Brain activity changes in a macaque model of oxaliplatin-induced neuropathic cold hypersensitivity

Nagasaka, Kazuaki; Yamanaka, Kazunori; Ogawa, Shinya; Takamatsu, Hiroyuki; Higo, Noriyuki

doi:10.1038/s41598-017-04677-7

Cited by 31 publications

(38 citation statements)

References 45 publications

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“…Histology. The brain damage caused by the infarcts and the locations of the muscimol injections were confirmed histologically in Nissl-stained brain sections as in our previous studies 21,50 . Tissue preparation was performed as previously described [51][52][53][54] .…”

Section: Infarct Induction and Behavioral Testssupporting

confidence: 56%

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Functional near-infrared-spectroscopy-based measurement of changes in cortical activity in macaques during post-infarct recovery of manual dexterity

Kato

Yamada

Kawaguchi

et al. 2020

Sci Rep

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Because compensatory changes in brain activity underlie functional recovery after brain damage, monitoring of these changes will help to improve rehabilitation effectiveness. Functional nearinfrared spectroscopy (fNIRS) has the potential to measure brain activity in freely moving subjects. We recently established a macaque model of internal capsule infarcts and an fniRS system for use in the monkey brain. Here, we used these systems to study motor recovery in two macaques, for which focal infarcts of different sizes were induced in the posterior limb of the internal capsule. Immediately after the injection, flaccid paralysis was observed in the hand contralateral to the injected hemisphere. Thereafter, dexterous hand movements gradually recovered over months. After movement recovery, task-evoked hemodynamic responses increased in the ventral premotor cortex (PMv). The response in the PMv of the infarcted (i.e., ipsilesional) hemisphere increased in the monkey that had received less damage. In contrast, the PMv of the non-infarcted (contralesional) hemisphere was recruited in the monkey with more damage. A pharmacological inactivation experiment with muscimol suggested the involvement of these areas in dexterous hand movements during recovery. These results indicate that fNIRS can be used to evaluate brain activity changes crucial for functional recovery after brain damage.Neuronal motor systems have the capacity for functional recovery following brain damage such as that induced by stroke, and functional recovery can be enhanced by postlesion rehabilitative training 1,2 . Compensatory activity changes in the brain areas that remain undamaged are thought to underlie functional recovery 1,3-16 . Therefore, it is important to monitor brain activity during rehabilitative training to determine whether the training is actually inducing appropriate brain activity changes. Clinical studies in human stroke patients, as well as experimental studies in animals in which damage is artificially induced in a specific region in the brain, have helped to elucidate the compensatory changes of brain activity that occur during the course of functional recovery 1,7-10,17 .We previously established a macaque model for inducing artificial damage in brain regions involved in the transduction of motor commands 2,18,19 . The motor cortex and corticospinal tract of macaque monkeys are more comparable to those of humans than are those of other animals used in experimental research (see ref. 20 . for review). This motor system homology with that of humans, in combination with the relatively large macaque brain, makes imaging data obtained in macaque monkeys comparable to data obtained in clinical research. Therefore, studying macaque models of brain damage can facilitate the translation of findings to stroke patients.Brain damage related to hand functionality can greatly affect the quality of human life and is therefore an important area of study. Using H 2 15 O-positron emission tomography (PET) scans in macaque monkeys, we previously showe...

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Section: Infarct Induction and Behavioral Testssupporting

confidence: 56%

“…Pharmacological inactivation experiment. The region where hemodynamic responses increased most during functional recovery after the infarcts was inactivated by using muscimol and a procedure similar to that used in our previous studies 21,50 .…”

Section: Infarct Induction and Behavioral Testsmentioning

confidence: 99%

Functional near-infrared-spectroscopy-based measurement of changes in cortical activity in macaques during post-infarct recovery of manual dexterity

Kato

Yamada

Kawaguchi

et al. 2020

Sci Rep

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“…The major side effect of platinum derivatives, such as oxaliplatin, is neurotoxicity causing a severe peripheral neuropathy notable for acute cold hypersensitivity because of impairment in the neuronal sodium channel, impairment in calcium homeostasis and chelation of calcium and magnesium, and certain gene polymorphisms (Argyriou, Polychronopoulos, Iconomou, Chroni, & Kalofonos, ; Lecomte, Landi, Beaune, Laurent‐Puig, & Loriot, ; Mannelli et al, ; Nagasaka, Yamanaka, Ogawa, Takamatsu, & Higo, ; S. B. Park et al, ).…”

Section: Resultsmentioning

confidence: 99%

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs

Mashayekhi‐Sardoo

Mohammadpour

Nomani

et al. 2019

Journal Cellular Physiology

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Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negativelyimpact multiple diverse entities including nerves and vascular structures, insulin-like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP 450 , Mdr 1b and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy-dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed.

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“…A direct measure of pain was used in the current study, but it is possible that other behavioral indications of acute LBP could be obtained from the macaques. A further barrier in understanding the mechanism of LBP and the development of effective treatments is elucidating the relationship between pain-related behaviors and central functioning 24,25) . In vivo neuroimaging has been suggested as an objective method of observing pain by quantification of brain activation with defined stimuli 15) .…”

Section: Discussionmentioning

confidence: 99%

Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study

Ushirozako

Yoshida

Togawa

et al. 2019

Spine Surg Relat Res

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Introduction There is currently a lack of translatable, preclinical models of low back pain (LBP). Chymopapain, a proteolytic enzyme used to treat lumbar intervertebral disc (IVD) herniation, could induce discogenic LBP. The current study developed a behavioral model of discogenic LBP in nonhuman primates. Significant brain activation is observed in clinical LBP. Thus, the current study also sought to define brain activation over time in a macaque with discogenic LBP. Methods Responses to pressure applied to the back at L4/L5 were measured in eight adult male Macaca fasciculata using a pressure algometer. The nucleus pulpous of the IVD between L4 and L5 was aspirated and chymopapain (1 mg/mL) was injected under fluoroscopic guidance (n = 2). In two macaques, the nucleus pulpous was only aspirated. Brain activation in response to pressure applied to the lower back was assessed using a 3.0T magnetic resonance imaging scanner in four macaques before and 1, 3, 9, and 14 days after treatment. Results The mean (±SD) response pressure before treatment was 1.4 ± 0.1 kg. One day after chymopapain treatment, the response pressure decreased to 0.6 ± 0.05 kg (P < 0.01), suggestive of pressure hypersensitivity. Over time, the pressure thresholds following chymopapain treatment gradually returned to normal. Following aspiration only, the response pressure was 1.4 ± 0.05 kg, which was not significantly different from the uninjured controls. There was activation of the secondary somatosensory cortex and insular cortex one and three days after chymopapain treatment; there was no activation following aspiration only. Conclusions Enzymatic treatment of the nucleus pulpous leads to acute LBP and pressure-evoked activation in pain-related brain areas. The current model of discogenic LBP parallels clinical LBP and could be used to further elaborate the mechanism of acute LBP.

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Brain activity changes in a macaque model of oxaliplatin-induced neuropathic cold hypersensitivity

Cited by 31 publications

References 45 publications

Functional near-infrared-spectroscopy-based measurement of changes in cortical activity in macaques during post-infarct recovery of manual dexterity

Functional near-infrared-spectroscopy-based measurement of changes in cortical activity in macaques during post-infarct recovery of manual dexterity

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs

Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study

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