**2. Rodent models of cerebral ischemia**

**MCAO [intra-arterial suture occlusion of the middle cerebral artery (MCA)]:** This model is the most widely accepted and has several advantages in mimicking the human stroke. MCAO was first used by Kozuimi et al. [11] and was further revised using a silicone-coated suture technique to control the premature reperfusion subarachnoid haemorrhage [12, 13]. MCAO technique starts with transecting the external carotid artery and temporarily closing the common carotid artery using the thread knot. The suture is passed into an internal carotid artery to the middle and anterior cerebral arteries' junction through the external carotid artery trunk. The suture is left at the junction for a stipulated time and then removed to produce reperfusion. The typical duration of suture occlusion of the MCA in the rat would be 60 min, 90 min, 120 min and permanent occlusion. In this technique, craniotomy is not required, and it produces occlusion of the cerebral artery similar to that seen in the human stroke. MCAO technique will reduce the cerebral blood flow bilaterally and produce around 12% subarachnoid haemorrhage even after using coated suture [14, 15]. Transection of the external carotid artery affects the function of muscles of mastication that produces difficulty in swallowing. This technique is also associated with inadequate behavioural performance outcome measures [16].

MCAO produces ischemic cell death in the frontal, parietal, temporal, occipital cortex and variable damage in the substantia nigra, cervicomedullary junction, hypothalamus and thalamus [17–19]. Damage to diverse brain region will produce complex sensory, motor, autonomic and cognitive deficits. In suture occlusion of 60 min or more, it will impact the hypothalamus significantly [17, 20].

Hypothalamic ischemia produces a hypothermic response in rats that exist for at least 24 hrs after the animal's recovery. Hypothermia worsens cell death, which *Experimental Animal Models of Cerebral Ischemic Reperfusion Injury DOI: http://dx.doi.org/10.5772/intechopen.97592*

confirms that temperature fluctuations have to be considered the primary reason for ischemic cell death in MCAO [19–21]. In MCAO, the cell death pattern follows with the formation of early infarct in the striatum and the formation of delayed infarct in the dorsolateral cortex in the striatum. Striatum infarcts are necrotic and are highly resistant to neuroprotective agents [22–27]. Cortical infarct formation takes a longer duration to show a high level of programmed cell death when compared to striatal infarction [16, 22, 28, 29].

In MCAO, with reperfusion, the striatum will be remained as the core of the ischemic, whereas the cortex region returns to normal blood flow levels [30]. In MCAO, the striatal infarction is the core region of ischemia and cortical infarction where delayed and progressive cell death occurs. The progressive cell death in the region cortex is due to the delayed release of inflammatory mediator TNF-α (Tumor necrosis factor-α), interleukins-1, neutrophil invasion, cytokines release, COX-2 (Cyclooxygenase) activation and oxidative cell injury [31].

Merits of MCAO:


Demerits of MCAO: [37].

