Effective suppression of hippocampal seizures in rats by direct hippocampal cooling with a Peltier chip

Tanaka, Nobuhiro; Fujii, Masami; Imoto, Hirochika; Uchiyama, Joji; Nakano, Kimihiko; Nomura, Sadahiro; Fujisawa, Hironori; Kunitsugu, Ichiro; Saito, Takashi; Suzuki, Michiyasu

doi:10.3171/jns/2008/108/4/0791

Cited by 35 publications

(29 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 This group then showed that they could cool deep into the rat hippocampus by attaching an insulated needle to a Peltier device held away from the brain surface. 28 A limited set of unpublished observations on a single monkey have verified that our thermoelectric device is capable of inhibiting function in the primate neocortex. When our thermoelectric device was placed in direct contact with the pia on the surface of the hand region of the pre-central gyrus, there was a consistent, reversible impairment in skilled finger movements associated with a reduction in surface temperature.…”

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

confidence: 77%

The Therapeutic Potential of Focal Cooling for Neocortical Epilepsy

Rothman

2009

Neurotherapeutics

View full text Add to dashboard Cite

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.

show abstract

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

confidence: 77%

The Therapeutic Potential of Focal Cooling for Neocortical Epilepsy

Rothman

2009

Neurotherapeutics

View full text Add to dashboard Cite

show abstract

“…It is necessary to differentiate this prediction of a retrograde gradient from the shown anterograde preservation of working memory capacity following MTL damage encompassing the hippocampus (Jeneson et al, 2010; Jeneson and Squire, 2012). To the authors knowledge, a retrograde preservation of active working memory traces has not been shown before and constitutes a testable prediction, given neurophysiological deactivation of hippocampal function on the timescale of working memory, such as focal cooling may allow (Tanaka et al, 2008). Experimental lesion studies (Squire and Cohen, 1979; Winocur, 1990; Zola-Morgan and Squire, 1990; Kim and Fanselow, 1992) simply cannot account for the fleeting storage of new percepts in short-term memory.…”

Section: Discussionmentioning

confidence: 96%

Memory consolidation from seconds to weeks: a three-stage neural network model with autonomous reinstatement dynamics

Fiebig

Lansner

2014

Front. Comput. Neurosci.

View full text Add to dashboard Cite

Declarative long-term memories are not created in an instant. Gradual stabilization and temporally shifting dependence of acquired declarative memories in different brain regions—called systems consolidation—can be tracked in time by lesion experiments. The observation of temporally graded retrograde amnesia (RA) following hippocampal lesions points to a gradual transfer of memory from hippocampus to neocortical long-term memory. Spontaneous reactivations of hippocampal memories, as observed in place cell reactivations during slow-wave-sleep, are supposed to drive neocortical reinstatements and facilitate this process. We propose a functional neural network implementation of these ideas and furthermore suggest an extended three-state framework that includes the prefrontal cortex (PFC). It bridges the temporal chasm between working memory percepts on the scale of seconds and consolidated long-term memory on the scale of weeks or months. We show that our three-stage model can autonomously produce the necessary stochastic reactivation dynamics for successful episodic memory consolidation. The resulting learning system is shown to exhibit classical memory effects seen in experimental studies, such as retrograde and anterograde amnesia (AA) after simulated hippocampal lesioning; furthermore the model reproduces peculiar biological findings on memory modulation, such as retrograde facilitation of memory after suppressed acquisition of new long-term memories—similar to the effects of benzodiazepines on memory.

show abstract

“…21) Encouraged by these studies, our group has begun to examine the practicality of focal brain cooling as a therapy for patients with intractable epilepsy. 14,27) …”

Section: History Of Brain Cooling As a Therapy For Epilepsymentioning

confidence: 99%

“…27) The cooling needle, which was attached to the Peltier chip, a thermocouple, and a needle electrode for EEG recording were inserted into the right hippocampus. KA was injected into the left hippocampus to provoke EDs.…”

Section: Hippocampal Seizure Modelmentioning

confidence: 99%

“…35,38) Our institutions have obtained valuable results for the practical use as a new therapy for patients with intractable epilepsy. 14,27) This review describes the effect of focal cooling on seizures, the influence of focal cooling on the normal brain, the mechanisms of seizure termination due to cooling, and the practicality of an implantable cooling system based on our findings and published data.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Application of Focal Cerebral Cooling for the Treatment of Intractable Epilepsy

Fujii

Fujioka

Oku

et al. 2010

Neurol. Med. Chir.(Tokyo)

Self Cite

View full text Add to dashboard Cite

Epilepsy is usually treated with medication, but adequate seizure control is still not achieved in over 30% of epilepsy patients, even with the best available agents. Surgical treatment is also performed for such patients, but is not always successful. Focal cooling of the brain using a thermoelectric device has recently been evaluated as an alternative to epilepsy surgery. Brain cooling was first proposed approximately 50 years ago as an effective method for suppressing epileptic discharges (EDs). Recent studies indicate that focal cooling of the brain to a cortical surface temperature of 209 C to 259 C terminates EDs without inducing irreversible neurophysiological dysfunctions or neuronal damage in the brain tissue. Several mechanisms have been proposed for the antiepileptic effects of focal cooling, including reduction in neurotransmitter release, alternation of activation-inactivation kinetics in voltage-gated ion channels, and the slowing of catabolic processes. Developments in the implantable cooling device with closed-loop cooling systems for seizure detection and focal cooling have been promoted in the field of neuromodulation, but several aspects remain uncharacterized concerning the hardware. Recent advances in precision devices have enabled the optimization of the implantable local cooling system, which may become clinically applicable in the near future.

show abstract

Effective suppression of hippocampal seizures in rats by direct hippocampal cooling with a Peltier chip

Cited by 35 publications

References 34 publications

The Therapeutic Potential of Focal Cooling for Neocortical Epilepsy

The Therapeutic Potential of Focal Cooling for Neocortical Epilepsy

Memory consolidation from seconds to weeks: a three-stage neural network model with autonomous reinstatement dynamics

Application of Focal Cerebral Cooling for the Treatment of Intractable Epilepsy

Contact Info

Product

Resources

About