Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI). Experimental mTBI was induced using a concussive head trauma device. One hour before injury, animals were subjected to MDMA. Administration of MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels that were observed in mTBI mice. This normalization was also able to lower the elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived neurotrophic factor (BDNF) levels did not change following injury alone, but in mice subjected to MDMA and mTBI, significant elevations were observed. In the behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was administered prior to injury. Altered catecholamine synthesis and high D2 receptor levels contribute to cognitive dysfunction, and strategies to normalize TH signaling and D2 levels may provide relief for the deficits observed after injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing regular dopamine system activity. While the beneficial effect we observe was due to a dangerous recreational drug, understanding the alterations in dopamine and the mechanism of dysfunction at a cellular level can lead to legal therapies and potential candidates for clinical use.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s12031-014-0399-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Peritraumatic Context and Long-Term Outcomes of Concussion.
JAMA Netw Open
January 2025
Translational Research Center for TBI and Stress Disorders, Veterans Affairs Boston Healthcare System, Boston, Massachusetts.
Importance: There has been a great deal of interest in mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) and their association with one another, yet their interaction and subsequent associations with long-term outcomes remain poorly understood.
Objective: To compare the long-term outcomes of mTBI that occurred in the context of psychological trauma (peritraumatic context) with mTBI that did not (nonperitraumatic context).
Design, Setting, And Participants: This cohort study of post-9/11 US veterans used data from the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) study at the Veterans Affairs Boston Healthcare System, which began in 2009; the current study utilized data from baseline TRACTS visits conducted between 2009 and 2024.
Traumatic brain injury causes early aggregation of beta-amyloid peptides and NOTCH3 reduction in vascular smooth muscle cells of leptomeningeal arteries.
Acta Neuropathol
January 2025
Department of Clinical Sciences, Lund Brain Injury Laboratory for Neurosurgical Research, Lund University, 222 20, Lund, Sweden.
Traumatic brain injury (TBI) often leads to impaired regulation of cerebral blood flow, which may be caused by pathological changes of the vascular smooth muscle cells (VSMCs) in the arterial wall. Moreover, these cerebrovascular changes may contribute to the development of various neurodegenerative disorders such as Alzheimer's-like pathologies that include amyloid beta aggregation. Despite its importance, the pathophysiological mechanisms responsible for VSMC dysfunction after TBI have rarely been evaluated.
View Article and Find Full Text PDFPost-craniectomy hydrocephalus in adult traumatic brain injury patients: a systematic review and meta-analysis of risk factors and outcome.
Neurosurg Rev
January 2025
Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Traumatic Brain Injury (TBI) is a major cause of death, disability, and healthcare expenses worldwide. Decompressive craniectomy (DC) is a critical surgery used when there is uncontrollable swelling in the brain following a TBI. Research has shown that 27.
View Article and Find Full Text PDFAntiseizure medication use in acute symptomatic seizures: A narrative review.
Epilepsia
January 2025
Epilepsy Center, Cleveland Clinic, Cleveland, Ohio, USA.
Acute symptomatic seizures, occurring shortly after a central nervous system insult, constitute nearly half of all seizure cases. However, there is a conspicuous absence of clear, comprehensive, and cohesive guidelines for the management of these seizures with antiseizure medications, especially their duration of use. This lack of consensus on the optimal duration of therapy leads to prolonged treatments that may carry adverse consequences.
View Article and Find Full Text PDFThe weight of multiple hits: how TBI and infectious encephalitis co-modulate adverse outcomes.
Brain Inj
January 2025
Department of Biomedical Science and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, USA.
Background: Chronic neurologic deficits from traumatic brain injury (TBI) and subsequent infectious encephalitis are poorly characterized.
Methods: Using TriNetX database we queried patients 18 years or older with a confirmed diagnosis of encephalitis between 2016 and 2024. Patient cohorts included those with a diagnosis of TBI at least one month before encephalitis ( = 1,038), those with a diagnosis of a TBI anytime before encephalitis ( = 1,886), and those with encephalitis but no TBI, ( = 45,210; = 45,215).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!