Investigating Molecular Mechanisms and Therapeutic Strategies in Tuberculous Meningitis

Tuberculous Meningitis (TBM) is the most severe form of extrapulmonary tuberculosis, posing a critical global health challenge. This devastating central nervous system infection frequently leads to severe disability, long-term neurological sequelae, and high mortality rates. The brain, an exceptionally energy-demanding organ, relies on precise regulation of neuroenergetics. In TBM, severe inflammation, hypoxic-ischemic injury, and direct mycobacterial effects profoundly disrupt these vital processes, significantly impacting diverse clinical characteristics, disease progression, and patient outcomes.A deeper understanding of the intricate molecular, cellular, and systems-level mechanisms underpinning TBM is crucial. This includes exploring host energy metabolism, its metabolic upbring (i.e., the genetic, environmental, and developmental factors shaping an individual's metabolic profile), its dysregulation, and the extensive molecular reprogramming that occurs during infection. This knowledge is essential for developing effective diagnostics, novel pharmacological interventions, adjunctive therapies, and ultimately, improving prognosis through robust clinical trials.This Research Topic aims to comprehensively investigate the fundamental host mechanisms and pathophysiology specific to TBM, focusing on neuro-energetic dysfunction and broad molecular alterations induced by Mycobacterium tuberculosis in the CNS. We seek to explore the complex metabolic interplay during TBM, translating basic scientific insights into improved understanding of TBM's unique clinical characteristics, the development of targeted intervention strategies, and the design of impactful clinical trials. We welcome submissions on the following research areas:• Mitochondrial Biology and Dysfunction in TBM: Research on host mitochondrial dynamics, bioenergetics, oxidative stress, and quality control, examining their roles in TBM pathogenesis, inflammatory response, brain injury, and their potential as therapeutic targets.• Neuronal-Glial Metabolic Coupling in TBM Pathogenesis: Studies on disrupted neuronal-glial metabolic coupling in TBM, including astrocyte-neuron lactate shuttle, glucose transport, and fatty acid metabolism, and their roles in inflammation, brain injury, and post-treatment recovery.• Molecular (transcriptomic, proteomic, and metabolomic) Reprogramming and Host Physiological Upheaval in TBM: Investigation of global molecular shifts and altered glucose, ketone, and amino acid metabolism in TBM. This includes assessing their metabolic upbring (e.g., host genetics, nutrition) and impact on disease onset, severity, progression, neurological complications, and specific clinical characteristics of TBM.• Pharmacological and Non-Pharmacological Interventions for TBM, and Clinical Trials: Development and testing of novel pharmacological interventions (e.g., host-directed therapies, neuroprotectants) and non-pharmacological strategies (e.g., nutritional support) to modulate host brain metabolism in TBM. Submissions evaluating efficacy in preclinical models and translation into clinical trials to improve TBM patient prognosis and neurological outcomes are highly encouraged.• Advanced Metabolic Imaging and Biomarkers for TBM: Application of advanced metabolic imaging (PET, MRS, fMRI) and liquid biopsy metabolomics to identify TBM-specific neuroenergetic and molecular biomarkers. This includes biomarkers for early diagnosis, predicting disease severity and prognosis, and monitoring treatment response to anti-tubercular and adjunctive therapies during acute and long-term recovery phases of TBM. Topic editors: Shayne Mason, James Alexander Seddon Source: https://www.frontiersin.org/research-topics/75841/investigating-molecular-mechanisms-and-therapeutic-strategies-in-tuberculous-meningitis