Cerebral ischemia global models

An early in vivo study in the model of global forebrain ischemia in the gerbil showed that a selective agonist of A3AR, IB-MECA, acutely administered 15 min prior to ischemia, impaired post-ischemic blood flow, increased mortality and exacerbated the loss of hippocampal neurons (von Lubitz et al. 1994). IB-MECA administration 20 min prior to transient middle cerebral ischemia also resulted in a significant increase in infarct size(von Lubitz et al. 2001). 

Hossmann KA (1997) Reperfusion of the brain after global ischemia hemodynamic disturbances. Shock 8 95-101 Hossmann K-A (1987) Pathophysiology of cerebral infarction. In Vinken PJ, Bruyn GW, Klawans HL (eds) Handbook of clinical neurology. Elsevier, Amsterdam, pp 107-153 Hossmann K-A (1991) Animal models of cerebral ischemia. 1. 

A number of animal models have been developed to mimic cerebral ischemia experimentally. They can be roughly categorized into global (bilateral arterial occlusion) and focal (unilateral arterial occlusion) cerebral ischemia models. Probably the widest applied method is the middle cerebral artery occlusion (MCAO), performed by transiently blocking the arterial blood flow with a removable thread or... 

In 1987, however, a study by Busto et al. (5) showed that small decreases in brain temperature (as little as 2-5°C below normal brain temperature) conferred a marked protective effect against experimental global cerebral ischemia. This finding, as well as subsequent animal studies that modeled neurodegenerative diseases and CNS injury, led to a resurgence of interest in mild hypothermia as a method of cerebral protection. 

KEY STUDIES OF DELAYED HYPOTHERMIA IN RODENT GLOBAL CEREBRAL ISCHEMIA MODELS... 

It is known from animal models with global ischemia and traumatic brain injury that moderate hypothermia attenuates secondary brain damage by reducing cerebral ischemia and postischemic brain edema and preserving the blood-brainbarrier. Even though hypothermia has potent cerebroprotective effects after experimental focal ischemia, clinical studies on hypothermic therapy after MCA infarction were not available until recently. We performed a pilot study investigating the efficacy, feasibility, and safety of induced moderate hypothermia in the therapy of patients with acute, severe MCA infarction and increased ICP. 

Several murine models support a role for oxidative stress in neuronal degeneration. For example, overexpression of SOD isoenzymes reduces both global and focal ischemic injury in models of traumatic brain injury (58-60). Conversely, targeted deletion of Cu, Zn-SOD and extracellular (EC)-SOD worsens the outcome of focal ischemia (61,62). Recently, an especially intriguing protective effect has been observed in a model of cerebral ischemia using middle cerebral artery occlusion (63-65). Application of the EC-SOD mimic, AEOL10113 (a metalloporphyrin catalytic antioxidant) [manganese(III) maso-tetrakis (A-ethylpyridinium-2-yl) porphyrin],... 

Laminin fAnimal models of HD [55], MDMA injury [76], transient global ischemia [77], brain fet embolism [78], embolic focal cerebral ischemia [79], transient focal cerebral ischemia [80], cerebral ischemia [81], subarachnoid hemorrhage [82], cortical spreading depression [59], aging, and AD [83]... 

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