Ischemia Triggered Glutamate Excitotoxicity Manuscript Review

1 Running Head: HUMAN ASTROCYTES Human Astrocytes Name Institution affiliation Date 2 HUMAN ASTROCYTES Astrocyte and glial ratios The glial ratio increases during evolution depending on the different bodies of species. The human brain contains a glial ratio of one-to-one and the cerebral cortex of 1.4. During evolution, large mammals like savannah elephants increase the glial ratio by 80%. The change in the glianeurons ratio can result from the correlation between the number of glial and the density of neuronal density. Astrocytes tend to differ due to the glial population of different species (Vasile, 2017). Astrocyte Subpopulations within Human Brain Interlaminar Astroglia –The anatomical location of this type of astrocyte is in layers I and II of the cortex. This type of astroglia has a multilamellar structure and mitochondria. The role of interlaminar astroglia in Alzheimer’s disease and Down syndrome provides neuronal support to the brain. Protoplasmic Astroglia -The anatomical location of protoplasmic astroglia is in layers III and IV of the cortex. The protoplasmic astroglia is characterized as bulbous because of the diolistic labeling process and GFAP processes. Protoplasmic astroglia is used to modulate and integrate inter-neuronal communication among several synapses. Also, it provides exceptional computational power. Varicose Projections Astroglia -The anatomical location of varicose projection astrocyte is in layers V and VI of the cortex. This type of astrocytes has long fibers structures with varicosities. Varicose projection astroglia plays a role in the cognitive functions of a human. The varicosities in varicose projection astrocytes ensure compartmentalization and communication among subcellular sections and cortical layers. 3 HUMAN ASTROCYTES Fibrous Astroglia – The anatomical location of fibrous astroglia is in the white matter in the cerebral cortex. They are large, have straight processes, are less branched, and have few fine processes. Fibrous astroglia plays a role in supporting metabolic processes in the vasculature. Fibrous astroglia tend to be distant from each other so as to provide full support to the axon tract. Functions for Human Astrocytes Neuronal Survival and Synaptogenesis Human astrocytes provide neuronal survival, where the astrocytes contribute to synapses and engulfment of synaptosomes. Ischemia Triggered Glutamate Excitotoxicity Manuscript Review

The secretion of the growth factor in human astrocytes promotes synapses through the process of D-serine mediation (Vasile, 2017). Also, human astrocytes promote neuronal survival. Electrophysiology Human astrocytes have a larger capacitance which helps in increasing the size of soma and proximal processes. Unlike rodent astrocytes, the human astrocyte is highly increased for membrane resistance. The membrane resistance has a constant length to allow further transmission of current within the brain. Intercellular Coupling Intercellular coupling allows the exchange of neuromodulators, metabolites, and ions. Also, the human astrocyte mediates signal in-network upscale. The availability of connexins in human astrocytes is used for the modulation of protein expression. The availability of gap junction (GJ) is the major astroglia function as a sub-unit of astrocytes. Neurotransmitter Recycling and Uptake HUMAN ASTROCYTES 4 The human astrocyte contains glutamine transporters that help the human brain colocalize with astrocytes to avoid excitotoxicity. The glutamate transporters are expressed and functional for transient inward currents. Neurotransmitters are used in support of energy production. Calcium Signaling and Gliotransmission. The presence of signaling-related proteins and calcium transients in human astrocytes helps in gliotransmission. The low nature of human astrocytes helps detect synaptic activities within the brain. Increased speed of propagation is a result of the enlargement of astrocytes. The availability of glutamate in mature astrocytes lead to an increase in intracellular calcium through the glutamate receptor 5. 5 HUMAN ASTROCYTES Reference Vasile, F., Dossi, E., & Rouach, N. (2017). Human astrocytes: structure and functions in the healthy brain. Brain Structure and Function, 222(5). 1 Running Head: MANUSCRIPT REVIEW Manuscript Review Name Institution affiliation Date 2 MANUSCRIPT REVIEW Models Used in Research The research used multiple imputation models for variables between 6%-20%. The imputation models used include linear, logistic, ordered logistic, and predictive mean matching. For instance, linear imputation executes customarily distributed variables. Logistic executes binary variable, predictive mean matching uses continuous skewed variables and ordered logistic imputation model uses ordinal variables. Ischemia Triggered Glutamate Excitotoxicity Manuscript Review

The technique used was logistic regression, where combined results from Rubin rules determined variability in estimates. The parameters of disease progression were bacterial infection and viral infections. The research compared patients with bacterial infections to those with a viral infection, leaving out the patients with viral and bacterial infections. The type of experimental model used was multivariate logistic regression models. Logistic regression models depend on the dependent variables. For example, in this case, the multivariate logistic regression depends on bacterial infection, viral infection, or death as a dependent variable. Therefore, in this model, all factors in the models are included when doing a univariate analysis. Overview and Interpretation of Results Diagnostic laboratory tests were carried out to confirm etiology in patients with bacterial or viral infections. The diagnostic tests include seroconversion, detection of pathogens in blood, and cerebrospinal in the central nervous system. After a series of test results to detect pathogens, it was confirmed that etiology was present. Therefore, etiology confirmed that patients with mono infections were more, whereas patients with co-infections were fewer. From the results, it is empirical that a higher percentage of etiology cases were patients with enterovirus, while a lower 3 MANUSCRIPT REVIEW percentage of nonenterovirus patients were rarely affected by etiology. The nonentorovirus cases were primarily children. Caveats to the Findings The first caveat of the findings is that the study used the Japanese encephalitis virus (JEV), yet it has a low predictive value. The JEV makes the findings to be overestimated. The second caveat is that the study used patients who had received an antibiotic before lumbar puncture. The presence of an antibiotic in a patient’s body reduces the bacterial load used in molecular detection. The presence of antibiotics in the body leads to the underestimation of bacterial substances in the system. There was a high mortality rate in the study. The high mortality rate can be associated with poor patient management in the research. However, the epidemiology studies vary from one geographical area to another. Therefore, studies carried within a specific geographical area cannot apply or be used in a different geographical area. Also, the study used partially stored samples. There was a lack of postmortem examination and missing values. There were no brain scans and magnetic resonance imaging in some of the cases used in the study. Findings for Potential Therapeutic Targeting The study has focused on etiology patients with viral and bacterial infections. The study should not have classified patients into different groups to avoid non-distinguishable manifestations. Bacteria in the body as a result of Central nervous system infection leads to diabetes. Therefore, diabetes is a risk stimulation in a bacterial central nervous system infection. Also, as bacterial infection in the body increases the level of blood glucose resulting in diabetes. From the research, there are two methods of improving patient survival. The first method is the use of antibiotic guidelines. The second method is to strengthen the high-dependency units. …