Hypothermic neuroprotection of peripheral nerve of rats from ischaemia-reperfusion injury.
Although there is much information on experimental ischaemic neuropathy, there are only scant data on neuroprotection. We evaluated the effectiveness of hypothermia in protecting peripheral nerve from ischaemia-reperfusion injury using the model of experimental nerve ischaemia. Forty-eight male Sprague-Dawley rats were divided into six groups. We used a ligation-reperfusion model of nerve ischaemia where each of the supplying arteries to the sciatic-tibial nerves of the right hind limb was ligated and the ligatures were released after a predetermined period of ischaemia. The right hind limbs of one group (24 rats) were made ischaemic for 5 h and those of the other group (24 rats) for 3 h. Each group was further divided into three and the limbs were maintained at 37 degrees C (36 degrees C for 5 h of ischaemia) in one, 32 degrees C in the second and 28 degrees C in the third of these groups for the final 2 h of the ischaemic period and an additional 2 h of the reperfusion period. A behavioural score was recorded and nerve electrophysiology of motor and sensory nerves was undertaken 1 week after surgical procedures. At that time, entire sciatic-tibial nerves were harvested and fixed in situ. Four portions of each nerve were examined: proximal sciatic nerve, distal sciatic nerve, mid-tibial nerve and distal tibial nerve. To determine the degree of fibre degeneration, each section was studied by light microscopy, and we estimated an oedema index and a fibre degeneration index. The groups treated at 36-37 degrees C underwent marked fibre degeneration, associated with a reduction in action potential and impairment in behavioural score. The groups treated at 28 degrees C (for both 3 and 5 h) showed significantly less (P < 0.01; ANOVA, Bonferoni post hoc test) reperfusion injury for all indices (behavioural score, electrophysiology and neuropathology), and the groups treated at 32 degrees C had scores intermediate between the groups treated at 36-37 degrees C and 28 degrees C. Our results showed that cooling the limbs dramatically protects the peripheral nerve from ischaemia-reperfusion injury.
Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Y
Y
Mitsui
J D
JD
Schmelzer
P J
PJ
Zollman
M
M
Kihara
P A
PA
Low
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D007036:Hypothermia, Induced; D007511:Ischemia / Q000517:prevention & control*; D008026:Ligation; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology; D009410:Nerve Degeneration / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D012584:Sciatic Nerve / Q000098:blood supply* / Q000473:pathology; D013979:Tibial Nerve / Q000098:blood supply* / Q000473:pathology