Focal brain trauma in the cryogenic lesion model in mice

Traumatic brain injury (TBI) and its sequel represent a major cause of disability and death worldwide [1]. TBI consists of the primary irreversible damage and a multitude of secondary cascades, resulting progressively in tissue degeneration and neurological impairment [2-4]. The outcome of severe cerebral lesion does not solely depend on the primary damage, but on the extent of secondary lesions.Several models of experimental traumatic brain injury have been developed in an attempt to reproduce different aspects of the biomechanical impairments and neurological deficits observed in human head injury. The fluid percussion model produces brain injury by rapid injection of fluid into the closed cranial cavity [5,6]. The controlled cortical impact trauma is induced by using a pneumatic impactor to impact exposed brain with a measurable, controllable impact speed and cortical deformation [7]. In comparison to these two models of focal TBI, the unilateral cryogenic lesion model first described in 1958 by Klatzo [8] induces lesions that are well circumscribed and highly reproducible in size and location. Due to an early damage of the blood brain barrier (BBB), the cryogenic cortical injury leads to vasogenic edema, marked brain swelling, and inflammation. The histological and pathological features of cryogenic lesions share many of the hallmark characteristics of human TBI [9,10]. For example, upregulation of inflammatory cytokine expression is detected by real-time PCR as early as 24 h after cryogenic lesion [11]. The cryogenic lesion model can further be used to study long term neurodegenerative changes similar to late complications of human head injury such as global brain atrophy, cognitive impairment, and behavioural abnormalities [12,13]. Furthermore, cryogenic cortical injury has been shown to lead to late brain atrophy and impairment of spatial memory, two key readout parameters for late consequences of TBI [12]. Yet another advantage of the cryogenic model is its