PROTECTIVE EFFECT OF MILD HYPOTHERMIA ON
HYPOXIA-ISCHEMIC BRAIN DAMAGE
Jiang Chunming, Mi Yan
The First Hospital of Harbin Medical University,
Harbin, China
Objective: 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 group, 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.