Hypoxic-ischaemic brain damage in immature rats: effects of adrenoceptor modulation

The purpose of the present study was to evaluate the role of adrenergic receptors in the cascade leading to hypoxic–ischaemic brain injury in neonatal rats. The effect of adrenergic agents (prazosin, yohimbine, idazoxan and clonidine) administered before or after hypoxia–ischaemia was evaluated with respect to mortality and brain injury. Rat pups of either 7 or 8 days of age were subjected to unilateral carotid artery ligation combined with hypoxia (6% or 8% O2in N2). The mortality was higher in hypoxic–ischaemic groups pre-treated with the α-adrenergic receptor antagonists prazosin (48%) or yohimbine (53%) than in saline controls (7%). After 2 weeks the severity of the brain injury was evaluated in the surviving rats. Unilateral brain injury, evaluated by brain weight deficit of the injured ipsilateral hemisphere compared with the contralateral hemisphere, was 17.8±4.9% and 27.1±4.0% in pre- and post-treated saline groups, respectively. Post-treatment with clonidine, an α2-adrenergic agonist, reduced brain injury by 45% (p<0.05) compared with saline controls. Pre-treatment with the same drug was not effective. Idazoxan had no effect on brain injury in this animal model. The results indicate that activation of central α2-adrenergic or imidazole receptors provides neuroprotection during reperfusion after hypoxic–ischaemic brain injury in neonatal rats.