Cooling produces minimal neuropathology in neocortex and hippocampus

Yang, Xiaofeng; Kennedy, B.R.; Lomber, Stephen G.; Schmidt, Robert E.; Rothman, Steven M.

doi:10.1016/j.nbd.2006.05.006

Cited by 61 publications

(46 citation statements)

References 27 publications

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“…In addition, no changes were identified in cytochrome oxidase histochemistry. Therefore, in agreement with previous studies, neither the presence of the cryoloops nor their repeated deactivation changed the structure or long-term function of the two cortical areas assayed (Yang et al, 2006). Histological examination revealed that the overwhelming majority of recording sites were in layers IV and V, with lesser numbers of recordings sites in layers III and VI.…”

Section: Effects Of Deactivation On Neuronal Responsesupporting

confidence: 91%

Reciprocal Modulatory Influences between Tonotopic and Nontonotopic Cortical Fields in the Cat

Carrasco

Lomber²

2010

J. Neurosci.

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Functional and anatomical studies suggest that acoustic signals are processed hierarchically in auditory cortex. Although most regions of acoustically responsive cortex are not tonotopically organized, all previous electrophysiological investigations of interfield interactions have only examined tonotopically represented areas. The purpose of the present study was to investigate the functional interactions between tonotopically and nontonotopically organized fields in auditory cortex. We accomplished this goal by examining the bidirectional contributions between the cochleotopically organized primary auditory cortex (A1) and the noncochleotopically organized second auditory field (A2). Multiunit acute recording procedures in combination with reversible cooling deactivation techniques were used in eight mature cats. The synaptic activity of A1 or A2 was suppressed while the neuronal response to tonal stimuli of the noninactivated area (A1 or A2) was measured. Response strength, neuronal threshold, receptive field bandwidths, and latency measures were collected at each recorded site before, during, and after cooling deactivation epochs. Our analysis revealed comparable changes in A1 and A2 neuronal response properties. Specifically, significant decreases in neuronal response strength, increases in neuronal threshold, and shortening of response latency were found in both fields during periods of cooling deactivation. The weak anatomical connections between the two fields investigated make these findings unexpected. Furthermore, the observed neuronal changes suggest a model of corticocortical interaction among auditory fields in which neither differences in the magnitude of anatomical projections nor cortical representation of sensory stimuli are reliable determinants of modulatory functions.

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Section: Effects Of Deactivation On Neuronal Responsesupporting

confidence: 91%

Reciprocal Modulatory Influences between Tonotopic and Nontonotopic Cortical Fields in the Cat

Carrasco

Lomber²

2010

J. Neurosci.

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“…Cooling of the rat brain to 59 C every 2 minutes for 30 seconds for a total duration of 2 hours, and cooling of the cat brain to 39 C for 1-2 hours every day for 7-10 months indicated that the neuropathological consequences of focal brain cooling to 3-59 C were insignificant. 36) These data support our results, and we showed that the threshold temperature at which irreversible neuronal damage was induced was -59 C, not 09 C.…”

Section: Influence Of Focal Cooling On Brain Tissuesupporting

confidence: 91%

Application of Focal Cerebral Cooling for the Treatment of Intractable Epilepsy

Fujii

Fujioka

Oku

et al. 2010

Neurol. Med. Chir.(Tokyo)

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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.

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“…Thus far, we have not seen any evidence that cooling as low as 5°C for 2 hours produces neuronal loss or activates apoptotic pathways. 25 While there is minimal gliosis close to the region of cortical contact with the Peltier, it is similar to the response provoked by any foreign body and cannot be attributed to cooling. Interestingly, when brain slices obtained from transgenic mice expressing the green fluorescent protein (GFP) were cooled to 5°C, there was transient, but completely reversible blebbing of dendrite shafts and loss of spines (FIG.…”

Section: Results With Experimental Epilepsymentioning

confidence: 84%

“…25 These results make us optimistic that the effect of cooling will be exquisitely focal and well tolerated.…”

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

confidence: 98%

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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Cooling produces minimal neuropathology in neocortex and hippocampus

Cited by 61 publications

References 27 publications

Reciprocal Modulatory Influences between Tonotopic and Nontonotopic Cortical Fields in the Cat

Reciprocal Modulatory Influences between Tonotopic and Nontonotopic Cortical Fields in the Cat

Application of Focal Cerebral Cooling for the Treatment of Intractable Epilepsy

The Therapeutic Potential of Focal Cooling for Neocortical Epilepsy

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