Microdialysis-Based Classifications of Abnormal Metabolic States after Traumatic Brain Injury: A Systematic Review of the Literature

Venturini, Sara; Bhatti, Faheem; Timofeev, Ivan; Carpenter, Keri L.H.; Hutchinson, Peter J.; Guilfoyle, Mathew R.; Helmy, Adel

doi:10.1089/neu.2021.0502

Cited by 7 publications

(4 citation statements)

References 76 publications

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“…Measurement of P bt O 2 , CPP and arterial oxygen saturation has been used to guide treatment of cerebral hypoxia in severe TBI, helping to uncover physiologic states that may lead to impaired brain oxygen metabolism [ 115 ]. CMD-based parameters, including LPR and pH, can directly characterize cerebral metabolic states, including ischemia, metabolic stress, and mitochondrial dysfunction [ 107 , 124 ], and has been shown to predict cerebral metabolic crisis and disruptions in cerebral perfusion requiring therapeutic intervention [ 110 , 119 ]. The identification of metabolic derangement, including mitochondrial dysfunction via CMD-based MMM, has also been used to guide targeted metabolic treatment of TBI [ 111 ].…”

Section: Resultsmentioning

confidence: 99%

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Lynch

Narayan

2023

JCM

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

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Section: Resultsmentioning

confidence: 99%

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Lynch

Narayan

2023

JCM

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“…In vivo microdialysis has been applied in human subjects in areas such as brain tumors [ 45 ], traumatic brain injury [ 73 ], and stroke [ 14 ], however, exploratory biomarker research in humans using invasive techniques, such as in vivo microdialysis, is highly discouraged. For this purpose, a more plausible scientific approach is the use of animal models for direct investigation of ECF by in vivo microdialysis to find potential novel biomarkers or target molecules, which should be followed by human CSF and serum analysis for verification and translation.…”

Section: Discussionmentioning

confidence: 99%

“…We initiated an animal model study of brain tissue-related peptidome of the ECF to reveal cellular processes reflected in the dialysate. We note that microdialysis can also be performed in human subjects for monitoring extracellularly available molecules [ 14 , 73 ]. To validate the concept that brain cells release peptides in correlation with changes in cellular processes in physiological and pathological conditions, we selected an epilepsy model for the peptidome analysis.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of hippocampal extracellular space uncovers widely altered peptidome upon epileptic seizure in urethane-anaesthetized rats

Tukacs,

Mittli,

Hunyadi-Gulyás

et al. 2024

Fluids Barriers CNS

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Background The brain extracellular fluid (ECF), composed of secreted neurotransmitters, metabolites, peptides, and proteins, may reflect brain processes. Analysis of brain ECF may provide new potential markers for synaptic activity or brain damage and reveal additional information on pathological alterations. Epileptic seizure induction is an acute and harsh intervention in brain functions, and it can activate extra- and intracellular proteases, which implies an altered brain secretome. Thus, we applied a 4-aminopyridine (4-AP) epilepsy model to study the hippocampal ECF peptidome alterations upon treatment in rats. Methods We performed in vivo microdialysis in the hippocampus for 3–3 h of control and 4-AP treatment phase in parallel with electrophysiology measurement. Then, we analyzed the microdialysate peptidome of control and treated samples from the same subject by liquid chromatography-coupled tandem mass spectrometry. We analyzed electrophysiological and peptidomic alterations upon epileptic seizure induction by two-tailed, paired t-test. Results We detected 2540 peptides in microdialysate samples by mass spectrometry analysis; and 866 peptides—derived from 229 proteins—were found in more than half of the samples. In addition, the abundance of 322 peptides significantly altered upon epileptic seizure induction. Several proteins of significantly altered peptides are neuropeptides (Chgb) or have synapse- or brain-related functions such as the regulation of synaptic vesicle cycle (Atp6v1a, Napa), astrocyte morphology (Vim), and glutamate homeostasis (Slc3a2). Conclusions We have detected several consequences of epileptic seizures at the peptidomic level, as altered peptide abundances of proteins that regulate epilepsy-related cellular processes. Thus, our results indicate that analyzing brain ECF by in vivo microdialysis and omics techniques is useful for monitoring brain processes, and it can be an alternative method in the discovery and analysis of CNS disease markers besides peripheral fluid analysis.

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“…The technique can also be used to determine the concentration of drugs in different brain tissues as well as changes in the concentration of non-binding drugs in the brain’s extracellular fluid over time. This technology has become indispensable in the study of brain-targeting drugs and their active pharmacological effects in the CNS, and it is suitable for in vivo biochemical and deep brain region research ( Venturini et al, 2023 ). However, this method has high instrument requirements and costs, and it is not conducive to large-scale experiments.…”

Section: Common Experimental Methods Used In Intranasal Drug Delivery...mentioning

confidence: 99%

Research progress in brain-targeted nasal drug delivery

Huang,

Chen,

et al. 2024

Front. Aging Neurosci.

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The unique anatomical and physiological connections between the nasal cavity and brain provide a pathway for bypassing the blood–brain barrier to allow for direct brain-targeted drug delivery through nasal administration. There are several advantages of nasal administration compared with other routes; for example, the first-pass effect that leads to the metabolism of orally administered drugs can be bypassed, and the poor compliance associated with injections can be minimized. Nasal administration can also help maximize brain-targeted drug delivery, allowing for high pharmacological activity at lower drug dosages, thereby minimizing the likelihood of adverse effects and providing a highly promising drug delivery pathway for the treatment of central nervous system diseases. The aim of this review article was to briefly describe the physiological structures of the nasal cavity and brain, the pathways through which drugs can enter the brain through the nose, the factors affecting brain-targeted nasal drug delivery, methods to improve brain-targeted nasal drug delivery systems through the application of related biomaterials, common experimental methods used in intranasal drug delivery research, and the current limitations of such approaches, providing a solid foundation for further in-depth research on intranasal brain-targeted drug delivery systems (see Graphical Abstract).

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Microdialysis-Based Classifications of Abnormal Metabolic States after Traumatic Brain Injury: A Systematic Review of the Literature

Cited by 7 publications

References 76 publications

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Comparative analysis of hippocampal extracellular space uncovers widely altered peptidome upon epileptic seizure in urethane-anaesthetized rats

Research progress in brain-targeted nasal drug delivery

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