a median observation time of 36 months, 39.0% of patients remained monophasic, while recurrences occurred in 61.0% of cases. The number of ATM/patient ranged from one to seven. Among the recurrent cases the median time between the first and the second ATM was 12 months (range 1-150 months).The first myelitis was characterized mainly by partial myelitis with motor and sensorial dysfunction (63.4%). Complete and severe myelitis occurred more frequently among monophasic patients and partial myelitis with moderate dysfunction at onset in recurrent cases; however, over the long-term, dysfunction and disability were mild in both groups. Serial spine MRI confirmed spinal cord inflammation in 92.0% of cases and extensive spinal cord lesion was identified in 61.0%. Brain MRI was normal or not suggestive of MS in 94.4% of cases. CSF showed pleocytosis in 41.2%, increased IgG index in 24.0% and oligoclonal bands in 38.0% of 34 patients tested. Abnormal visual evoked potentials occurred in 11.5% of 26 patients. Positivity for anti-AQP4 was found in 23.5% of the 17 cases tested, suggesting limited forms of NMO. This study suggests some new aspects of the clinical course of IATM such as the high conversion rate to NMO, the predominance of women and a higher frequency of recurrent forms.

Liver X receptor agonist treatment regulates inflammatory response after spinal cord trauma

Liver X receptor alpha (LXRalpha) and LXRbeta are members of the nuclear receptor superfamily of ligand-activated transcription factors. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy in mice. Treatment with T0901317, 1 and 6 h after the SCI, significantly decreased (i) the degree of spinal cord inflammation and tissue injury (histological score); (ii) neutrophil infiltration (myeloperoxidase activity); (iii) inducible nitric oxide synthase expression; (iv) nitrotyrosine, lipid peroxidation, and poly-ADP-ribose formation; (v) pro-inflammatory cytokines expression; (vi) nuclear factor-kappa B activation; and (vii) apoptosis (terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, FAS ligand, Bax, and Bcl-2 expression). Moreover, T0901317 significantly ameliorated the loss of limb function (evaluated by motor recovery score). These data suggest that LXR ligand may be useful in the treatment of inflammation associated with SCI.

Fibromyalgia and the Fallacy of Pain from Nowhere: Figure 1.

To the Editor: The controversies surrounding fibromyalgia (FM) and the absolute mess the diagnostic label of “fibromyalgia” has created were recently reviewed1–3. Unfortunately, not one of the articles addresses the fundamental problem that exists within the construct of the FM diagnosis: the fallacy of pain from nowhere. While the unifying theme across the 3 articles is that FM is a dead-end diagnosis begging for definition and context, they fail to address the fact that absolutely nobody has actually identified the source of the pain that patients suffer. Clearly, abnormalities in pain-processing with central sensitization to external pain stimulation have been well documented in FM, and it has been widely accepted in standard reviews and textbooks, without argument, that it is from here that FM pain arises4–8. However, there is absolutely no evidence that central sensitization actually causes spontaneous, non-externally stimulated pain. The implication that the pain of FM arises out of a central sensitization syndrome, despite the knowledge that central sensitization is a modification response to actively induced pain and not a source of pain itself9,10, is a true failure of medical science. Central sensitization does not cause pain. It simply modulates pain from a defined, active pain source. Further, there is absolutely no evidence that primary FM is a true central pain syndrome with pain originating from abnormalities of the central nervous system, such as are seen in brain and spinal cord vascular lesions, traumatic injury, tumors, inflammation, and infection; multiple sclerosis; syringomyelia and syringobulbia; epilepsy; and Parkinson’s disease11. … Address correspondence to Dr. Sarkozi. E-mail: jsarkozi{at}fmpolypain.com

Filiform-like enlargement of spinal central canal on MRI

Objective Filiform-like enlarged central canal without reasonable cause detected by magnetic resonance image(MRI) was studied and reported. Method 30 patients with an intramedullary filiform-like cavity(1～2 mm in diameter) were identified through MRI in our hospital from 2003 to 2005. Main causes of hydromyelia, such as anatomical factors of Chiari malformation, hydrocephalus, spinal cord malformation,tumor,trauma, and inflammation, were excluded among these patients. Results All the 30 patients had spine malformation, and most of them (21 of 30) were diagnosed as adolescent idiopathic scoliosis(AIS). The slightly clinical manifestations were identified but no obviously neurological damage and no changes were found in follow up, which meant no additional medical interference was needed. Conclusions The filiform-like cavity intramedullary in MRI image can be identified as the central of the spinal cord with slightly enlargement;however, this enlargement of spinal central canal was different from hydromyelia and no treatments were needed. Key words: Syringomyelia; Magnetic resonance imaging; Scoliosis

Adipose-Derived Mesenchymal Stem Cells Ameliorate Chronic Experimental Autoimmune Encephalomyelitis

Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for neurological autoimmune diseases; previous studies have shown that treatment with bone marrow-derived MSCs induces immune modulation and reduces disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we show that intravenous administration of adipose-derived MSCs (ASCs) before disease onset significantly reduces the severity of EAE by immune modulation and decreases spinal cord inflammation and demyelination. ASCs preferentially home into lymphoid organs but also migrates inside the central nervous system (CNS). Most importantly, administration of ASCs in chronic established EAE significantly ameliorates the disease course and reduces both demyelination and axonal loss, and induces a Th2-type cytokine shift in T cells. Interestingly, a relevant subset of ASCs expresses activated alpha 4 integrins and adheres to inflamed brain venules in intravital microscopy experiments. Bioluminescence imaging shows that alpha 4 integrins control ASC accumulation in inflamed CNS. Importantly, we found that ASC cultures produce basic fibroblast growth factor, brain-derived growth factor, and platelet-derived growth factor-AB. Moreover, ASC infiltration within demyelinated areas is accompanied by increased number of endogenous oligodendrocyte progenitors. In conclusion, we show that ASCs have clear therapeutic potential by a bimodal mechanism, by suppressing the autoimmune response in early phases of disease as well as by inducing local neuroregeneration by endogenous progenitors in animals with established disease. Overall, our data suggest that ASCs represent a valuable tool for stem cell-based therapy in chronic inflammatory diseases of the CNS.

BENEFICIAL EFFECTS OF ETHYL PYRUVATE IN A MOUSE MODEL OF SPINAL CORD INJURY

The aim of the present study was to evaluate in a mouse model of spinal cord injury (SCI) the effect of the treatment with ethyl pyruvate (EP). Spinal cord injury was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy in mice. Treatment with EP (75, 25, or 8.5 mg/kg) 1 and 6 h after the SCI significantly decreased (a) the degree of spinal cord inflammation and tissue injury (histological score), (b) neutrophil infiltration (myeloperoxidase activity), (c) nitrotyrosine formation and iNOS expression, (d) proinflammatory cytokines expression, (e) nuclear factor kappaB activation, (f) extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase phosphorylation, and (g) apoptosis (TUNEL staining, Fas ligand, Bax, and Bcl-2 expression). Moreover, EP (75, 25, or 8.5 mg/kg) significantly ameliorated in a dose-dependent manner the loss of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that EP treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.

Presyrinx in children with Chiari malformations

Goh et al.1 report that only two out of six children with presyrinx and Chiari malformation had symptoms related to myelopathy. Although classically considered a neurosurgical condition, neurologists should also be aware of presyrinx and consider its possible paucisymptomatic picture and coexistence with a number of spinal cord medical disorders. Goh et al. also alluded to, but did not report the clinical detail of, five additional cases with an alleged presyrinx associated with spinal cord inflammation or tumors. We previously reported a patient with an MRI-documented presyrinx associated with myelitis.2 The suspect of a presyrinx was prompted …

Perinatal Correlates of Ureaplasma urealyticum in Placenta Parenchyma of Singleton Pregnancies That End Before 28 Weeks of Gestation

The purpose of this work was to examine the relationship between Ureaplasma urealyticum in the placenta and perinatal outcomes in extreme preterm deliveries and to explore the influence of bacteria coinfection on perinatal outcomes in U urealyticum-positive placentas. Under sterile conditions, a piece of chorion from 866 singleton deliveries before 28 weeks' gestation was obtained and flash frozen. The tissue was later homogenized and cultured for Ureaplasma and bacteria. Placentas were also examined histologically. Maternal and neonatal data were obtained prospectively. Each infant had 3 sets of cranial ultrasound scans between days 1 to 4, 5 to 14, and between day 15 and 40th week postconceptional age. Cranial ultrasound findings were by consensus of 2 or 2 of 3 sonologists. U urealyticum was recovered from 6% and bacteria from 47%; 47% of placentas had no bacteria detectable. Sixty-seven percent of Ureaplasma-positive placentas also harbored bacteria. Placentas that harbored U urealyticum only were more likely than sterile placentas to be associated with a higher prevalence of preterm labor and preterm premature rupture of membranes, as well as umbilical cord, fetal vessel, membrane, and parenchymal inflammation and to predict intraventricular hemorrhage and echolucent brain lesions. Placentas that harbored U urealyticum only were similar to placentas that harbored bacteria only. Recovery of U urealyticum and bacteria from same placenta did not enhance the differences between placentas with U urealyticum alone and sterile placentas. Recovery of U urealyticum only was not associated with a higher risk of death before day 7 of life. The presence of U urealyticum in placental parenchyma before 28 weeks is associated with increased risk of preterm labor and delivery, higher risk of fetal and maternal inflammation, and increased risk of intraventricular hemorrhage and echolucent brain lesions but not of early neonatal death.

Treatment with green tea extract attenuates secondary inflammatory response in an experimental model of spinal cord trauma

In this study, we evaluated the effect of green tea extract (that was administered 25 mg/kg intraperitoneal at 1 and 6 h after injury) in experimental animal model of spinal cord injury. The spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5–T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterised by oedema, neutrophilic infiltration and apoptosis. Also, immunohistochemical examination demonstrated a marked increase in immune reactivity for nitrotyrosine. All parameters of inflammation were attenuated by green tea extract. The degree of spinal cord inflammation, nitrotyrosine, poli (ADP-ribosio) synthetase (PARS) and neutrophilic infiltration was markedly reduced. Green tea extract significantly ameliorated the recovery of limb function. Values shown are mean ± SE mean of ten mice for each group. *p < 0.01 versus sham, °p < 0.01 versus spinal cord injury. Taken together, our results clearly demonstrate that green tea extract treatment ameliorates spinal cord injury oxidative stress.

GLYCYRRHIZIN REDUCES SECONDARY INFLAMMATORY PROCESS AFTER SPINAL CORD COMPRESSION INJURY IN MICE

Glycyrrhizin, a major active constituent of liquorice root (Glycyrrhiza glabra), has a free radical scavenging property, and its effects were evaluated on an animal model of spinal cord injury (SCI) induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, tissue damage, and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated dUTP-biotin end labeling staining, Bax, and Bcl-2 expression). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine, iNOS, and poly(adenosine diphosphate-ribose) in the spinal cord tissue. Additionally, we demonstrate that these inflammatory events were associated with the activation of nuclear factor-kappaB. In contrast, the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) nitrotyrosine and poly(adenosine diphosphate [ADP] ribose) formation, (3) iNOS expression, (4) nuclear factor-kappaB activation, and (5) apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP-biotin end labeling, Bax, and Bcl-2) was markedly reduced in spinal cord tissue obtained from mice treated with glycyrrhizin extract (10 mg/kg, i.p., 30 min before and 1 and 6 h after SCI). In a separate set of experiments, we have clearly demonstrated that glycyrrhizin extract treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with glycyrrhizin extract reduces the development of inflammation and tissue injury events associated with spinal cord trauma.