Browsing by Author "Spitsbergen, John"

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A case-control study on the driving factors of childhood brain volume loss: What pediatricians must explore
(PLOS ONE, 2022-12-30) Sungura, Richard; Shirima, Gabriel; Spitsbergen, John; Mpolya, Emmanuel; Vianney, John-Mary
Background The brain volume loss also known as brain atrophy is increasingly observed among children in the course of performing neuroimaging using CT scan and MRI brains. While severe forms of brain volume loss are frequently associated with neurocognitive changes due to effects on thought processing speed, reasoning and memory of children that eventually alter their general personality, most clinicians embark themselves in managing the neurological manifestations of brain atrophy in childhood and less is known regarding the offending factors responsible for developing pre-senile brain atrophy. It was therefore the goal of this study to explore the factors that drive the occurrence of childhood brain volume under the guidance of brain CT scan quantitative evaluation. Methods This study was a case-control study involving 168 subjects with brain atrophy who were compared with 168 age and gender matched control subjects with normal brains on CT scan under the age of 18 years. All the children with brain CT scan were subjected to an intense review of their birth and medical history including laboratory investigation reports. Results Results showed significant and influential risk factors for brain atrophy in varying trends among children including age between 14-17(OR = 1.1), male gender (OR = 1.9), birth outside facility (OR = 0.99), immaturity (OR = 1.04), malnutrition (OR = 0.97), head trauma (OR = 1.02), maternal alcoholism (OR = 1.0), antiepileptic drugs & convulsive disorders (OR = 1.0), radiation injury (OR = 1.06), space occupying lesions and ICP (OR = 1.01) and birth injury/asphyxia (OR = 1.02). Conclusions Pathological reduction of brain volume in childhood exhibits a steady trend with the increase in pediatric age, with space occupying lesions & intracranial pressure being the most profound causes of brain atrophy.
Cholinergic neurons regulate secretion of glial cell line-derived neurotrophic factor by skeletal muscle cells in culture.
(Elsevier, 2011-05-16) Vianney, John-Mary; Spitsbergen, John
Glial cell line-derived neurotrophic factor (GDNF) has been identified as a potent survival factor for both central and peripheral neurons. GDNF has been shown to be a potent survival factor for motor neurons during programmed cell death and continuous treatment with GDNF maintains hyperinnervation of skeletal muscle in adulthood. However, little is known about factors regulating normal production of endogenous GDNF in skeletal muscle. This study aimed to examine the role that motor neurons play in regulating GDNF secretion by skeletal muscle. A co-culture of skeletal muscle cells (C2C12) and cholinergic neurons, glioma×neuroblastoma hybrid cells (NG108-15) were used to create nerve-muscle interactions in vitro. Acetylcholine receptors (AChRs) on nerve-myotube co-cultures were blocked with alpha-bungarotoxin (α-BTX). GDNF protein content in cells and in culture medium was analyzed by enzyme-linked immunosorbant assay (ELISA) and western blotting. GDNF localization was examined by immunocytochemistry. The nerve-muscle co-culture study indicated that the addition of motor neurons to skeletal muscle cells reduced the secretion of GDNF by skeletal muscle. The results also showed that blocking AChRs with α-BTX reversed the action of neural cells on GDNF secretion by skeletal muscle. Although ELISA results showed no GDNF in differentiated NG108-15 cells grown alone, immunocytochemical analysis showed that GDNF was localized in NG108-15 cells co-cultured with C2C12 myotubes. These results suggest that motor neurons may be regulating their own supply of GDNF secreted by skeletal muscle and that activation of AChRs may be involved in this process.
Effects of acetylcholine and electrical stimulation on glial cell line-derived neurotrophic factor production in skeletal muscle cells
(Elsevier, 2014-11-07) Vianney, John-Mary; Miller, Damon; Spitsbergen, John
Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor required for survival of neurons in the central and peripheral nervous system. Specifically, GDNF has been characterized as a survival factor for spinal motor neurons. GDNF is synthesized and secreted by neuronal target tissues, including skeletal muscle in the peripheral nervous system; however, the mechanisms by which GDNF is synthesized and released by skeletal muscle are not fully understood. Previous results suggested that cholinergic neurons regulate secretion of GDNF by skeletal muscle. In the current study, GDNF production by skeletal muscle myotubes following treatment with acetylcholine was examined. Acetylcholine receptors on myotubes were identified with labeled alpha-bungarotoxin and were blocked using unlabeled alpha-bungarotoxin. The question of whether electrical stimulation has a similar effect to that of acetylcholine was also investigated. Cells were stimulated with voltage pulses; at 1 and 5 Hz frequencies for times ranging from 30 min to 48 h. GDNF content in myotubes and GDNF in conditioned culture medium were quantified by enzyme-linked immunosorbant assay. Results suggest that acetylcholine and short-term electrical stimulation reduce GDNF secretion, while treatment with carbachol or long-term electrical stimulation enhances GDNF production by skeletal muscle.
The focused quantitative EEG bio-marker in studying childhood atrophic encephalopathy
(Springer Nature Limited, 2022-08-04) Sungura, Richard; Shirima, Gabriel; Spitsbergen, John; Mpolya, Emmanuel; John‑Mary, Vianney
Although it is a normal involution process in advanced age, brain atrophy—also termed atrophic encephalopathy—can also occur prematurely in childhood as a consequential efect of brain tissues injury through trauma or central nervous system infection, though in both normal and premature occurrences this condition always presents with loss of volume relative to the skull. A common tool for the functional study of brain activities is an electroencephalogram, but analyses of this have reportedly identifed mismatches between qualitative and quantitative forms, particularly in the use of Delta-alpha ratio (DAR) indices, meaning that the values may be case dependent. The current study thus examines the value of Focused Occipital Beta-Alpha Ratio (FOBAR) as a modifed biomarker for evaluating brain functional changes resulting from brain atrophy. This cross-sectional design study involves 260 patients under 18 years of age. Specifcally, 207 patients with brain atrophy are compared with 53 control subjects with CT scan-proven normal brain volume. All the children underwent digital electroencephalography with brain mapping. Results show that alpha posterior dominant rhythm was present in 88 atrophic children and 44 controls. Beta as posterior dominant rhythm was present in an overwhelming 91.5% of atrophic subjects, with 0.009 p-values. The focused occipital Beta-alpha ratio correlated signifcantly with brain volume loss presented in diagonal brain fraction. The FOBAR and DAR values of the QEEG showed no signifcant correlation. This work concludes that QEEG cerebral dysfunctional studies may be etiologically and case dependent from the nature of the brain injury. Also, the focused Beta-alpha ratio of the QEEG is a prospective and potential biomarker of consideration in studying childhood atrophic encephalopathy
The neurochemistry and social flow of singing: bonding and oxytocin.
(Frontiers in Human Neuroscience, 2015-09-23) Keeler, Jason; Roth, Edward; Neuser, Brittany; Spitsbergen, John; Waters, Daniel; Vianney, John-Mary
Music is used in healthcare to promote physical and psychological well-being. As clinical applications of music continue to expand, there is a growing need to understand the biological mechanisms by which music influences health. Here we explore the neurochemistry and social flow of group singing. Four participants from a vocal jazz ensemble were conveniently sampled to sing together in two separate performances: pre-composed and improvised. Concentrations of plasma oxytocin and adrenocorticotropic hormone (ACTH) were measured before and after each singing condition to assess levels of social affiliation, engagement and arousal. A validated assessment of flow state was administered after each singing condition to assess participants' absorption in the task. The feasibility of the research methods were assessed and initial neurochemical data was generated on group singing. Mean scores of the flow state scale indicated that participants experienced flow in both the pre-composed (M = 37.06) and improvised singing conditions (M = 34.25), with no significant difference between conditions. ACTH concentrations decreased in both conditions, significantly so in the pre-composed singing condition, which may have contributed to the social flow experience. Mean plasma oxytocin levels increased only in response to improvised singing, with no significant difference between improvised and pre-composed singing conditions observed. The results indicate that group singing reduces stress and arousal, as measured by ACTH, and induces social flow in participants. The effects of pre-composed and improvised group singing on oxytocin are less clear. Higher levels of plasma oxytocin in the improvised condition may perhaps be attributed to the social effects of improvising musically with others. Further research with a larger sample size is warranted.