Exposure to CSF from sporadic amyotrophic lateral sclerosis patients induces morphological transformation of astroglia and enhances GFAP and S100β expression

We have earlier shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients' produces selective degeneration of motor neurons, both in vitro as well as in vivo. The present study further evaluates the effect of ALS-CSF on the astrocytes in embryonic rat spinal cord cultures. We quantified the number of flat and process-bearing astrocytes in spinal cord cultures exposed to ALS-CSF and compared them against controls. In addition, GFAP and S100ß expression were quantified by Western blot and measurement of immunofluorescence intensity respectively. We found higher number of process-bearing astrocytes in the cultures exposed to ALS-CSF. Both these proteins increased significantly in cultures exposed to ALS-CSF. Our results provide evidence that astroglia respond to toxic factor(s) present in ALS-CSF by undergoing morphological transformation from flat to process bearing which is further confirmed by elevated expression of GFAP and S100ß. The above changes could possibly alter the microenvironment hastening the motor neuron degeneration

Modulation of cardiac autonomic functions in patients with major depression treated with repetitive transcranial magnetic stimulation

Background: Sub clinical cardiac autonomic imbalance is associated with depression. Clinical improvement produced by antidepressant therapy might alter this autonomic balance. Objectives: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) therapy on autonomic functions measured by heart rate variability (HRV) in depression patients and compare it with selective serotonin re-up-take inhibitors (SSRI) therapy. Methods: Consecutive drug-naive patients of major depression based on DSM-IV-TR were recruited in this study (n=67). Basal Hamilton depression-rating scale (HDRS) and measures of cardiac autonomic function were recorded and compared with those after two weeks of therapy with rTMS (n=27) and one month after SSRI therapy (n=25). Results: Both therapies produced comparable and significant reduction in HDRS scores. HRV measures indicated that rTMS produced significantly greater reduction in the sympathetic: parasympathetic ratio suggesting improvement in sympathovagal balance. Conventional cardiac autonomic function tests did not differentiate the two therapy effects. Conclusions: rTMS not only produced antidepressant effects but also "corrected" the autonomic imbalance. SSRI was systemically administered and hence by direct cardiac effect, may have masked cardiac effects that would have occurred by the improvement in depression. Alternatively, the neurophysiological "correction" with drug therapy may have longer latency, just as with the therapeutic effects

Cardiac autonomic dysfunctions in chronic refractory epilepsy

Background: Sudden unexplained death is an important cause of mortality in patients with epilepsy and cause for this is not fully understood. One of the explanations is autonomic dysfunction (AD). Studies of AD in chronic refractory epilepsy are very few in the literature. Aim: To evaluate cardiovascular autonomic functions in chronic refractory epilepsy patients. Methods and materials: Seventy-three patients (31.5±9.8 years, M:F::45:28) with chronic intractable epilepsy attending the "refractory epilepsy clinic" at a tertiary referral center (National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India) were enrolled. Age and gender matched healthy subjects were recruited as controls. Heart rate (HR) and blood pressure (BP) at rest and HR response after deep breathing, Valsalva maneuver, postural change and BP response to postural change and isometric work were recorded. AD was graded as early if one of HR or BP, definite if two or more HR and severe if two or more HR with BP based tests were detected to be abnormal. Results: The mean age at onset and duration of epilepsy was 12.4±8.5 years and 19.02±9.07 years, respectively. Twenty-three (31.5%) patients of refractory epilepsy had early involvement while 25 patients (primary generalized: 8, partial: 17) had Definite AD, and 16 (primary generalized: 4, partial: 12) had severe autonomic dysfunction. ANCOVA results showed expiration-inspiration, standing maximum:minimum ratio, standing 2min systolic and isometric diastolic BP of the dysfunction group significantly differ compared to the control group. Patients with longer duration of epilepsy (23.2 years) had more severe dysfunction (p<0.05) than patients with relatively shorter duration (17.5 years) of epilepsy. Antiepileptic drugs (AED) used did not show any significant role on autonomic functions in this study. Conclusion This is the first study from India to evaluate autonomic functions in refractory epilepsy patients. Autonomic dysfunction was noted in 56.3% of patients. Anticonvulsants used were not associated with AD. Longitudinal controlled studies with 'newly diagnosed' epilepsy patients will enhance further understanding about the role of autonomic system in epilepsy

Vascular endothelial growth factor attenuates neurodegenerative changes in the NSC-34 motor neuron cell line induced by cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients

Background: Motor neuron disease or amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord as well as motor cortex. Recently, vascular endothelial growth factor (VEGF) has been identified as a neurotrophic factor in animal models of familial ALS and other neurological diseases. Objective: The present study was designed to investigate the neuroprotective role of VEGF in the more prevalent sporadic form of ALS. Methods: We studied the effect of VEGF on the NSC-34 cell line exposed to cerebrospinal fluid (CSF) from sporadic ALS patients (ALS-CSF) in terms of lactate dehydrogenase (LDH) assay as well as choline acetyltransferase (ChAT) and phosphorylated neurofilament expression by immunocytochemistry and confocal microscopy. NSC-34 cells were exposed to CSF from patients with definite ALS and compared to controls. LDH activity was assessed in the growth media, prior to and 24 h after the addition of VEGF to the cells. At similar time points, the cells were fixed and processed for immunocytochemistry to evaluate ChAT and phosphorylated neurofilament expression. Results: Exposure to ALS-CSF caused morphological changes of NSC-34 cells like reduced differentiation and aggregation of phosphorylated neurofilaments. Enhanced LDH activity and reduced ChAT immunoreactivity were also observed. Addition of VEGF to NSC-34 cells exposed to ALS-CSF was protective in terms of reduced LDH activity and restoration of ChAT expression. Conclusion: The present study confirms that VEGF exerts a neuroprotective effect on the NSC-34 cell line by attenuating the degenerative changes induced by ALS-CSF. It thus has therapeutic potential in sporadic ALS

Influence of age and gender on blood pressure variability and baroreflex sensitivity in a healthy population in the Indian sub-continent

The current exploratory study was aimed at estimating measures of blood pressure variability (BPV) and baroreflex sensitivity (BRS) in a healthy population in the Indian sub-continent. One hundred and forty-two healthy subjects were recruited for the study. Blood pressure (BP) was recorded continuously for 15 min using the Finometer (Finapres Medical Systems, The Netherlands). For offline analysis, Nevrokard cardiovascular parameter analysis (CVPA) software (version 2.1.0) was used for BPV analysis. BRS was determined by spectral and sequence methods. One-way ANOVA and Bonferroni's test were used to compare parameters. Pearson's correlation coefficient was employed to look for possible associations between age and other continuous variables. Out of 196 screened volunteers, 54 were excluded and 142 subjects were grouped based on ages as 10-19 years (group 1), 20-29 years (group 2), 30-39 years (group 3), 40-49 years (group 4), and 50-59 years (group 5). Within groups, body mass index (BMI, p=0.000) and BP (systolic and diastolic) were significantly different. Post hoc analysis showed mean blood pressure (MBP) and diastolic blood pressure (DBP) differing significantly between groups 1 and 4 (p<0.05 for both) along with other cardiovascular parameters. Age correlated positively with BMI and all parameters of BP. Significant gender differences were observed for stroke volume, cardiac output, up BRS, total BRS, peripheral resistance (PR), and aortic impedance. Our study has provided reference values for BPV and BRS in an Indian population. It also indicates age-related neurocardiac imbalance and possible utility of these tests for screening at the start of neurocardiac damage in a healthy population

Autonomic dysfunction: A comparative study of patients with Alzheimer’s and frontotemporal dementia – A pilot study

Introduction: In frontotemporal dementia (FTD) and Alzheimer’s disease (AD), central autonomic structures get affected early. An insight into autonomic functions in these patients is likely to be of diagnostic importance and thus help in prognosticating and also probably explain unexplained sudden death in some of these patients. Objectives: The objective of this study is to identify autonomic dysfunction prevailing in patients. Then, if there is dysfunction, is the pattern same or different in these two conditions. And if different it will serve as an additional biomarker for specific diagnosis. Patients and Methods: There were 25 patients and 25 controls and six patients and three controls in AD and FTD groups, respectively. The participants who were recruited were assessed for heart rate variability and conventional cardiac autonomic function testing. The parameters were analyzed using LabChart version 7 software and compared with control population using appropriate statistical methods using SPSS version 22 software. Results: The mean overall total power was low in the FTD group (P < 0.001), and there was significant reduction in the standard deviation of normal-to-normal intervals and root mean square of successive differences (P < 0.001) with elevated sympathovagal balance in the FTD group (P = 0.04). Patients with AD also showed sympathetic dominance, but there was in addition parasympathetic suppression unlike in the FTD group. Conclusion: This study reveals autonomic dysfunction in patients with FTD and AD. Both conditions show sympathetic dominance, probably consecutive to the involvement of central autonomic regulatory structures as a shared domain. It remains to be confirmed if these findings are the cause or effect of neurodegeneration and might open up newer territories of research based on the causal role of neurotransmitters in these regions and thus lead to novel therapeutic options such as yoga. The presence of parasympathetic suppression in AD in addition helps differentiate these two conditions

L'Avenir de Luchon : journal scientifique, littéraire, annonces et réclames : guide général des baigneurs et des touristes aux eaux thermales, bains de mer de la France et de l'étranger

30 août 19311931/08/30 (N514)-1931/08/30.Appartient à l’ensemble documentaire : MidiPyren