Serum myoglobin, but not lipopolysaccharides, is predictive of AMPH-induced striatal neurotoxicity

Levi, Mark S.; Patton, Ralph E.; Hanig, Joseph P.; Tranter, Karen M.; George, Nysia I.; James, Laura P.; Davis, Kelly J.; Bowyer, John F.

doi:10.1016/j.neuro.2013.04.003

Cited by 6 publications

(15 citation statements)

References 49 publications

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“…Also, the correlation between the magnitude of hyperthermia, serum myoglobin levels (resulting from muscle damage) and neurotoxicity produced by AMPH is very strong 103 as is the correlation between myoglobin and kidney damage 104,105 . However, this is not proof that myoglobin levels are necessarily a causative effect in AMPH neurotoxicity.…”

Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

“…Also, there is some correlation between neurotoxic AMPH exposures with respect to blood nitrogen (BUN) but EIH can also produce similar significant increases in BUN indicating it is necessarily dependent on exposure to neurotoxic doses of AMPH 103 . The muscle damage produced by neurotoxic doses of AMPH, when hyperthermia occurs, also results in increased circulating concentrations of other enzymes such as creatine kinase 103 .…”

Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

“…The muscle damage produced by neurotoxic doses of AMPH, when hyperthermia occurs, also results in increased circulating concentrations of other enzymes such as creatine kinase 103 . Both the creatine kinase and myoglobin increases (5- to 6-fold control) were more pronounced than BUN levels (2- to 3-fold control).…”

Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

“…However, this is very likely due to hyperthermia since very high doses have been reported not to produce histopathology when conducted under normothermic conditions. When histopathology and adverse liver enzyme changes present in blood serum are compared, EIH and neurotoxic exposures to AMPH have similar adverse effects 103,109 . Furthermore, liver necrosis is not necessary for either dopamine terminal damage or neurodegeneration but lesser perturbations in liver function still may exacerbate such processes 103 .…”

Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

“…When histopathology and adverse liver enzyme changes present in blood serum are compared, EIH and neurotoxic exposures to AMPH have similar adverse effects 103,109 . Furthermore, liver necrosis is not necessary for either dopamine terminal damage or neurodegeneration but lesser perturbations in liver function still may exacerbate such processes 103 . Finally, although AMPH can significantly elevate liver-specific alanine transaminase, and ammonia, in some strains of Sprague-Dawley rats, 108 it minimally elevates this enzyme in other strains when AMPH produces neurotoxicity 103 .…”

Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

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Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity

Bowyer

Hanig

2014

Temperature

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The adverse effects of amphetamine- (AMPH) and methamphetamine- (METH) induced hyperthermia on vasculature, peripheral organs and peripheral immune system are discussed. Hyperthermia alone does not produce amphetamine-like neurotoxicity but AMPH and METH exposures that do not produce hyperthermia (≥40°C) are minimally neurotoxic. Hyperthermia likely enhances AMPH and METH neurotoxicity directly through disruption of protein function, ion channels and enhanced ROS production. Forebrain neurotoxicity can also be indirectly influenced through the effects of AMPH- and METH- induced hyperthermia on vasculature. The hyperthermia and the hypertension produced by high doses amphetamines are a primary cause of transient breakdowns in the blood-brain barrier (BBB) resulting in concomitant regional neurodegeneration and neuroinflammation in laboratory animals. This BBB breakdown can occur in the amygdala, thalamus, striatum, sensory and motor cortex and hippocampus. Under these conditions, repetitive seizures greatly enhance neurodegeneration in hippocampus, thalamus and amygdala. Even when the BBB is less disrupted, AMPH- or METH- induced hyperthermia effects on brain vasculature may play a role in neurotoxicity. In this case, striatal and cortical vascular function are adversely affected, and even greater ROS, immune and damage responses are seen in the meninges and cortical surface vasculature. Finally, muscle and liver damage and elevated cytokines in blood can result when amphetamines produce hyperthermia. Proteins, from damaged muscle may activate the peripheral immune system and exacerbate liver damage. Liver damage can further increase cytokine levels, immune system activation and increase ammonia levels. These effects could potentially enhance vascular damage and neurotoxicity.

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Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

Section: Indirect Adverse Effects On Vasculature Due To the Muscle Lmentioning

confidence: 99%

See 3 more Smart Citations

Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity

Bowyer

Hanig

2014

Temperature

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Microglial activation and vascular responses that are associated with early thalamic neurodegeneration resulting from thiamine deficiency

et al. 2018

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Corticosterone and exogenous glucose alter blood glucose levels, neurotoxicity, and vascular toxicity produced by methamphetamine

Bowyer

Tranter

Sarkar

et al. 2017

Journal of Neurochemistry

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Our previous studies have raised the possibility that altered blood glucose levels may influence and/or be predictive of methamphetamine (METH) neurotoxicity. This study evaluated the effects of exogenous glucose and corticosterone (CORT) pretreatment alone or in combination with METH on blood glucose levels and the neural and vascular toxicity produced. METH exposure consisted of four sequential injections of 5, 7.5, 10, and 10 mg/kg (2h between injections) D-METH. The three groups given METH in combination with saline, glucose (METH+Glucose), or CORT (METH+CORT) had significantly higher glucose levels compared to the corresponding treatment groups without METH except at 3 h after the last injection. At this last time point, the METH and METH+Glucose groups had lower levels than the non-METH groups, while the METH+CORT group did not. CORT alone or glucose alone did not significantly increase blood glucose. Mortality rates for the METH+CORT (40%) and METH+Glucose (44%) groups were substantially higher than the METH (< 10%) group. Additionally, METH+CORT significantly increased neurodegeneration above all other treatments (≈ 2.5-fold in the parietal cortex). Thus, maintaining elevated levels of glucose during METH exposure increases lethality and may exacerbate neurodegeneration. Neuroinflammation, specifically microglial activation, was associated with degenerating neurons in the parietal cortex and thalamus after METH exposure. The activated microglia in the parietal cortex were surrounding vasculature in most cases and the extent of microglial activation was exacerbated by CORT pretreatment. Our findings implicate elevated blood levels of glucose and hyperthermia in METH-induced neurotoxicity, neurovascular damage, and lethality, and that acute elevation of CORT exacerbates both neurotoxicity and neuroinflammation.

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Serum myoglobin, but not lipopolysaccharides, is predictive of AMPH-induced striatal neurotoxicity

Cited by 6 publications

References 49 publications

Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity

Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity

Microglial activation and vascular responses that are associated with early thalamic neurodegeneration resulting from thiamine deficiency

Corticosterone and exogenous glucose alter blood glucose levels, neurotoxicity, and vascular toxicity produced by methamphetamine

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