Development of Phase Change Heat Spreader for Treatment of Intractable Neocortical Epilepsy

Hilderbrand, J. K.; Peterson, G. P.; Rothman, Steven M.

doi:10.1080/01457630601117872

Cited by 14 publications

(5 citation statements)

References 5 publications

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“…Our engineering colleagues have designed a thin, bendable, laminar heat pipe composed of outer layers of copper foil and an inner layer of sintered copper columns sandwiched between two layers of sintered copper. 29 The pipe contains water at low pressure, which vaporizes at the warm end, condenses at the cool end, and is wicked back to the warm end, thereby transferring heat. The mechanical properties of this heat pipe indicate that it should be capable of diffusing sufficient heat from a thermoelectric device in contact with the cortex to maintain a cold side temperature of 20°C without heating the adjacent brain above 38°C.…”

Section: ™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™mentioning

confidence: 99%

The Therapeutic Potential of Focal Cooling for Neocortical Epilepsy

Rothman

2009

Neurotherapeutics

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Summary:The therapy of the focal cortical epilepsies remains unsatisfactory. Close to a third of patients fail to gain adequate control with antiepileptic drugs and a portion of those who do, experience unacceptable side effects. Morever, the favorable response rate after surgical resection, approximately 60%, is not nearly as high as the response rate of complex partial seizures caused by mesial temporal sclerosis. The suppressive effect of cooling on neuronal activity has been recognized for over a century. Therefore, we have begun to explore the possible application of cooling as a therapy for focal cortical seizures. In initial brain slice experiments, we found that cooling to 20°C could rapidly terminate paroxysmal activity. Then we developed an in vivo model of focal seizures using a local injection of the convulsant 4-aminopyridine and found that cooling the injected area to less than 24°C with a thermoelectric Peltier device aborted seizures within a few seconds. Other laboratories have independently confirmed our initial observations. More recent experiments from our laboratory have shown that cooling, per se, is not associated with significant cortical damage, even at surface temperatures as low as 5°C. Advances in the fabrication of extremely thin thermoelectric devices, less than a few hundred microns thick, has raised the possibility of incorporating an implantable cooling unit into a closed loop seizure detection and treatment system.

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Section: ™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™mentioning

confidence: 99%

The Therapeutic Potential of Focal Cooling for Neocortical Epilepsy

Rothman

2009

Neurotherapeutics

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“…1). A heat pipe could be used to dissipate the temperature gradient between LED and dura (Hilderbrand et al., 2007). We saw only a tiny rise in slice temperature caused by UV illumination per se, so we would anticipate that robust blood flow would prevent any temperature rise in brain (Sukstanskii & Yablonskiy, 2004).…”

Section: Discussionmentioning

confidence: 99%

Optical suppression of experimental seizures in rat brain slices

et al. 2009

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SUMMARYPurpose: To determine if a small ultraviolet emitting diode (UV LED) could release sufficient c-aminobutyric acid (GABA) from a caged precursor to suppress paroxysmal activity in rat brain slices. Methods: Electrophysiologic recordings were obtained from rat brain slices bathed with caged GABA: 4-[[(2H-benzopyran-2-one-7-amino-4-methoxy)carbonyl]amino]butanoicacid(BC204), atconcentrationsbetween3and30 lM.Seizure-like activity was induced by perfusing slices with extracellular medium lacking magnesium and containing 4-aminopyridine (4-AP; 100 lM). A small, high-power UV LED was used to uncage BC204 and determine whether an increase in ambient GABA could alter normal or paroxysmal activity in the slice. Results: UV LED illumination, in the absence of BC204, had no effect on CA1 population spikes or seizure-like activity. The light did induce a small temperature elevation (<0.15°C) over the current intensities and exposure durations used in these experiments. In the presence of BC204, UV light decreased the CA1 population spike and seizurelike activity. The BC204 effect can be best accounted for by release of GABA: The reduction of population spikes and seizure-like activity was blocked by the GABA antagonist picrotoxin, and BC204 illumination produced a membrane polarization that reversed at the expected potential for GABA A receptors. Discussion: These experiments establish that illumination of a low concentration of caged GABA with a tiny UV LED can release sufficient GABA to attenuate seizure-like activity in brain slices. Because our seizure model is very severe, it is probable that this technique would have a robust effect in human focal epilepsy.

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“…In animals, there has been significant progress made in developing small thermoelectric devices capable of delivering the necessary cooling for the necessary amount of time, displacing corresponding heat, measuring temperature and EEG, and remaining implanted without long term damage to the host . In humans, these device barriers must still be addressed, but investigations continue to deliver promising results …”

Section: Challenge 3: Cooling Systemmentioning

confidence: 99%