A novel brain trauma model in the mouse: effects of dexamethasone treatment

Abstract

We describe a novel methodological approach for inducing cold lesion in the mouse as a model of human cortical contusion trauma. To validate its reproducibility and reliability, dexamethasone (Dxm) was repeatedly applied to demonstrate possible antioedematous drug effects. Following the induction of anaesthesia with halothane, the dura was exposed via trephination. Using a micromanipulator a pre-cooled (-78 degrees C) copper cylinder, 3 mm in diameter, was pressed down to a depth of 1 mm onto the dura for 30 s under microscopic control. The body temperature was held constant at 37 degrees C throughout the procedure. Blood pressure (BP), measured by a modified photosensor-monitored tail-cuff method, and acid-base status were not significantly different when analysed before and after cold lesion and prior to sacrifice. However, there was a marginal mixed respiratory and metabolic acidosis. The antioedematous action of Dxm was studied in four standard pre-and post-treatment paradigms: 2x0.5 mg/kg (II), 2x12.5 mg/kg (III) and 4x6.25 mg/kg (IV: 3x pre-, 1x post-treatment: V: 1x pre-, 3x post-treatment). Physiological saline injections served as controls. High doses of Dxm (III-V) significantly attenuated the cold-lesion-induced loss of body mass. Dxm treatment also resulted in a reduction of brain water content (III; P<0.05), and brain swelling (IV; P<0.05) in the lesioned hemisphere, relative to controls. In conclusion, we have characterized a novel cold lesion model in the mouse to mimic traumatic brain injury and the beneficial effect of Dxm treatment on the extent of brain oedema.

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

“…Such a model mimics several pathophysiological characteristics of human focal cortical contusion (Nag, 1996) and produces a reproducible, demarcated lesion to the neocortex that allows evaluation of the efficacy of compounds with a neuroprotective potential (Hortobagyi et al, 2000). The present findings extend previous work by showing that rHuEPO significantly reduces brain injury and improves neurological recovery following traumatic insults (Brines et al, 2000;Lu et al, 2005;Ozturk et al, 2005;Shein et al, 2005;Siren et al, 2006;Verdonck et al, 2007;Yatsiv et al, 2005).…”

Caffeic acid attenuates neuronal damage, astrogliosis and glial scar formation in mouse brain with cryoinjury

“…Moreover, the caffeic acid derivative, CAPE, inhibits cell proliferation of human astrocytoma cells (Kim et al, 1998), and vascular smooth muscle cell proliferation induced by angiotensin II in stroke-prone spontaneously hypertensive rats (Li et al, 2005). To our knowledge, pharmacological interventions for late or chronic changes have been investigated very little although interventions for the early injury have been well investigated (Murakami et al, 1999;Hortobagyi et al, 2000;Gorlach et al, 2001;Flentjar et al, 2002;Sewell et al, 2004;Shin et al, 2005;Turkoglu et al, 2005). Because the glial scar formation in the late phase of brain injury may be a physical and biochemical barrier for the regeneration of axons (Silver and Table 1 Effect of caffeic acid on SOD and MDA production in mouse brain tissue 1 day after cryoinjury Miller, 2004), the effect of caffeic acid may be of benefit for the treatment of brain injury.…”

“…In the late phase, one of the changes is the formation of a glial scar resulting from reactive gliosis (mainly consisting of proliferated astrocytes) (Logan and Berry, 2002), which may be a physical and biochemical barrier for the regeneration of axons (Silver and Miller, 2004). To investigate traumatic brain injury, a number of animal models have been developed, among which cryoinjury (also called as cold injury) is one widely used model (Murakami et al, 1999;Hortobagyi et al, 2000). Cryoinjury can mimic some characteristics of traumatic brain injuries and the related repair responses, such as apoptosis (Flentjar et al, 2002), inflammation (Sewell et al, 2004;Shin et al, 2005), angiogenesis (Nag, 2002), astrocyte proliferation and glial scar formation (Hermann et al, 2004;Hirano et al, 2004;Tada et al, 2004).…”

The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity

“…The cold lesion was made using a copper cylinder (3 mm in diameter) that had been precooled with liquid nitrogen. The metal probe was lowered quickly onto the surface of the intact dura over the parietotemporal cortex under microscopic control and pressed down to a depth of 1 mm for 30 seconds (48).…”