J. Dowden et al., Diazepam-induced neuroprotection: dissociating the effects of hypothermia following global ischemia, BRAIN RES, 829(1-2), 1999, pp. 1-6
Global cerebral ischemia produces hippocampal CA1 neuronal loss which in tu
rn leads to deficits in memory related tasks. Previous studies have shown t
hat the benzodiazepine diazepam is effective at attenuating this cell death
and the related behavioural impairments. However these studies have been c
onfounded by diazepam-induced hypothermia. In this study we sought to deter
mine the neuroprotective efficacy of diazepam in the absence of hypothermia
. Diazepam (10 mg/kg) was administered to two groups of gerbils at 30 and 9
0 min following a 5-min ischemic insult. In one group the brain temperature
was monitored for 24 h post-ischemically but not regulated. In the second
group, post-ischemic brain temperature was maintained at 36.5 degrees C to
counteract the hypothermia produced by diazepam. Both behaviour.(open field
performance) and CA1 cell counts from these groups were compared to those
from sham/normal, no drug ischemic and vehicle ischemic groups at 10 days s
urvival. In animals treated with diazepam without temperature regulation, t
here was significant histological and behavioural protection at 10 days com
pared to untreated ischemic animals. Preventing hypothermia in diazepam-tre
ated animals resulted in a decrease in the number of cells surviving (from
41.2 to 31.6% of sham) and abolished behavioural protection. Diazepam appea
rs to have limited ability to attenuate neuronal loss and its neuroprotecti
ve efficacy is augmented by the concurrent hypothermic actions of the drug
itself. (C) 1999 Elsevier Science B.V. All rights reserved.