PROTECTIVE EFFECT OF MILD HYPOTHERMIA
ON HYPOXIA-ISCHEMIC BRAIN DAMAGE
Jiang Chunming, Mi Yan
The First Hospital of Harbin Medical
University, Harbin, China
Objectives: The aim of this study is to examine the
protective effect of mild hypothermia on hypoxia-ischemic brain damage
(HIBD) in the neonate and to define the optimal therapeutic window of
hypothermia.
Methods: The HIBD model was produced in the traditional
model of neonatal hypoxia-ischemic (HI) which subjected 7-old-day Wistar
rats to unilateral carotid artery ligation followed by an hypoxic (8%
oxyger) episode of 2 hours duration. The rats were divided into five groups
randomly. GroupⅠ: sham-operated. GroupⅡ:No treatment was applied to animal after hypoxic-ischemic onset.
Group Ⅲ:4 hours of hypothermia was applied to animal at
30 minutes after the hypoxic-ischemic onset. Group Ⅳ:hypothermia was applied at 1 hours after hypoxic-ischemic onset.
Group Ⅴ:hypothermia was applied at 3 hours after the
hypoxic-ischemic onset. The homogenate of cortical cells was used to
determine malonyldialdehyde (MDA) content and superoxide dismutase (SOD)
activities. Apoptosis neuronal cell was observed by terminal
deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling(TUNEL)
staining and bax gene expressing.
Results: The MDA content was 170.25 ± 17.00; 325.78 ±
10.77; 244.02 ± 17.07; 298.95 ± 14.74; 312.22 ± 14.57 (mean ± standard
error of the mean, n = 15 per group) for Ⅰ.Ⅱ.Ⅲ.Ⅳ.Ⅴgroups
respectively. The SOD activities for these five respective groups were
31.69±3.30; 51.23±3.10; 60.63±3.38; 53.47±2.45; 52.22±1.91 (mean ± standard
error of the mean,n = 15 per group). The MDA content of group Ⅲ was significantly lower than groupⅡ.Ⅳ.Ⅴ(p<0.01). The number of apoptosis cell for Ⅱ.Ⅲ.Ⅳgroups was 18.80±1.37; 15.53±0.64; 19.53±0.92
(mean±standard error of the mean,n = 15 per group). The number of the cell
that expressed bax gene was 35.87±1.64; 29.13±1.81;
36.20±1.47(mean±standard error of the mean, n = 15 per group). Contrast
with groupⅡ,apoptosis cell of group Ⅲ was significantly lower(p<0.01), but group Ⅳ has no difference with group Ⅱ,moreover the apoptosis cell of group Ⅳ was higher than group Ⅲ obviously(p<0.01).
Conclusions :These results demonstrated that hypothermia prevented
hypoxic-ischemic brain damage by suppressing the generation of free
radicals and the apoptosis of cells; the optimal therapeutic window of mild
hypothermia was within the 30 minutes after the onset of hypoxic-ischemic.