Craniectomy Position Affects Morris Water Maze Performance and Hippocampal Cell Loss after Parasagittal Fluid Percussion

Abstract

Valid and reliable animal models are essential for mechanistic and therapeutic studies of traumatic brain injury (TBI). Therefore, model characterization is a continual and reciprocal process between the experimental laboratory and the clinic. Several excellent experimental models of TBI, including the lateral fluid percussion rat model, are currently in wide use in many neurotrauma laboratories. However, small differences in the position of lateral fluid percussion craniectomy are reported between labs. Additionally, differences in hippocampal cell death have also been reported. Therefore, we hypothesized that small changes in craniectomy position could affect commonly used outcome measures such as vestibulomotor function, Morris water maze (MWM) performance, hippocampal cell loss, and glial fibrillary acidic protein (GFAP) immunoreactivity. Four placements were systematically manipulated: rostral, caudal, medial, and lateral. The medial and caudal placements produced significantly greater impairments in the MWM acquisition task over the lateral and rostral placements. The rostral placement produced diffuse cortical damage but little hippocampal cell loss. In contrast, the medial, lateral, and caudal placements produced more mid-dorsally localized cortical damage and significant cell loss in the CA2/CA3 and hilus ipsilateral to the injury site. Furthermore, reactive astrocytosis was more pronounced in the medial, lateral, and caudal placements than in the rostral placement. All craniectomy position groups had similar durations of traumatic unconsciousness and similar impairment on motor tasks. We conclude that small alterations in craniectomy position produce differences in cognitive performance, hippocampal cell loss, and reactive astrocytosis but not in motor performance nor transient unconsciousness.

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

“…Although a selective downregulation of Nogo-A in hilar neurons cannot be excluded, neuronal cell death in the hilus of the dentate gyrus is a well-known consequence of lateral fluid percussion brain injury (Lowenstein et al, 1992;Hicks et al, 1993;Floyd et al, 2002), likely accounting for the observed changes in Nogo-A expression. In addition, we observed numerous Nogo-A (+) processes in the subgranular layer (SGL) of the dentate gyrus emerging post-injury.…”

Repeated mild traumatic brain injury: potential mechanisms of damage

“…Within experiments, direct force onto the brain imparts highly reproducible focal damage, though changes in craniotomy position translate to variable outcomes between laboratories. 39 In the LFP model, a pendulum strikes a fluid-filled reservoir, and pressure from a fluid-filled bolus is forced into the epidural space, 37,40 The LFP model typically induces focal damage such as hemorrhage and edema at the site of impact, with progressive subcortical cell death, [41][42][43] thereby replicating many structural, pathological, and neurobehavioral features of moderatesevere human TBIs. LFP has been used to model single 44 and repeated mTBI, [45][46][47] by lowering the pendulum height to reduce the pressure pulse and therefore injury severity.…”

Behavioral and Histopathological Alterations Resulting from Mild Fluid Percussion Injury

“…Fluid percussion injury was carried out as described previously. [18][19][20] Briefly, rats were initially anesthetized using 5% isoflurane with a 1:1 N 2 O/O 2 mixture and then maintained with a 2.5% isoflurane with 1:1 N 2 O/O 2 mixture via a face mask. Animals were mounted on the stereotaxic frame, a midline 4.8 mm-diameter craniectomy was carefully made midway between bregma and lambda.…”