Introduction
Cerebral ischemic rodent models in mouse and rat are widely used in experimental study but their anatomy of arteries before and after ischemic event are rarely demonstrated. With a microangiography system using monochromatic synchrotron radiation X-rays at SPring-8, a third generation synchrotron radiation facility, we studied two experimental ischemic models; MCA occlusion model rat (permanent focal ischemia) and bilateral ICA occlusion model (chronic forebrain ischemia). We also studied cerebral angiography in mouse in which only the high-spatial-resolution imaging with SPring-8 can demonstrate small vessels.
Methods
Microagiography was performed by retrograde injection of 0. 2 ml contrast media via external carotid artery for imaging of internal carotid artery and 0.4 ml for basilar artery. In MCA occlusion model, microclip was applied on MCA by craniectomy and angiography was performed 3hours after initiation of ischemia (acute), 24, 48 and 72 hours after ischemia induction (n=5). Angiography was repeated in each animal after induction of hypercapnia with arterial blood CO2 at 110–120 mmHg. The diameters of major trunk vessels were then assessed. In forebrain ischemic model, one month after bilateral ICA ligation, angiography of vertebral artery and basilar artery was performed (n=12) and compared with acute occlusion (n=3). In normal mouse, microtube was placed in neck ECA and various volume of contrast medium was injected into ICA.
Results
In MCA occlusion model, occlusion points were identified in all rats but variation of development of MCA branches and collateral vessles were demonstrated. Under hypercapia, distension of ICA was observed in acute and 72 hours after ischemia but distentibility was low in 24 and 48 hours. In bilateral ICA occlusion, dilated ACA and MCA were observed in which contrast medium was filled via well-developed Pcom. In acute ICA occlusion, supuratentital arteries were not demonstrated. In normal mouse, 50 ul of 50 % dilated contrast medium was found to be the best condition to demonstrated ICA, MCA and ACA. The diameter of these major trunks were less than 100 um.
Conclusions
Experimental ischemic model in rats had different distensibility depending on the time after the onset of ischemia that was associated with development collateral vessels. To study acute therapeutic approach such as thrombolysis by tPA using rat experimental model, angiographical evaluation should be considered to reveal the exact mechanism and effective time point of the agents. We also showed feasibility of cerebral angiography in mouse. Using synchrotron radiation X-rays, repeat examination can be achieved and this allows us to study further of cerebral vessels using transgenic mouse (See Figure 1).
