Current preclinical studies on neuroinflammation and changes in blood-brain barrier integrity by MDMA and
Esther O'Shea1, Andrés Urrutia1, A Richard Green2
1Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid 28040, Spain.
Abstract:
The blood-brain barrier (BBB) is essential in the maintenance of brain homeostasis both by preserving normal brain functioning and also by protecting the brain from exposure to a range of potentially harmful substances. This review presents some of the evidence of BBB disruption following exposure to the substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methamphetamine (METH), two drugs of abuse which are widely consumed recreationally by younger sectors of the population. Both MDMA and METH have been shown to produce disruption of the BBB as reflected by IgG extravasation and Evans Blue leakage. In particular, METH decreases the expression of basal lamina proteins associated with an increase in matrix metalloproteinase activity. These changes in BBB integrity appear to be related to MDMA-induced activation of the mitogen-activated protein kinase (MAPK) JNK1/2. The consequences of the disruption in the BBB by these two drugs remain to be established, but there is evidence in the literature that, at least in the case of METH, increased matrix metalloproteinase (MMP) activity may be related to increased behavioural sensitization and reward perhaps because of the modification of the passage of the drug into the CNS. In addition, the high incidence of AIDS-related neurologic disease in METH users may also be related to increased entry into the brain of virally derived neurotoxic products. This article is part of the Special Issue entitled 'CNS Stimulants'.
Insights
Recreational amphetamines like MDMA and methamphetamine disrupt the blood-brain barrier (BBB), potentially impacting brain function and increasing vulnerability to neurological issues. Further research is needed to understand the full consequences of this BBB disruption.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- The blood-brain barrier (BBB) is crucial for maintaining brain homeostasis and protecting the central nervous system.
- Substituted amphetamines, including MDMA and methamphetamine (METH), are widely used recreational drugs with potential neurotoxic effects.
- Evidence suggests these drugs can compromise BBB integrity.
Purpose of the Study:
- To review the evidence of blood-brain barrier (BBB) disruption caused by 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH).
- To explore the mechanisms and potential consequences of BBB disruption induced by these amphetamines.
Main Methods:
- Review of existing literature on BBB integrity following exposure to MDMA and METH.
- Analysis of studies measuring IgG extravasation and Evans Blue leakage as indicators of BBB permeability.
- Examination of molecular changes, including basal lamina proteins, matrix metalloproteinase (MMP) activity, and MAPK signaling.
Main Results:
- Both MDMA and METH cause BBB disruption, evidenced by increased IgG extravasation and Evans Blue leakage.
- Methamphetamine (METH) reduces basal lamina proteins and increases MMP activity.
- MDMA-induced BBB changes are linked to the activation of the MAPK JNK1/2 pathway.
Conclusions:
- MDMA and METH disrupt the blood-brain barrier (BBB), affecting brain homeostasis.
- METH-induced BBB disruption may contribute to behavioral sensitization and increased drug reward.
- Compromised BBB in METH users might facilitate the entry of neurotoxic products, potentially exacerbating neurological diseases like AIDS-related conditions.
