Changes in hemodynamics and tissue oxygenation saturation in the brain and skeletal muscle induced by speech therapy - a near-infrared spectroscopy study

Arts speech therapy (AST) is a therapeutic method within complementary medicine and has been practiced for decades for various medical conditions. It comprises listening and the recitation of different forms of speech exercises under the guidance of a licensed speech therapist. The aim of our study was to noninvasively investigate whether different types of recitation influence hemodynamics and oxygenation in the brain and skeletal leg muscle using near-infrared spectroscopy (NIRS). Seventeen healthy volunteers (eight men and nine women, mean age ± standard deviation 35.6 ± 12.7 years) were enrolled in the study. Each subject was measured three times on different days with the different types of recitation: hexameter, alliteration, and prose verse. Before, during, and after recitation, relative concentration changes of oxyhemoglobin (Δ[O2Hb]), deoxyhemoglobin (Δ[HHb]), total hemoglobin (Δ[tHb]), and tissue oxygenation saturation (StO2) were measured in the brain and skeletal leg muscle using a NIRS device. The study was performed with a randomized crossover design. Significant concentration changes were found during recitation of all verses, with mainly a decrease in Δ[O2Hb] and ΔStO2 in the brain, and an increase in Δ[O2Hb] and Δ[tHb] in the leg muscle during recitation. After the recitations, significant changes were mainly increases of Δ[HHb] and Δ[tHb] in the calf muscle. The Mayer wave spectral power (MWP) was also significantly affected, i.e., mainly the MWP of the Δ[O2Hb] and Δ[tHb] increased in the brain during recitation of hexameter and prose verse. The changes in MWP were also significantly different between hexameter and alliteration, and hexameter and prose. Possible physiological explanations for these changes are discussed. A probable reason is a different effect of recitations on the sympathetic nervous system. In conclusion, these changes show that AST has relevant effects on the hemodynamics and oxygenation of the brain and muscle.

Glycoprotein D of bovine herpesvirus 5 (BoHV-5) confers an extended host range to BoHV-1 but does not contribute to invasion of the brain

Bovine herpesvirus 1 (BoHV-1) and BoHV-5 are closely related pathogens of cattle, but only BoHV-5 is considered a neuropathogen. We engineered intertypic gD exchange mutants with BoHV-1 and BoHV-5 backbones in order to address their in vitro and in vivo host ranges, with particular interest in invasion of the brain. The new viruses replicated in cell culture with similar dynamics and to titers comparable to those of their wild-type parents. However, gD of BoHV-5 (gD5) was able to interact with a surprisingly broad range of nectins. In vivo, gD5 provided a virulent phenotype to BoHV-1 in AR129 mice, featuring a high incidence of neurological symptoms and early onset of disease. However, only virus with the BoHV-5 backbone, independent of the gD type, was detected in the brain by immunohistology. Thus, gD of BoHV-5 confers an extended cellular host range to BoHV-1 and may be considered a virulence factor but does not contribute to the invasion of the brain.

Effect Of Yolk Testosterone On Gonadal Testosterone And Aromatase Activity In The Pre-Optic Area Of The Brain In Male Domestic C

Maternal effects are a mother¿s non-genetic contributions to development that alter phenotypic traits in offspring. Maternal effects can take the form of prenatal allocation of resources, such as the deposition of androgens into egg yolks. For example, elevated yolk testosterone increases male sexual behaviors such as copulation solicitation and courtship displays in some avian species, in addition to aggressive behaviors like pecks and intimidating postures towards same-sex competitors. However, the mechanism connecting in ovo testosterone exposure with changes in sexual and aggressive behaviors has yet to be elucidated. While testosterone released by the gonads is important in the activation of sexual behaviors, it must undergo conversion to estrogen by the enzyme aromatase in the pre-optic area (POA) of the avian brain for full expression of sexual activity. POA aromatase is also necessary for the activation of aggressive behaviors in male birds. This experiment tested the hypothesis that elevated yolk testosterone leads to changes in POA aromatase activity and levels of gonadal testosterone, as these two endocrine parameters may mediate the effect of yolk testosterone on the frequency of sexual and aggressive behaviors. The effect of elevated yolk testosterone on gonadal testosterone levels and aromatase activity in the POA of 3-day-old domestic chickens Gallus gallus domesticus was investigated. Unincubated eggs were injected with either 10 ng testosterone in 50 ¿L sesame oil (¿T chicks¿) or 50 ¿L sesame oil (¿C chicks¿). At 3 days post-hatch, gonadal testosterone content was measured after steroid extraction using an EIA, and aromatase activity in the POA was quantified by measuring the production of tritiated water from [1ß-3H]-androstenedione. I predicted that gonadal testosterone levels and brain aromatase activity would be higher in T chicks, however found no difference between treatments. Though juvenile T production peaks at 3 days post-hatch, it is possible that the reproductive systems, including the testes and POA, are not fully developed at this time.

The neurovascular unit as a selective barrier to polymorphonuclear granulocyte (PMN) infiltration into the brain after ischemic injury

The migration of polymorphonuclear granulocytes (PMN) into the brain parenchyma and release of their abundant proteases are considered the main causes of neuronal cell death and reperfusion injury following ischemia. Yet, therapies targeting PMN egress have been largely ineffective. To address this discrepancy we investigated the temporo-spatial localization of PMNs early after transient ischemia in a murine transient middle cerebral artery occlusion (tMCAO) model and human stroke specimens. Using specific markers that distinguish PMN (Ly6G) from monocytes/macrophages (Ly6C) and that define the cellular and basement membrane boundaries of the neurovascular unit (NVU), histology and confocal microscopy revealed that virtually no PMNs entered the infarcted CNS parenchyma. Regardless of tMCAO duration, PMNs were mainly restricted to luminal surfaces or perivascular spaces of cerebral vessels. Vascular PMN accumulation showed no spatial correlation with increased vessel permeability, enhanced expression of endothelial cell adhesion molecules, platelet aggregation or release of neutrophil extracellular traps. Live cell imaging studies confirmed that oxygen and glucose deprivation followed by reoxygenation fail to induce PMN migration across a brain endothelial monolayer under flow conditions in vitro. The absence of PMN infiltration in infarcted brain tissues was corroborated in 25 human stroke specimens collected at early time points after infarction. Our observations identify the NVU rather than the brain parenchyma as the site of PMN action after CNS ischemia and suggest reappraisal of targets for therapies to reduce reperfusion injury after stroke.

Doxycycline reduces mortality and injury to the brain and cochlea in experimental pneumococcal meningitis

Bacterial meningitis is characterized by an inflammatory reaction to the invading pathogens that can ultimately lead to sensorineural hearing loss, permanent brain injury, or death. The matrix metalloproteinases (MMPs) and tumor necrosis factor alpha-converting enzyme (TACE) are key mediators that promote inflammation, blood-brain barrier disruption, and brain injury in bacterial meningitis. Doxycycline is a clinically used antibiotic with anti-inflammatory effects that lead to reduced cytokine release and the inhibition of MMPs. Here, doxycycline inhibited TACE with a 50% inhibitory dose of 74 microM in vitro and reduced the amount of tumor necrosis factor alpha released into the cerebrospinal fluid by 90% in vivo. In an infant rat model of pneumococcal meningitis, a single dose of doxycycline (30 mg/kg) given as adjuvant therapy in addition to ceftriaxone 18 h after infection significantly reduced the mortality, the blood-brain barrier disruption, and the extent of cortical brain injury. Adjuvant doxycycline (30 mg/kg given subcutaneously once daily for 4 days) also attenuated hearing loss, as assessed by auditory brainstem response audiometry, and neuronal death in the cochlear spiral ganglion at 3 weeks after infection. Thus, doxycycline, probably as a result of its anti-inflammatory properties, had broad beneficial effects in the brain and the cochlea and improved survival in this model of pneumococcal meningitis in infant rats.

Statistical evaluation of time-dependent metabolite concentrations: estimation of post-mortem intervals based on in situ 1H-MRS of the brain

Knowledge of the time interval from death (post-mortem interval, PMI) has an enormous legal, criminological and psychological impact. Aiming to find an objective method for the determination of PMIs in forensic medicine, 1H-MR spectroscopy (1H-MRS) was used in a sheep head model to follow changes in brain metabolite concentrations after death. Following the characterization of newly observed metabolites (Ith et al., Magn. Reson. Med. 2002; 5: 915-920), the full set of acquired spectra was analyzed statistically to provide a quantitative estimation of PMIs with their respective confidence limits. In a first step, analytical mathematical functions are proposed to describe the time courses of 10 metabolites in the decomposing brain up to 3 weeks post-mortem. Subsequently, the inverted functions are used to predict PMIs based on the measured metabolite concentrations. Individual PMIs calculated from five different metabolites are then pooled, being weighted by their inverse variances. The predicted PMIs from all individual examinations in the sheep model are compared with known true times. In addition, four human cases with forensically estimated PMIs are compared with predictions based on single in situ MRS measurements. Interpretation of the individual sheep examinations gave a good correlation up to 250 h post-mortem, demonstrating that the predicted PMIs are consistent with the data used to generate the model. Comparison of the estimated PMIs with the forensically determined PMIs in the four human cases shows an adequate correlation. Current PMI estimations based on forensic methods typically suffer from uncertainties in the order of days to weeks without mathematically defined confidence information. In turn, a single 1H-MRS measurement of brain tissue in situ results in PMIs with defined and favorable confidence intervals in the range of hours, thus offering a quantitative and objective method for the determination of PMIs.

Expression of proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta in the brain during experimental group B streptococcal meningitis

We performed mRNA in situ hybridization for TNF-alpha and IL-1beta from infant rats with group B streptococcal meningitis. Induction of both cytokines was seen in the ependyma and the meninges at 4 h. Both cytokines were expressed in the brain parenchyma at 12 h. Induction of IL-1beta mRNA was seen in vessels within the brain cortex. Neutrophilic infiltrate at all time points examined was minimal and could not account for the observed cytokine expression.

Event-related electric microstates of the brain differ between words with visual and abstract meaning

The present study shows that different neural activity during mental imagery and abstract mentation can be assigned to well-defined steps of the brain's information-processing. During randomized visual presentation of single, imagery-type and abstract-type words, 27 channel event-related potential (ERP) field maps were obtained from 25 subjects (sequence-divided into a first and second group for statistics). The brain field map series showed a sequence of typical map configurations that were quasi-stable for brief time periods (microstates). The microstates were concatenated by rapid map changes. As different map configurations must result from different spatial patterns of neural activity, each microstate represents different active neural networks. Accordingly, microstates are assumed to correspond to discrete steps of information-processing. Comparing microstate topographies (using centroids) between imagery- and abstract-type words, significantly different microstates were found in both subject groups at 286–354 ms where imagery-type words were more right-lateralized than abstract-type words, and at 550–606 ms and 606–666 ms where anterior-posterior differences occurred. We conclude that language-processing consists of several, well-defined steps and that the brain-states incorporating those steps are altered by the stimuli's capacities to generate mental imagery or abstract mentation in a state-dependent manner.