A Model of Parasagittal Controlled Cortical Impact in the Mouse: Cognitive and Histopathologic Effects

Abstract

Controlled cortical impact (CCI), using a pneumatically driven impactor to produce traumatic brain injury, has been characterized previously in both the ferret and in the rat. In the present study, we applied this technique to establish and characterize the CCI model of brain injury in another species, the mouse, evaluating cognitive and histopathologic outcome. In anesthetized (sodium pentobarbital, 65 mg/kg) male C57BL mice, we performed sham treatment (no injury, n = 12) or CCI injury (n = 12) at a velocity of 5.7-6.2 m/sec and depth of 1 mm, using a 3-mm diameter rounded-tip impounder, positioned over the left parietotemporal cortex (parasagittal). At this level of injury, we observed highly significant deficits in memory retention of a Morris water maze task 2 days following injury (p < 0.001). Postmortem histopathologic analysis performed at 48 h following injury revealed substantial cortical tissue loss in the region of impact and selective hippocampal neuronal cell loss in the CA2, CA3, and CA3c regions, using Nissl staining. Analysis of degenerating neurons using modified Gallyas silver staining techniques demonstrated consistent ipsilateral injury of neurons in the cortex adjacent to the impact site and in the dentate gyrus of the ipsilateral hippocampus. Bilateral degeneration was observed at the gray matter-white matter interface along the corpus callosum. Glial fibrillary acidic protein (GFAP) immunohistochemistry revealed extensive reactive gliosis appearing diffusely through the bilateral cortices, hippocampi, and thalami at 48 h postinjury. Breakdown of the blood-brain barrier was demonstrated with antimouse IgG immunohistochemistry, revealing extravasation of endogenous IgG throughout the ipsilateral cortex, hippocampus, and thalamus. These results suggest that this new model of parasagittal CCI in the mouse mimics a number of well-established sequelae observed in previously characterized brain injury models using other rodent species. This mouse model may be a particularly useful experimental tool for comparing behavioral and histopathologic characteristics of traumatic brain injury in wild-type and genetically altered mice.

Acute Plasmalemma Permeability and Protracted Clearance of Injured Cells after Controlled Cortical Impact in Mice

“…Previous studies using CCI in mice reported selective vulnerability to neuronal death in CA3 and the hilar regions, as well as dentate gyrus (Hall et al, 2005;Saatman et al, 2006;Smith et al, 1995). Using a depth of CCI set at 0.6 mm, we also observed robust cellular injury using H&E staining in ipsilateral cortex, CA3 and hilus, and dentate gyrus.…”

“…Propidium iodide labeling appeared in distinct populations of traumatically injured brain cells in regions known to be vulnerable to traumatic cell death (Clark et al, 1997;Colicos et al, 1996;Hannay et al, 1999;Smith et al, 1995), including cortex, CA3, the hilar region, and dentate gyrus, with relative sparing of CA1.…”

Modelos experimentales de traumatismo craneoencefálico

“…El modelo de CCI determina fundamentalmente un área de necrosis focal en la corteza, rodeada de un área edematosa que va creciendo progresivamente, reproduciendo todo el espectro de lesiones cerebrales contusivas en humanos 32,68 . Sin embargo, la alteración neuropatológica es realmente más difusa e incluye además del daño cortical, pérdida de células en hipocampo, giro dentado y tálamo ipsilateral que se puede extender al hemisferio contralateral cuando la intensidad del impacto es mayor 43,48,98 . Otras alteraciones anatomopatológicas asociadas son la lesión axonal a nivel de la sustancia blanca subcortical, cápsula interna, núcleos talámicos y tronco cerebral.…”

Animal models for the study of military-related, blast-induced traumatic brain injury

“…CCI injury is caused by the rapid depression of the dura by a flat-faced, cylindrical piston. Earlier models employed a pneumatically-driven impactor [11][12][13], while a more recently engineered device is electromagneticallyregulated, and reportedly results in better control of load velocity, impact depth, and reproducibility [14]. The Impact One™ Stereotaxic Impactor for CCI from myNeuroLab, for example, uses an electromagnetically-driven impactor.…”