Subtalamotomía como neuroprotección en la enfermedad de Parkinson. El papel de los ultrasonidos guiados por resonancia como cirugía temprana

Guridi, Jorge; Marigil, Miguel; Becerra, Victoria; Parras, Olga

doi:10.1016/j.neucir.2016.02.006

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…This phenomenon was not much evident in the late stages of disease progression in the model which is consistent with the standard clinical understanding that the neuroprotective effect of subthalamotomy in advanced PD is not quite successful (Guridi and Obeso, 2015). Early treatment with subthalamotomy in PD can have a neuroprotective effect (Guridi et al, 2016) a trend that was reflected in our computational study. Another factor underlying the neuroprotective effect of subthalamotomy during the early stage of PD is the involvement of presymptomatic compensation mechanisms (Bezard et al, 2003).…”

Section: Discussionsupporting

confidence: 79%

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A Computational Model of Loss of Dopaminergic Cells in Parkinson's Disease Due to Glutamate-Induced Excitotoxicity

Muddapu

Mandali

Chakravarthy

et al. 2019

Front. Neural Circuits

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Parkinson's disease (PD) is a neurodegenerative disease associated with progressive and inexorable loss of dopaminergic cells in Substantia Nigra pars compacta (SNc). Although many mechanisms have been suggested, a decisive root cause of this cell loss is unknown. A couple of the proposed mechanisms, however, show potential for the development of a novel line of PD therapeutics. One of these mechanisms is the peculiar metabolic vulnerability of SNc cells compared to other dopaminergic clusters; the other is the SubThalamic Nucleus (STN)-induced excitotoxicity in SNc. To investigate the latter hypothesis computationally, we developed a spiking neuron network-model of SNc-STN-GPe system. In the model, prolonged stimulation of SNc cells by an overactive STN leads to an increase in ‘stress' variable; when the stress in a SNc neuron exceeds a stress threshold, the neuron dies. The model shows that the interaction between SNc and STN involves a positive-feedback due to which, an initial loss of SNc cells that crosses a threshold causes a runaway-effect, leading to an inexorable loss of SNc cells, strongly resembling the process of neurodegeneration. The model further suggests a link between the two aforementioned mechanisms of SNc cell loss. Our simulation results show that the excitotoxic cause of SNc cell loss might initiate by weak-excitotoxicity mediated by energy deficit, followed by strong-excitotoxicity, mediated by a disinhibited STN. A variety of conventional therapies were simulated to test their efficacy in slowing down SNc cell loss. Among them, glutamate inhibition, dopamine restoration, subthalamotomy and deep brain stimulation showed superior neuroprotective-effects in the proposed model.

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Section: Discussionsupporting

confidence: 79%

“…This excess excitatory drive from STN eventually leads to excitotoxicity in SNc neurons. To overcome this excitotoxicity, subthalamotomy had to be applied very early after diagnosis of PD to have any neuroprotective effect (Guridi et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

A Computational Model of Loss of Dopaminergic Cells in Parkinson's Disease Due to Glutamate-Induced Excitotoxicity

Muddapu

Mandali

Chakravarthy

et al. 2019

Front. Neural Circuits

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The use of nonhuman primate models to understand processes in Parkinson’s disease

et al. 2017

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Research with animal models has led to critical health advances that have saved or improved the lives of millions of human beings. Specifically, nonhuman primate's genetic and anatomo-physiological similarities to humans are especially important for understanding processes like Parkinson's disease, which only occur in humans. Unambiguously, the unique contribution made by nonhuman primate research to our understanding of Parkinson's disease is widely recognized. For example, monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonisms are responsive to dopamine replacement therapies, mimicking what is seen in PD patients. Moreover, groundbreaking neuroanatomical and electrophysiological studies using this monkey model in the 1980s and 1990s enabled researchers to identify the neuronal circuits responsible for the cardinal motor features of PD. This led to the development of subthalamic surgical ablation and deep brain stimulation, the current therapeutic gold standard for neurosurgical treatment. More recently, the mechanisms of α-synuclein spreading testing the prion hypothesis for PD have yielded exciting results. In this review, we discuss and highlight how the findings from nonhuman primate research contribute to our understanding of idiopathic Parkinson's disease.

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Subtalamotomía como neuroprotección en la enfermedad de Parkinson. El papel de los ultrasonidos guiados por resonancia como cirugía temprana

Cited by 2 publications

References 17 publications

A Computational Model of Loss of Dopaminergic Cells in Parkinson's Disease Due to Glutamate-Induced Excitotoxicity

A Computational Model of Loss of Dopaminergic Cells in Parkinson's Disease Due to Glutamate-Induced Excitotoxicity

The use of nonhuman primate models to understand processes in Parkinson’s disease

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