{"doi":"10.1016/j.ibneur.2023.08.2190","title":"THE CONSEQUENCES OF ENHANCED GLUTAMATERGIC NEUROTRANSMISSION IN DNA DAMAGE IN SUBJECTS WITH EPILEPSY OR WITH TRAUMATIC BRAIN INJURY","abstract":"The present presentation was designed to show evidence of the enhanced glutamatergic neurotransmission in two neurological disorders (epilepsy and traumatic brain injury (TBI)), as well as two different therapeutic strategies that maintain glutamate homeostasis and preserve normal brain function. Hydrogen sulfide (H2S) is a gasotransmitter that promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. On the other hand, epilepsy and TBI are associated with mitochondrial stress and reduced expression of H2S. Studies support that H2S represents a potential therapeutic strategy to avoid epileptogensis as well as alterations induced by severe TBI. H2S prevents epilepsy and the TBI-induced consequences by reducing oxidative stress because of its direct effect on ROS scavenging, and its ability to upregulate the endogenous antioxidant defense system. Cannabidiol (CBD), the major non-psychotomimetic compound of the Cannabis sativa plant, is a multitarget molecule with neuroprotective effects in different brain disorders, including epilepsy and TBI. Preclinical studies support that CBD administration decreases short- and long-term glutamate over-release after severe TBI, an effect associated with improvement of sensorimotor activity, as well as lower mortality. Concerning epilepsy, acute exposure to CBD reduces glutamate release from cortical synaptic terminals obtained from patients with drug-resistant temporal lobe epilepsy. It is possible to suggest that CBD avoids the glutamate-induced excitotoxicity and neuronal damage of patients with epilepsy. The lower glutamate release induced by CBD is explained by a decrease in calcio release with a consequent reduction in proinflammatory cytokine expression, oxidative stress, and neurodegeneration. Excessive extracellular levels of glutamate found in epilepsy and TBI result in excitotoxicity, leading to high influx of calcium that eventually leads to DNA damage, apoptosis and cell death. All these changes produce mitochondrial dysfunction and damage to the mitochondrial DNA. H2S and CBD represent novel therapeutic strategies to avoid DNA damage. None","journal":"IBRO Neuroscience Reports","year":2023,"id":413656,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":480730,"name":"Luísa Rocha","orcid":"0000-0003-4495-9427","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:21:57.641539Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}