A modified double injection model of cisterna magna for the study of delayed cerebral vasospasm following subarachnoid hemorrhage in rats

Delayed cerebral vasospasm is still one of the leading causes of morbidity and mortality in patients suffering from SAH [1,2]. For the development of preventive or therapeutic strategies, intensive research efforts deploying numerous experimental SAH models have been done in the last decades. In 1968, Brawley first described a biphasic cerebral vasoconstriction with an acute and late response following SAH in dogs [3]. Subsequently, different SAH models have been developed in various animal species. However, due to animal rights and cost issues, rats have been increasingly used for the study of vasospasm following SAH in last years [4-7]. The commonly used techniques to induce SAH in rats include: 1) endovascular perforation of the internal carotid artery; and 2) injection of autologous blood into the cisterna magna or prechiasmatic cistern. Endovascular perforation of internal carotid artery causes acute pathophysiological changes resembling most closely aneurysmal rupture in humans [4-7]. However, due to the high mortality rate in the first 24 hours neither the endovascular perforation nor the prechiasmatic injection models are well suitable to study the delayed cerebral vasospasm following SAH. Therefore, the cisterna magna model has been used frequently. The great advantages of this latter model are its simplicity and low mortality rate [8]. Based on the observation that the severity of cerebral vasospasm is exponentially related to the subarachnoid blood volume [9], several studies using double hemorrhage injection model of cisterna magna have recently been performed. The second blood injection 24 or 48 h after the first SAH induction, however, might easily injure the brainstem resulting in high morbidity and mortality. To avoid this pitfall, a modified double hemorrhage rat model employing a catheter has been developed [8]. Here the modified SAH model is described in detail and compared with other double hemorrhage rat models.1. Isoflurane (2-chloro-2-(difluor