DIY caging apparatus to facilitate chronic and continuous stimulation or recording in an awake rodent

Enam, Syed Faaiz; Kang, Brian; Lyon, Johnathan G.; Bellamkonda, Ravi V.

doi:10.1101/2021.12.16.473031

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…The rats were placed in and attached to a custom cage setup to enable free movement (fig. S8, C to E) ( 36 ). Once switched on, the device was able to bring tissue 1.5 mm from the surface of the probe to 25°C ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Cytostatic hypothermia and its impact on glioblastoma and survival

et al. 2022

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Patients with glioblastoma (GBM) have limited options and require novel approaches to treatment. Here, we studied and deployed nonfreezing “cytostatic” hypothermia to stunt GBM growth. This growth-halting method contrasts with ablative, cryogenic hypothermia that kills both neoplastic and infiltrated healthy tissue. We investigated degrees of hypothermia in vitro and identified a cytostatic window of 20° to 25°C. For some lines, 18 hours/day of cytostatic hypothermia was sufficient to halt division in vitro. Next, we fabricated an experimental tool to test local cytostatic hypothermia in two rodent GBM models. Hypothermia more than doubled median survival, and all rats that successfully received cytostatic hypothermia survived their study period. Unlike targeted therapeutics that are successful in preclinical models but fail in clinical trials, cytostatic hypothermia leverages fundamental physics that influences biology broadly. It is a previously unexplored approach that could provide an additional option to patients with GBM by halting tumor growth.

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Section: Resultsmentioning

confidence: 99%

Cytostatic hypothermia and its impact on glioblastoma and survival

et al. 2022

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“…1D). A mechanistic cause was not elucidated but deeper metabolomic or transcriptomic analyses (35) could help. Our brief examination of cytokine and metabolite production and consumption demonstrated reduced activity at all degrees of hypothermia.…”

Section: Discussionmentioning

confidence: 99%

Cytostatic hypothermia and its impact on glioblastoma and survival

Enam

Kilic

Huang

et al. 2021

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Novel therapeutic approaches are needed for patients with recurrent glioblastoma (GBM) who otherwise have limited options. Hypothermia has been used to cryo-ablate tumor locally, but this is ineffective against infiltrative cells as it damages healthy tissue too. Alternatively, here we developed and deployed local ′cytostatic′ hypothermia to stunt GBM growth. We first investigated three grades of hypothermia in vitro and identified a cytostatic window of 20-25°C. We also determined that 18 h/d of cytostatic hypothermia can be sufficient to prevent growth. Cytostatic hypothermia resulted in cell cycle arrest, reduced metabolite production and consumption, and reduced inflammatory cytokine synthesis. We designed a device to deliver local cytostatic hypothermia in vivo in two rodent models of GBM: utilizing the rat F98 and the human U-87 MG lines. Local hypothermia more than doubled the median survival of F98 bearing rats from 3.9 weeks to 9.7 weeks. Two rats survived through 12 weeks. No loss of U-87 MG bearing rats was observed during their study period of 9 weeks. Additionally, we demonstrated that cytostatic hypothermia is synergistic with chemotherapy in vitro. Interestingly, we also demonstrate that CAR T immunotherapy can function with cytostatic hypothermia. Unlike modern targeted therapeutics, cytostatic hypothermia affects multiple cellular processes simultaneously. Thus, irrespective of the host species (e.g., rodent vs. human), it could slow tumor progression and the evolution of resistance. Our studies show that this approach enhances progression-free survival without chemical interventions. However, it may also provide time and opportunities to use standard concomitant, adjuvant, and novel cytotoxic treatments. For these reasons, local cytostatic hypothermia could be a critical addition to the limited options patients with GBM have.

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DIY caging apparatus to facilitate chronic and continuous stimulation or recording in an awake rodent

Cited by 2 publications

References 10 publications

Cytostatic hypothermia and its impact on glioblastoma and survival

Cytostatic hypothermia and its impact on glioblastoma and survival

Cytostatic hypothermia and its impact on glioblastoma and survival

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