Persistent cognitive deficits, induced by intrathecal methotrexate, are associated with elevated CSF concentrations of excitotoxic glutamate analogs and can be reversed by an NMDA antagonist

@article{Vijayanathan2011PersistentCD,
  title={Persistent cognitive deficits, induced by intrathecal methotrexate, are associated with elevated CSF concentrations of excitotoxic glutamate analogs and can be reversed by an NMDA antagonist},
  author={V. Jeyanny Vijayanathan and Maria E. Gulinello and Nafeeza F. Ali and Peter D. Cole},
  journal={Behavioural Brain Research},
  year={2011},
  volume={225},
  pages={491-497}
}
For patients with acute lymphoblastic leukemia or non-Hodgkin lymphoma, intrathecal (IT) methotrexate (MTX) significantly reduces the risk of relapse within the central nervous system, but is associated with neurotoxic sequelae. We established a rat model of MTX-induced cognitive deficits to further investigate the underlying pathophysiology and to develop protective therapeutic interventions. IT MTX 0.5 mg/kg was administered to 10-week old male Long Evans rats. Cerebrospinal fluid (CSF) was… Expand
Methotrexate Affects Cerebrospinal Fluid Folate and Tau Levels and Induces Late Cognitive Deficits in Mice
TLDR
Adult neurocognitive sequelae in a mouse model is demonstrated that can be attributed to the biochemical and cellular impact of early-life methotrexate exposure. Expand
Memantine Protects Rats Treated with Intrathecal Methotrexate from Developing Spatial Memory Deficits
TLDR
Memantine, an NMDA receptor antagonist, reduces the incidence of cognitive deficits in rats treated with intrathecal methotrexate, and may therefore benefit patients with cancer receiving similar treatment. Expand
Methotrexate causes persistent deficits in memory and executive function in a juvenile animal model
TLDR
It is demonstrated that a clinically relevant regimen of systemic and intrathecal methotrexate induces persistent deficits in spatial pattern memory, visual recognition memory and executive function, lasting at least 8 weeks after the last injection. Expand
Hesperidin Alleviates Methotrexate-Induced Memory Deficits via Hippocampal Neurogenesis in Adult Rats
TLDR
Results revealed that Hsd could protect against MTX side effects in the animals in this study, and co-administration with MTX and Hsd alleviated memory loss and neurogenesis decline. Expand
The long-term impact of oxaliplatin chemotherapy on rodent cognition and peripheral neuropathy
TLDR
Systemic OX treatment induced lasting effects on cognitive function at 11 months after treatment, and peripheral neuropathy at 1 month after treatment and these were dose dependent; higher doses of OX resulted in worse cognitive outcomes and more severe peripheral neuropathies. Expand
Review of dextromethorphan administration in 18 patients with subacute methotrexate central nervous system toxicity.
TLDR
Earlier administration of dextromethorphan resulted in faster improvement of impairments and led to prevention of recurrence of seizure activity induced by methotrexate central nervous system toxicity. Expand
Cognitive impairment induced by permanent bilateral common carotid occlusion exacerbates depression-related behavioral, biochemical, immunological and neuronal markers
TLDR
It is shown that cognitive impairment may predispose to depression by intensifying the effect of stress on depression-related behavioral, biochemical, immunological and neuronal markers. Expand
Chemotherapy-Induced Cognitive Impairments : A Systematic and Updated
Chemotherapy-induced cognitive impairment or ‘chemobrain’ is an established clinical syndrome, consisting of cognitive changes in various domains i.e. working memory, executive function and episodicExpand
A Stroke Mimic: Methotrexate-induced Neurotoxicity in the Emergency Department.
TLDR
An 18-year-old woman with a history of ALL presented to the emergency department with acute onset of right-sided facial paralysis, right upper extremity flaccid paralysis, and right lower extremity weakness after receiving MTX therapy 3 days earlier. Expand
Liposomal Cytarabine Induces Less Neurocognitive Dysfunction Than Intrathecal Methotrexate in an Animal Model
TLDR
The data suggest that liposomal cytarabine induces fewer neurocognitive deficits and less acute hematologic toxicity compared with IT MTX, and may have therapeutic advantages over ITMTX, if it is equally effective in preventing relapse. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 39 REFERENCES
Intrathecal methotrexate induces focal cognitive deficits and increases cerebrospinal fluid homocysteine
TLDR
An animal model is established that mimics the clinical effects of prophylactic intrathecal MTX on cognitive function and can further study the pathophysiology of MTX-induced cognitive dysfunction and test protective interventions. Expand
Systemic methotrexate induces spatial memory deficits and depletes cerebrospinal fluid folate in rats
TLDR
Similar to children treated for ALL, rats given systemic MTX develop focal cognitive deficits along with expected alterations in folate physiology. Expand
DEXTROMETHORPHAN IS EFFECTIVE IN THE TREATMENT OF SUBACUTE METHOTREXATE NEUROTOXICITY
TLDR
Using high-performance liquid chromatography with coulometric electrochemical detection, the authors measured CSF Hcy in sequential patients with severe subacute MTX-Ntox, providing support for a placebo-controlled clinical trial to examine the ability of DM to prevent or alleviateMTX-ntox. Expand
Biochemical and Clinical Aspects of Methotrexate Neurotoxicity
TLDR
A better understanding of the pathogenesis of MTX neurotoxicity would offer the possibility of developing new therapeutic strategies for its treatment or prevention. Expand
Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat
TLDR
The studies indicated that, in the rat, MTX has a dose-dependent negative effect on hippocampal cell proliferation, and on cognitive behavior, suggesting that adverse effects of certain cytotoxic agents on hippocampAL cell proliferation may have a potential contributory role in cognitive impairment observed in humans after chemotherapy. Expand
Marked elevation in homocysteine and homocysteine sulfinic acid in the cerebrospinal fluid of lymphoma patients receiving intensive treatment with methotrexate.
TLDR
MTX administered either intravenously or intraventricularly, induced marked biochemical alterations in the CSF and whether these changes can be used to predict MTX-induced neurotoxicity at an early stage in treatment needs to be elucidated in larger clinical trials. Expand
Long-term homocysteine exposure induces alterations in spatial learning, hippocampal signalling and synaptic plasticity
TLDR
It is concluded that healthy adult rats are able to cope with continuous exposure to HCY, and while HCY affects growth and neuronal excitability, this does not precipitate into an immediate impairment of cognitive function. Expand
Methotrexate decreases hippocampal cell proliferation and induces memory deficits in rats
TLDR
The studies suggest that the negative effect of MTX on hippocampal cell proliferation and white matter density may be part of the mechanisms underlying the cognitive impairment observed as side effect after cytotoxic treatment in humans. Expand
Demyelination and single-carbon transfer pathway metabolites during the treatment of acute lymphoblastic leukemia: CSF studies.
TLDR
Treatment of ALL causes marked abnormalities in the single-carbon transfer pathway and subclinical demyelination and whether these abnormalities contribute to the late cognitive deficits requires further study. Expand
Behavioral and Metabolic Changes in Immature Rats during Seizures Induced by Homocysteic Acid: The Protective Effect of NMDA and Non-NMDA Receptor Antagonists
TLDR
The pronounced anticonvulsant effect could be achieved by the combined treatment with low subthreshold doses of NMDA (AP7) and non-NMDA (NBQX) receptor antagonists, which may be of potential significance for a new approach to the treatment of epilepsy. Expand
...
1
2
3
4
...