Hypothermia suppresses excitatory synaptic transmission and neuronal death induced by experimental ischemia in spinal ventral horn neurons.
METHODS
Whole-cell patch-clamp recordings were performed from the ventral horn neurons obtained from the rat spinal cord slices.


OBJECTIVE
This study investigated the effects of hypothermia on excitatory synaptic transmission and ischemia-induced neuronal death.


BACKGROUND
Hypothermia has long been recognized as a promising physical strategy against both ischemic and traumatic spinal cord injuries. However, the mechanism of hypothermia-mediated neuroprotective action in the spinal cord is still not fully understood at the single cell level.


METHODS
Whole-cell patch-clamp recordings were performed from ventral horn neurons obtained from the spinal cord slices. Ischemia was simulated by superfusing an oxygen- and glucose-deprived medium [ischemia simulating medium (ISM)].


RESULTS
When the temperature of the superfusing artificial cerebrospinal fluid solution was changed from normothermia (36 degrees C) to hypothermia (32 degrees C, 28 degrees C, and 24 degrees C), the frequency of spontaneous excitatory postsynaptic currents was significantly decreased in a temperature-dependent manner. Surperfusing the ISM generated an agonal inward current which consisted of a slow and subsequent rapid inward current in all of the neurons tested. The latencies of the slow and rapid inward currents after the ISM exposures were significantly longer at hypothermia than at normothermia. Hypothermia decreased the slope of the ISM-induced slow inward current, although it did not affect the slope of the rapid inward current. Moreover, the glutamate receptor antagonists slightly prolonged the latencies of the slow and rapid inward currents that were induced by ISM and significantly decreased their slopes.


CONCLUSIONS
These results suggest that hypothermia reduces the excitatory synaptic activities and ischemic neuronal death in the spinal ventral horn. This finding may help in achieving a better understanding of the mechanisms of hypothermia-mediated neuroprotection in the spinal cord.
Nishi
Hideto
H
Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, Japan.
Nakatsuka
Terumasa
T
Takeda
Daisuke
D
Miyazaki
Nobuyuki
N
Sakanaka
Junya
J
Yamada
Hiroshi
H
Yoshida
Munehito
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D015687:Cell Hypoxia; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D005947:Glucose / Q000172:deficiency; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D010100:Oxygen / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D020760:Spinal Cord Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009435:Synaptic Transmission / Q000187:drug effects; D013696:Temperature; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D005947:Glucose; D010100:Oxygen