Is neuronal injury caused by hypoglycemic coma of the necrotic or apoptotic type?
In this study, we explored if a 30 minute period of hypoglycemic coma yields damage which shows some features associated with apoptosis. To that end, we induced insulin-hypoglycemic coma of 30 min duration, and studied brain tissues after the coma period, and after recovery period of 30 min, 3 h, and 6 h. Histopathological data confirmed neuronal damage in all of the vulnerable neuronal populations. Release of cytochrome c (cyt c), assessed by Western Blot, was observed in the neocortex and caudoputamen after 3 and 6 h of recovery. In these regions, the caspase-like activity increased above control after 6 h of recovery. By laser-scanning confocal microscopy, a clear expression of Bax was observed after 30 min of coma in the superficial layers of the neocortex, reaching a peak after 30 min of recovery. Punctuate immunolabeling surrounding nuclei in soma and dendrites in cortical pyramidal neurons likely represents mitochondria, which suggests that Bax protein assembled at the surface of mitochondria in vulnerable neocortical neurons. It is concluded that although previous morphological data have suggested that cells die by necrosis, neuronal damage after hypoglycemic coma shows some features of apoptosis.
Ouyang
Y B
YB
Center for the Study of Neurological Disease, The Queen's Medical Center, Honolulu, Hawaii 96813, USA. yibing@cns.queens.org
He
Q P
QP
Li
P A
PA
Janelidze
S
S
Wang
G X
GX
Siesjö
B K
BK
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D003574:Cytochrome c Group / Q000032:analysis; D004569:Electroencephalography; D007003:Hypoglycemia / Q000473:pathology* / Q000503:physiopathology; D007331:Insulin Coma / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D003574:Cytochrome c Group; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases